To explore the effect of tiotropium bromide combined with budesonide formoterol on elderly patients with chronic obstructive pulmonary disease (COPD).

Using the random number table method, the patients with COPD admitted to our hospital from January 2020 to November 2023 were divided into two groups: the control group received conventional treatment and used budesonide formoterol; the other group received the same treatment as the control group plus tiotropium bromide, serving as the experimental group. The blood gas analysis indicators, inflammation-related indicators, quality of life, clinical efficacy, and safety were compared between the two groups.

After treatment, arterial partial pressure of oxygen (PaO₂), generic quality of life inventory 74 (GQOLI-74) scores in the experimental group increased, while partial pressure of carbon dioxide (PaCO₂), interleukin-6 (IL-6), C-reactive protein (CRP) and procalcitonin (PCT) decreased, which were more significant than those in the control group(P<0.05). The experimental group’s overall efficacy rate was 98.33%, significantly better than the control group’s 80.00% (P<0.05). There was no statistically significant difference in adverse reactions between the experimental group (15.00%) and the control group (10.00%) (P>0.05).

Tiotropium bromide in combination with budesonide formoterol can effectively regulate blood gas analysis and the level of inflammation, improve quality of life and enhance clinical efficacy.

Diabetic kidney disease (DKD) is one of the common microvascular complications of diabetes mellitus. Due to its insidious onset and unclear pathogenesis, DKD is easy to progress to end-stage renal disease. Endoplasmic reticulum is the main site of protein synthesis and processing in the body. When affected by adverse factors of the body, endoplasmic reticulum stress (ERS) will be triggered, resulting in the accumulation of misfolded or unfolded proteins, resulting in imbalance of the internal environment. Studies have shown that ERS is involved in the core pathogenesis of DKD, and the renal tissue lesions caused by DKD can be effectively alleviated by regulating ERS. This article focuses on the experimental studies on the intervention of ERS with traditional Chinese medicine and its compound in the prevention and treatment of DKD, in order to provide new ideas and reference for clinical treatment of DKD.

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 establish a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determine the concentration of busulfan in plasma of hematopoietic stem cell transplantation (HSCT) patients and apply it to clinical sample detection.

A Symmetry C₁₈ column 150.0 mm ( 4.6 mm, 3.5 μm) was used. The mobile phase consisted of phase A (10 mmol·L^-1 ammonium formate solution, containing 0.1% formic acid, v/v) and phase B (acetonitrile), and was subjected to gradient elution at a flow rate of 0.8 mL·min^-1, and the injection volume was 10 μL. The internal standard was carbamazepine. The quantitative analysis was ionized with atmospheric pressure chemical ionization source (APCI), positive ion mode, and multi reaction monitoring (MRM). Detecting ion pairs were busulfan 264.4→151.2, carbamazepine 237.1→194.0. The specificity, standard curve, precision, recovery rate, matrix effect and stability of the method were validated.

The retention times of busulfan and internal standard were 5.1 min and 5.3 min, respectively. The standard curve equation for busulfan in plasma was y=0.06x-0.04 (r=0.998 7), with a linear range of 0.1-10.0 μg·mL^-1. The relative standard deviation (RSD) of intra-day and inter-day precision were less than 10%; The recovery rate was 95.64%-104.49%, and the matrix effect was 100.11%-118.87%. The RSD of the stability of quality control samples after low-temperature storage, three freeze-thaw cycles, or room temperature storage were less than 10%. The average drug exposure of patients undergoing HSCT was (4.99±2.76) μg·mL^-1·h (range 0.66-13.77 μg·mL^-1·h).

The established LC-MS/MS method has short analysis time, good specificity, and high precision, and is suitable for the therapeutic drug monitoring of busulfan in HSCT patients.

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.

Based on data mining, network pharmacology and molecular docking technology, we reveal the medication pattern and the molecular mechanism of action of the core pairs of medicines in traditional Chinese medicine (TCM) compounding for the treatment of autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD), and explore the possible effective ways of Chinese medicines for the treatment of co-morbidities of ASD-ADHD. By comparing the pathogenesis of ASD and ADHD and the pharmacological effects of the obtained core pairs, we are searching for the medication ideas of traditional Chinese medicine for the treatment of ASD-ADHD co-occurring disorders.

Microsoft Excel 2016, SPSS Modeler 18.0 and other software were used to perform statistical processing, association analysis, and screening of core drug pairs for the compounded prescriptions that met the inclusion criteria. On the basis of the data mining results, the targets of ASD, ADHD, and the core drug pairs were collected with the help of databases such as TCMSP, GeneCards, etc., and the part of target overlap was regarded as the key target. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the key targets using the databases. Molecular docking of the active ingredients of the core drug pairs with the key targets was performed using AutodockTools 1.5.6 and PyMol 3.1.

