To observe the clinical efficacy and safety of tacrolimus ointment combined with dupilumab injection in treatment of adult atopic dermatitis (AD).

Adult patients with AD in the Affiliated Hospital of Xuzhou Medical University were enrolled as study subjects. The control group was treated with tacrolimus ointment (external use, twice a day) + ebastine tablets (oral administration, 10 mg·times^-1·d^-1), and the observation group received tacrolimus ointment + ebastine tablets + dupilumab injection (subcutaneous injection, initial dose of 600 mg, followed by 300 mg·times^-1, once every two weeks). The clinical efficacy, skin barrier indicators, serum thymic stromal lymphopoietin (TSLP) and interleukin-31 (IL-31) were compared between the two groups, and the safety was assessed.

A total of 140 cases (80 cases in control group and 60 cases in observation group) were screened in this study. 48 pairs were successfully matched by the propensity matching score method according to the ratio of 1∶1. Finally, 48 cases in control group and 48 cases in observation group were included. After 4 weeks of treatment, the effective rate in observation group was 93.75% (45 cases/48 cases), which was significantly higher than 79.17% (38 cases /48 cases) in control group (P<0.05). the scoring atopic dermatitis (SCORAD) scores in observation and control groups were (15.56±3.33) and (21.50±3.51) points, and the investigator global assessment (IGA) scores were (1.98±0.57) and (2.25±0.44) points, and pruritus index (NRS) scores were (2.85±0.58) and (3.19±0.49) points, and dermatological life quality index (DLQI) scores were (10.04±1.03) and (10.88±1.16) points, and AD disease control (ADCT) scores were (7.00±0.29) and (7.17±0.43) points, respectively. The transdermal water loss (TEWL) values in observation group and control group were (13.17±2.37) g·m^-2·h^-1 and (15.35±3.21) g·m^-2·h^-1, and skin moisture contents were (26.46±4.68)% and (22.23±5.10)%, and sebum contents were (89.79±3.44) μg·cm^-2 and (80.31±3.73) μg·cm^-2, respectively. Serum TSLP levels in observation group and control group were (138.81±14.79) pg·mL^-1 and (148.30±16.23) pg·mL^-1, and serum IL-31 levels were (74.63±9.42) pg·mL^-1 and (85.34±10.18) pg·mL^-1, respectively, and the above indicators in observation group were statistically significantly different compared with those in control group (all P<0.05). During treatment, the adverse drug reactions in observation group were conjunctivitis, edema, diarrhea, swelling and pain at the injection site, and the adverse drug reactions in control group were nausea and edema, and there was no statistical significantly differences in the total incidence rate of adverse drug reactions between groups (P>0.05).

Combination of dupilumab injection on the basis of tacrolimus ointment and ebastine tablets has a significant clinical effect in the treatment of AD, and it can statically significantly improve the symptoms and skin barrier, and reduce the levels of serum TSLP and IL-31.

To observe clinical efficacy and safety of low-dose sitagliptin tablets combined with dapagliflozin tablets in the treatment of elderly patients with diabetic kidney disease (DKD).

According to random number table method, elderly patients with DKD admitted to the hospital were divided into group A (low-dose sitagliptin tables, 50 mg qd), group B (dapagliflozin tables, 10 mg qd) and group C (low-dose sitagliptin tables, 50 mg qd combined with dapagliflozin tables,10 mg qd). All patients were treated for 3 months. The clinical curative effect and changes in fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PG), glycosylated hemoglobin (HbA1c), estimated glomerular filtration rate (eGFR), serum creatinine (SCr), blood urea nitrogen (BUN), uric acid (UA), monocyte chemoattractant protein-1 (MCP-1), adiponectin (APN), nuclear factor-κB (NF-κB) and urinary albumin creatinine ratio (UACR) were compared among the three groups, and the safety evaluation was performed.

In this study, there was no shedding cases. Among the 129 patients, there were 43 cases in group A, 43 cases in group B and 43 cases in group C. After treatment, response rate of group C was 95.35% (41 cases /43 cases), which was significantly higher than that of group A [79.07% (34 cases /43 cases)] and group B [81.40% (35/43 cases)] (all P<0.05). After treatment, HbA1c levels in group A, group B and group C were (7.17±1.21)%, (6.64±1.06)% and (6.13±1.14)%; SCr levels were (94.37±12.16), (86.19±11.45) and (80.45±10.37) μmol·L^-1; and UACR were (80.04±8.36), (71.19±7.72) and (53.04±6.81) mg·g^-1, respectively. Compared with group A, the above indexes were statistically significantly decreased in group B and group C, and which were statistically significantly lower in group C than group B (all P<0.05). After treatment, eGFR in group A, group B and group C were (81.50±9.12), (92.41±9.56) and (103.73±10.24) mL·min^-1 · 1.73 m^-2, respectively. Compared with group A, eGFR was statistically significantly increased in group B and group C, and which was statistically significantly higher in group C than group B (P<0.05). After treatment, MCP-1 levels in group A, group B and group C were (85.38±8.42), (91.40±9.28) and (73.12±8.06) pg·mL^-1; NF-κB levels were (4.09±1.08), (4.71±1.22) and (3.52±0.85) ng·mL^-1, respectively. Compared with group B, the above indexes were statistically significantly decreased in group A and group C, and which were statistically significantly lower in group C than group A (both P<0.05). After treatment, APN levels in group A, group B and group C were (10.17±2.06), (9.15±1.50) and (11.24±2.17) pg·mL^-1, respectively. Compared with group B, APN was statistically significantly increased in group A and group C, and which was statistically significantly higher in group C than group A (P<0.05). The main adverse drug reactions in group A were gastrointestinal discomfort and nasopharyngitis; in group B were gastrointestinal discomfort, hypotension and urinary and reproductive system infection, and in group C were hypoglycemia and gastrointestinal discomfort. There was no significant difference in total incidence of adverse drug reactions among group A, group B and group C (30.23% vs. 20.93% vs. 27.91%, all P>0.05). Pearson correlation analysis showed that decrease of UACR after treatment was positively correlated with the decrease of NF-Κb and MCP-1 and the increase of APN (r=0.419, 0.524, 0.485, all P<0.05).

There is a synergistic effect of low-dose sitagliptin combined with dapagliflozin in the treatment of elderly patients with DKD, which can significantly improve blood glucose metabolism indexes, enhance renal function, regulate levels of inflammatory factors and effectively reduce UACR, with good safety.

To investigate the clinical efficacy of sevelamer combined with Shenshuaining and calcitriol in the treatment of stage 5 chronic kidney disease (CKD) patients complicated with chronic kidney disease-mineral and bone disorder (CKD-MBD).

Patients with stage 5 CKD and CKD-MBD were randomly assigned by a random number table method to the control group (n=54) and the treatment group (n=54). The control group received sevelamer (800 mg per dose, three times daily, taken with meals). On this basis, the treatment group additionally received Shenshuaining oral solution (10 mL per dose, three times daily) and calcitriol (0.25 μg, once daily, orally). The treatment lasted for 12 weeks. The two groups were compared in terms of clinical efficacy, renal function indicators [24-hour urinary total protein (24hUTP), serum creatinine (SCr), and blood urea nitrogen (BUN)], inflammatory cytokines [interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-α (TNF-α)], biochemical indices [intact parathyroid hormone (iPTH)], bone metabolism indices [alkaline phosphatase (ALP) and 25-hydroxyvitamin D (25(OH)D)], and adverse reactions.

A total of 120 patients were screened, and 108 were enrolled (54 in each group). After treatment, the total effective rate was 96.30% (52 cases/54 cases) in the treatment group, higher than 81.48% (44 cases/54 cases) in the control group (P<0.05). After treatment, 24 h UTP, SCr, and BUN levels in the treatment and control groups were (0.83±0.25) vs. (1.32±0.41) g·L^-1; (130.28±29.74) vs. (174.91±34.18) μmol·L^-1; and (9.42±1.94) vs. (12.15±2.61) mmol·L^-1; respectively. IL-6, hs-CRP, and TNF-α levels were (14.32±3.07) vs. (17.61±3.58) ng·L^-1; (3.38±1.14) vs. (6.75±1.63) mg·L^-1; and (16.93±3.15) vs. (21.34±3.81) ng·L^-1, respectively. Serum phosphorus and PTH levels were significantly lower in the treatment group [(1.75±0.37) vs. (2.11±0.42) mmol·L^-1; (101.78±8.68) vs. (125.46±10.73) pg·mL^-1]; while ALP was reduced [(64.31±7.28) vs. (76.45±9.31) IU·L^-1] (all P<0.05). The incidence of adverse drug reactions was 11.11% (6 cases/54 cases) in the treatment group and 7.41% (4 cases/54 cases) in the control group, with no significant difference (P>0.05).

Sevelamer combined with Shen Shuai Ning and Calcitriol significantly improves renal function, bone metabolism, and inflammation in stage 5 CKD patients complicated with CKD-MBD compared to Sevelamer alone, with similar safety and better clinical efficacy.

To investigate the efficacy of bevacizumab combined with 5- fluorouracil+calcium folinate+irinotecan (FOLFIRI) chemotherapy in the treatment of advanced colon cancer and its impact on the vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway.

The patients with advanced colon cancer admitted to our hospital were divided into control group and experimental group according to the random number table method. The control group was given FOLFIRI chemotherapy regimen: on the first day, irinotecan injection 180 mg·m^-2 + 500 mL normal saline was given by intravenous drip ; calcium folinate 400 mg·m^-2 + 250 mL normal saline, intravenous infusion, 2 h infusion completed; fluorouracil injection 400 mg·m^-2, intravenous injection ; fluorouracil 2 400 mg·m^-2,46 h intravenous pumping. The experimental group was treated with bevacizumab on the basis of the control group: after the completion of chemotherapy, bevacizumab 5 mg·kg^-1 + 500 mL normal saline was intravenously administered. Both groups were treated for 2 cycles with 14 days as a cycle. The therapeutic effect, tumor markers [colon cancer specific antigen-2 (CCSA-2 ), carcinoembryonic antigen (CEA), thymidine kinase (TK1), carbohydrate antigen 199 (CA199)], vascular endothelial growth factor (VEGF) / VEGF receptor 2 (VEGFR2) signaling pathway factors, immune function (peripheral blood CD3⁺, CD4⁺, CD8⁺, CD4⁺/CD8⁺), quality of life [cancer treatment function assessment-colorectal cancer scale (FACT-C) score] and adverse reactions were compared between the two groups, and followed up for 1 year, the 1-year survival rate was compared between the two groups.

In this study, 98 patients were screened, all of whom completed the treatment and were followed up for one year. Two patients in the experimental group were lost to follow-up, and one patient in the control group was lost to follow-up. After 2 cycles of treatment, the disease remission rate and disease control rate of the experimental group (55.10%, 69.39%) were higher than those of the control group (34.69%, 44.90%) (P<0.05). After 2 cycles of treatment, the peripheral blood CD3⁺ in the experimental group and the control group were (60.75±3.29)% and (58.81±3.10)%; CD4⁺/CD8⁺ were (1.76±0.40)%, (1.29±0.38)%; CD4⁺ were (38.65±3.05)%, and (33.12±2.86)% ; the serum CEA was (18.71±4.10) and (23.69±3.68) ng·mL^-1; the serum VEGF levels were (236.28±55.79) and (380.44±81.32) pg·mL^-1; the serum CA199 levels were (22.48±4.26) and (37.19±4.55) U·mL^-1; serum VEGFR2 were (1 131.16±142.53) and (1 514.79±215.41) pg·mL ^-1 ; serum TK1 was (1.15±0.23) and (1.92±0.31) pmol·L^-1, the serum CCSA-2 levels were (15.13±3.06) and (19.04±3.25) ng·mL^-1. Peripheral blood CD8⁺ were (22.02±2.15)%, (25.68±2.62)% ; the peripheral blood CD3⁺, CD4⁺/CD8⁺ and CD4⁺ in the experimental group were higher than those in the control group, and the serum CEA, VEGF, CA199, VEGFR2, TK1, CCSA-2 and peripheral blood CD8⁺ were lower than those in the control group (P<0.05). After 2 cycles of treatment, the physical status scores of FACT-C in the experimental group and the control group were (21.35±2.39) and (18.07±3.16) scores; the scores of social / family status were (24.27±1.31) and (20.94±1.75) scores; the scores of emotional status were (18.56±1.81) and (16.17±2.03) scores; the functional status scores were (22.42±1.64) and (19.78±2.18) scores; the specific module scores of colorectal cancer were (30.52±2.18) and (27.16±2.35) scores; the above indexes in the experimental group were higher than those in the control group (P<0.05). The incidence of leukopenia and gastrointestinal reactions in the experimental group (34.69%, 16.33%) was lower than that in the control group (61.22%, 36.73%) (P<0.05). After 1 year of follow-up, the survival rate of the experimental group (80.85%) was higher than that of the control group (62.50%) (P<0.05).

The combination therapy of FOLFIRI chemotherapy and bevacizumab for patients with advanced colon cancer can effectively regulate the VEGF/VEGFR2 signaling pathway, reduce tumor marker levels, improve immune function, decrease the occurrence of adverse reactions, enhance treatment efficacy, improve patients’ quality of life, and increase survival rates.

To investigate the temporal association and molecular mechanism of bortezomib-induced mitochondrial oxidative stress and apoptosis in Schwann cells.

Rat Schwann RSC96 cells were cultured in vitro and treated with different concentrations of bortezomib to establish an in vitro model of bortezomib damaged RSC96 cells. The assessment of cell viability was conducted by means of the CCK-8 method, and the morphological alterations observed in each group of cells were documented through inverted microscope analysis. DCFH-DA and Hoechst staining were combined with fluorescence microscopy to determine the content of reactive oxygen species. JC-1 staining was used to detect mitochondrial membrane potential level, and the degree of mitochondrial permeability transition pore opening and Ca²⁺ concentration were detected by fluorescence microscope. Annexin V-FITC/PI dual labeling was used to detect cell apoptosis. ELISA was used to detect the levels of inflammatory factors TNF-α, IL-1β, and IL-6.

In comparison with the control group, as the bortezomib concentration increased, the viability of RSC96 cells decreased in a concentration-dependent manner. The cell gap increased, the number of cells decreased significantly, the nucleus solidified, and the cells exhibited typical characteristics of apoptosis. Furthermore, bortezomib induced a reactive oxygen species burst in RSC96 cells in a dose-dependent manner, resulting in depolarization of mitochondrial membrane potential, cytosolic Ca²⁺ overload, continuous opening of the mitochondrial permeability transition pore, and a significant increase in the apoptosis rate of RSC96 cells.

Bortezomib has been shown to induce programmed cell death apoptosis in Schwann cells by activating an axis involving oxidative stress, mitochondrial damage, and subsequent apoptosis. This finding suggests that oxidative stress and mitochondrial damage may represent pivotal mechanisms of bortezomib-induced toxicity, thus providing a novel target for the intervention of BIPN.

To investigate the effect of L-carnitine on hypoxic-ischemic brain damage in neonatal mice by regulating PI3K/AKT pathway.

Eighty mice with successful hypoxic-ischemic brain damage models were randomly divided into model group, L-carnitine low-dose group, L-carnitine medium-dose group and L-carnitine high-dose group, with 20 mice in each group, and 20 mice without modeling were used as sham operation group. The mice in the L-carnitine low-dose group, L-carnitine medium-dose group and L-carnitine high-dose group were intraperitoneally injected with L-carnitine at 100, 250 and 500 mg·kg^-1, respectively. The mice in the sham-operation group and the model group were intraperitoneally injected with the same amount of normal saline, the administration lasted for one week. The pathological changes of brain tissue were analyzed by hematoxylin-eosin staining. TCC staining was used to analyze the cerebral infarction area. The apoptosis of neurons in mouse brain tissue was analyzed by in situ terminal assay. The levels of inflammatory factors in brain tissue of mice were detected by enzyme-linked immunosorbent assay. The expression levels of PI3K/AKT pathway-related proteins were detected by Western blotting.

The brain tissue cells of the sham operation group were closely arranged and the structure was intact. In the model group, the brain tissue structure was disordered, a large number of cells were shed, the intercellular space was enlarged, and the morphology was swollen. The brain tissue loss of mice in different L-carnitine dose groups was gradually improved. The cerebral infarction rates in the sham-operated group, the model group, the low-dose L-carnitine group, the middle-dose L-carnitine group, and the high-dose L-carnitine group were (0.83±0.08)%, (59.32±3.12)%, (33.72±1.55)%, (25.58±1.21)%, and (9.81±1.07)%, respectively; the apoptosis rates of neurons were (1.85±0.18)%, (37.31±1.25)%, (21.67±1.02)%, (15.62±2.31)% and (6.63±0.88)%, respectively; the levels of interleukin-6 were (1.32±0.08), (13.21±1.16), (9.33±0.19), (6.03±0.18) and (3.73±0.15) pg·mL^-1, respectively; the levels of tumor necrosis factor α were (2.02±0.15), (15.07±1.26), (10.08±2.06), (7.13±1.16) and (4.06±0.08) pg·mL^-1, respectively; the relative expression levels of PI3K protein were 0.65±0.09, 0.10±0.01, 0.19±0.03, 0.35±0.03 and 0.55±0.06, respectively; the relative AKT protein expression levels were 0.69±0.05, 0.11±0.02, 0.21±0.02, 0.39±0.03 and 0.63±0.06, respectively. Compared with the model group, the above indicators in the L-carnitine low-dose group, the L-carnitine medium-dose group and the L-carnitine high-dose group had statistically significant differences (all P<0.05).

L-carnitine can alleviate hypoxic-ischemic brain damage in neonatal mice, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway.

To investigate the median effective dose (ED₅₀) of ciprofol combined with alfentanil inhibiting responses to gastroscopy in geriatric patients.

A total of 115 elderly patients scheduled for elective painless gastroscopy were enrolled in this study. Patients scheduled for gastroscopy were divided into four groups according to age and gender: Group A consisted of males aged 65-74 years, Group B consisted of females aged 65-74 years, Group C consisted of males aged 75-85 years, and Group D consisted of females aged 75-85 years. Based on the modified Dixon sequential test method, intravenous alfentanil 4 ug·kg^-1 was administered followed by ciprofol, with an initial dose of 0.3 mg·kg^-1 and the injection time was longer than 30 s, and the dose gradient was set at 0.03 mg·kg^-1. The ED₅₀, 95% effective dose (ED₉₅), and their 95% confidence intervals (CIs) for gastroscopic response in the four patient groups were calculated using probit regression analysis. Additionally, vital signs were documented for all groups.

The calculated ED₅₀ and its 95% CI for the dosage of ciprofol in the four groups of elderly patients were 0.19 (0.17-0.21) mg·kg^-1 in group A, 0.20 (0.18-0.22) mg·kg^-1 in group B, 0.15 (0.12-0.18) mg·kg^-1 in group C, 0.17(0.15-0.19) mg·kg^-1 in group D. The ED₉₅ and its 95% CI were 0.23 (0.09-0.32) mg·kg^-1 for Group A, 0.25 (0.23-0.30) mg·kg^-1 for Group B, 0.20 (0.18-0.38) mg·kg^-1 for Group C, and 0.21 (0.19-0.31) mg·kg^-1 for Group D. There was no statistically significant difference in the ED₅₀ of ciprofol between genders within the same age group (P>0.05). However, the ED₅₀ of ciprofol in patients aged 75-85 was significantly lower than that in patients aged 65-74 of the same gender (P<0.05). The Hosmer-Lemeshow test indicated that the Probit models for all four groups fitted well (P>0.05).

The ED₅₀ and its 95% CI for the inhibition of the entry response during painless gastroscopy in elderly patients by ciprofol combined with 4.00 ug·kg^-1 alfentanil were 0.19 (0.17-0.21) mg·kg^-1 in group A, 0.20 (0.18-0.22) mg·kg^-1 in group B, 0.15 (0.12-0.18) mg·kg^-1 in group C, 0.17(0.15-0.19) mg·kg^-1 in group D. Age-stratified dosage adjustment of ciprofol is necessary to minimize adverse reactions.

To characterize the clinical manifestations, virulence factors, and antimicrobial resistance profiles of hypervirulent Klebsiella pneumoniae (hvKp) infections, thereby improving the understanding of hvKp and informing evidence-based strategies for early diagnosis and precise antimicrobial therapy.

A retrospective analysis of 14 patients with hvKp infection admitted to the emergency department of peking university first hospital between April 2021 and May 2023 was performed. Data on clinical characteristics, laboratory results, virulence genes, and antimicrobial susceptibility were collected and analyzed.

All 14 patients with hvKp infections had community-acquired cases, predominantly male (71.43%, 10 cases/14 cases), with a median age of 69 years. Diabetes mellitus was present in 78.57% (11 cases/14 cases) of the patients. Clinical features included varying degrees of liver injury and bacteremia in all cases, with 71.43% (10 cases/14 cases) complicated by liver abscesses, 78.57% (11 cases/14 cases) by pulmonary infections, 57.14% (8 cases/14 cases) by acute kidney injury, 35.71% (5 cases/14 cases) requiring mechanical ventilation, and 35.71% (5 cases/14 cases) resulting in mortality. Laboratory findings showed significantly elevated C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR) levels, which were 150.00~356.00 mg·L^-1and 9.04%~66.97%, respectively. 92.86% (13 cases/14 cases) exhibiting decreased albumin levels upon admission, of which 50% demonstrated a >20% decline by the next day. The string test was positive in 69.23% (9 cases/13 cases) of cases. Virulence and resistance profiling via mNGS on three isolated strains revealed the presence of iutA, iucABD, fimH, and gaLF genes in all isolates, with two (66.67%) carrying rmpA2. Among the 14 isolates, antimicrobial susceptibility testing of 12 hvKp strains indicated high susceptibility to most antibiotics; however, two (14.29%) were identified as multidrug-resistant (MDR) including one extended spectrumβ lactamases (ESBLs) producing strain and one carbapenem resistant carbapenem resistant klebsiella pneumoniae (CRKP) strain.

HvKp infections predominantly affect male patients with diabetes, characterized by liver abscesses leading to metastatic infections at multiple sites, rapid progression, and high mortality. Dynamic monitoring of albumin levels, the string test, and imaging studies facilitate early detection. Although most hvKp strains remain highly susceptible to commonly used antibiotics, vigilance against MDR strains is essential. Enhanced surveillance of high-risk populations and individualized antimicrobial strategies are recommended.

To investigate the effects of andrographolide on microRNA (miR) -218-5p/RY box transcription factor 5 (SOX5) on the proliferation, invasion and epithelial mesenchymal transformation (EMT) of oral squamous cell carcinoma cells.

CAL-27 cells were divided into the following groups: blank group (conventional culture), andrographolide group (treated with 15 μmol·L^-1 andrographolide), andrographolide + inhibitor NC group (treated with 15 μmol·L^-1 andrographolide and transfected with inhibitor NC), andrographolide + miR-218-5p inhibitor group (treated with 15 μmol·L^-1 andrographolide and transfected with miR-218-5p inhibitor), andrographolide + miR-218-5p inhibitor + si-NC group (treated with 15 μmol·L^-1 andrographolide and co-transfected with miR-218-5p inhibitor and si-NC), and andrographolide + miR-218-5p inhibitor + si-SOX5 group (treated with 15 μmol·L^-1 andrographolide and co-transfected with miR-218-5p inhibitor and si-SOX5). The relative expression levels of miR-218-5p and SOX5 mRNA were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), cell proliferation ability was measured using the 5-ethynyl-2′-deoxyuridine (EdU) assay, cell invasion ability was assessed by Transwell assay, and the relative expression levels of EMT-related proteins were determined by Western blotting.

After different treatment periods, the relative expression levels of miR-218-5p in blank group, andrographolide group, andrographolide + inhibitor NC group and andrographolide + miR-218-5p inhibitor group were 1.00±0.11, 2.76±0.48, 2.69±0.50 and 1.19±0.17, respectively; the relative expression levels of SOX5 mRNA were 1.00±0.09, 0.36±0.07, 0.35±0.05 and 0.93±0.18, respectively. Compared with the blank group, the andrographolide group showed statistically significantly upregulated miR-218-5p relative expression levels and statistically significantly reduced SOX5 mRNA relative expression levels (all P<0.05). The proliferation rates in blank group, andrographolide group, andrographolide + inhibitor NC group, andrographolide + miR-218-5p inhibitor group, andrographolide + miR-218-5p inhibitor + si-NC group and andrographolide + miR-218-5p inhibitor + si-SOX5 group were (62.76±8.14)%, (23.58±2.87)%, (25.12±3.64)%, (51.29±9.12)%, (50.76±8.29)% and (34.18±6.83)%, respectively; the number of invasive cells were (154.23±17.24), (67.13±9.37), (72.81±11.28), (125.36±18.74), (118.15±19.80) and (80.44±12.13), respectively; the relative expression levels of E-cadherin were 1.00±0.12, 2.62±0.43, 2.56±0.47, 1.47±0.27, 1.51±0.23 and 2.24±0.43, respectively; the relative expression levels of N-cadherin were 1.00±0.11, 0.41±0.08, 0.39±0.06, 0.83±0.17, 0.86±0.15 and 0.51±0.10, respectively; the relative expression levels of Vimentin were 1.00±0.08, 0.49±0.07, 0.46±0.09, 0.85±0.16, 0.88±0.17 and 0.55±0.11, respectively. Compared with blank group, andrographolide group showed statistically significantly decreased proliferation rate, number of invasive cells and relative expression levels of N-cadherin and Vimentin, while demonstrating statistically significantly increased relative expression levels of E-cadherin (all P<0.05).

Andrographolide inhibits the proliferation, invasion, and EMT in oral squamous cell carcinoma, potentially through upregulating miR-218-5p and subsequently targeting the suppression of SOX5 expression.

To investigate the effects of nintedanib on apoptosis and autophagy of hepatocellular carcinoma cells, and to explore the role of non-receptor type protein tyrosine phosphatase 1(SHP-1) and signal transducer and activator of transcription3 (STAT3).

Hep3B cells were divided into Hep3B group (normal culture), nintedanib group (treated with 10 μmol·L^-1 nintedanib for 48 h), nintedanib+si-NC group (based on the nintedanib group, transfected with si-NC before nintedanib treatment), and nintedanib+si-SHP-1 group (based on the nintedanib group, transfected with si-SHP-1 before nintedanib treatment). Reverse transcription real-time fluorescence quantitative polymerase chain reaction was used to detect SHP-1 messenger RNA (mRNA) levels. Western blot was used to detect the protein levels of SHP-1, B-cell lymphoma-2 (Bcl-2), inhibitor of apoptosis protein-1 (IAP-1), Survivin, Beclin-1, phosphorylated Beclin-1 (p-Beclin-1), STAT3, phosphorylated STAT3 (p-STAT3), Janus kinase 2 (JAK2) and phosphorylated JAK2 (p-JAK2) in cells. Methyl thiazolyl tetrazolium assay was used to detect the cell viability of human liver cancer cells Hep3B after treatment with different concentrations of nintedanib. Immunofluorescence was used to detect the relative expression levels of SHP-1 and microtubule-associated protein 1 light chain 3 (LC3) in cells. TdT mediated dUTP nick end labeling assay was used to detect the apoptosis of Hep3B cells in each group.

The relative expression levels of SHP-1 mRNA in THLE-2, PLC5, HuH7, Hep3B and SK-Hep1 cells were 1.00±0.16, 0.45±0.08, 0.58±0.09, 0.29±0.04 and 0.34±0.06, respectively; the relative expression levels of SHP-1 protein were 1.00±0.13, 0.71±0.09, 0.83±0.12, 0.56±0.07 and 0.79±0.08, respectively. Compared with the THLE-2 group, the differences in the relative expression levels of SHP-1 mRNA and protein in PLC5, HuH7, Hep3B, and SK-Hep1 groups were statistically significant (all P<0.05). The cell viability of human liver cancer cells Hep3B treated with 0, 1, 5, 10, 15 and 20 μmol·L^-1 nintedanib were (100.00±2.39)%, (92.17±16.85)%, (84.63±15.21)%, (59.02±10.74)%, (36.98±7.53)% and (29.34±5.67)%, respectively. Except for 1 μmol·L^-1 group, the differences in Hep3B cell viability between other nintedanib treatment groups and 0 μmol·L^-1 group were statistically significant (all P<0.05). The relative expression levels of SHP-1 mRNA in Hep3B group, nintedanib group, nintedanib+si-NC group, and nintedanib+si-SHP-1 group cells were 1.00±0.19, 3.06±0.57, 2.84±0.52 and 1.58±0.26, respectively; the relative expression levels of SHP-1 protein were 1.00±0.16, 3.07±0.54, 3.48±0.63 and 1.32±0.19, respectively; the apoptosis rates were (19.34±3.16)%, (62.85±10.93)%, (67.49±11.78)% and (24.72±4.29)%, respectively; the relative expression levels of Bcl-2 were 1.00±0.12, 0.56±0.07, 0.63±0.08 and 0.84±0.10, respectively; the relative expression levels of IAP-1 were 1.00±0.15, 0.38±0.06, 0.44±0.07 and 0.71±0.12, respectively; the relative expression levels of Survivin were 1.00±0.14, 0.62±0.09, 0.56±0.08 and 0.83±0.11, respectively; the levels of p-Beclin-1/Beclin-1 were 1.00±0.18, 2.37±0.41, 2.25±0.39 and 1.48±0.26, respectively; the levels of LC3 were 1.00±0.21, 3.74±0.69, 3.15±0.60 and 1.52±0.28, respectively; the levels of p-STAT3/STAT3 were 1.00±0.11, 0.43±0.05, 0.49±0.08 and 0.88±0.10, respectively; the levels of p-JAK2/JAK2 were 1.00±0.15, 0.54±0.07, 0.48±0.07 and 0.79±0.13, respectively. There were statistically significant differences in the above indicators between nintedanib group and Hep3B group, and between nintedanib+si-shp-1 group and nintedanib+Si NC group (all P<0.05).

Nintedanib can induce apoptosis and autophagy of hepatocellular carcinoma cells, which may be realized through SHP-1 mediated STAT3 signaling pathway.