A total of 63 herbal prescriptions for ASD and 105 herbal prescriptions for ADHD were screened, and the visualisation network showed that the core pair of medicines for treating both diseases was Acori Tataninowii Rhizoma-Polygalae Radix. Based on the network pharmacology, it was learnt that Acori Tataninowii Rhizoma-Polygalae Radix was able to regulate ASD and ADHD through multiple pathways and targets, and the molecular docking results showed that the main active ingredients in Acori Tataninowii Rhizoma-Polygalae Radix had a good binding affinity with the key targets.

The core drug pairs in the TCM compound formula for treating ASD and ADHD are both Acori Tataninowii Rhizoma-Polygalae Radix, which may play a role in the treatment of co-morbid ASD and ADHD through different mechanisms mediated by different core targets, providing a possible direction for the treatment of co-morbid ASD and ADHD with TCM.

To establish a high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of fluconazole, posaconazole, and linezolid in human cerebrospinal fluid.

Cerebrospinal fluid samples were precipitated with acetonitrile containing internal standard (voriconazole) and separated by Agilent C₁₈ column (2.7 μm, 4.6×150 mm). The mobile phase was 0.1% formic acid aqueous solution acetonitrile, gradient elution, flow rate 0.4 mL·min^-1, column temperature 35 ℃, and injection volume 1μL; The spray ion source, positive ion mode and multi reaction monitoring were used for the determination. The specificity, standard curve, lowerer limit of quantification(LLOQ), precision, accuracy, recovery rate and recovery rate. This method was applied to determine the concentrations of fluconazole, posaconazole, and linezolid in clinical cerebrospinal fluid.

The methodological results showed that fluconazole (0.4-32 μg·mL^-1, r=0.999 6) in cerebrospinal fluid samples, posaconazole (0.04-3.2 μg·mL^-1, r=0.9992) and linezolid (0.2-16 μg·mL^-1, r=0.9989) had a good linear relationship and specificity within the linear range. The LLOQ of, posaconazole, and linezolid was 0.4、0.04 and 0.2 μg·mL^-1, respectively. The relative standard deviation (RSD) values of intra-day and inter-day precision were both less than 15%, with good stability and extraction recovery rates above 80%, unaffected by matrix effects. Additionally, the method exhibited good detection sensitivity for fluconazole, posaconazole, and linezolid in the cerebrospinal fluid of rats and clinical patients. The concentration of the 7 tested sample was within the linear range.

This method is simple, fast, and highly sensitive, and can be used for the determination of cerebrospinal fluid concentrations of fluconazole, posaconazole, and linezolid in clinical patients.

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 observe the clinical efficacy and safety of combination of sintilimab injection and chemotherapy on patients with advanced gastric cancer.

Patients with advanced gastric cancer in gastrointestinal tumor center of the hospital were retrospectively analyzed and divided into control group and treatment group. Control group was given XELOX chemotherapy regimen (intravenous drip of 130 mg·m^-2 oxaliplatin injection on the 1st day of each cycle; oral administration of 1 000 mg·m^-2 capecitabine tablets in the morning and evening, continuous medication from the 1st day to the 14th day of each cycle, 21 days as a cycle). On the basis of control group, treatment group was given 200 mg of sintilimab injection by intravenous drip on the 1st day of each cycle, and were treated no more than 8 cycles (21 days as a cycle), and received maintenance regimen (control group was given single drug treatment, 1 000 mg·m^-2 capecitabine tablets orally in the morning and evening, for 14 consecutive days and 7 days of discontinuation, 21 days as a cycle; on the basis of control group, treatment group was given 200 mg of sintilimab injection, intravenous drip, on the first day of each cycle, 21 days as a cycle) after disease control. The patients were followed up until death. The remission rate, blood markers including matrix metalloproteinase-9 (MMP-9), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and survival prognosis were compared between the two groups, and the safety was evaluated.

A total of 86 patients with advanced gastric cancer were selected from the hospital information system. According to the different treatment regimens, they were classified into control group and treatment group, with 43 cases in each group. After excluding those who changed the drug dose or changed the treatment method due to personal reasons during treatment process, 38 cases were included in control group and 42 cases were included in treatment group. After treatment, the levels of MMP-9 in treatment group and control group were (230.74±54.37) and (311.95±69.76) μg·L^-1, the NLR were 1.44±0.37 and 1.82±0.47, the PLR were 134.42±17.55 and 162.46±17.17, respectively, and there were statistical significantly differences in the above indexes between treatment group and control group (all P<0.05). The objective remission rates in treatment group and control group were 54.76% (23 cases/42 cases) and 31.58% (12 cases /38 cases), and the disease control rates were 96.83% (40 cases/42 cases) and 78.95% (30 cases/38 cases), respectively, the above indicators in treatment group were statistically significantly different from those in control group (all P<0.05). The median progression-free survival [95% confidence interval (CI)] values in treatment group and control group were 19.00 (95%CI: 16.89-21.11) and 12.00 (95%CI: 12.74-17.26) months, and the median overall survival (95%CI) values were 25.00 (95%CI: 23.78-26.22) and 20.00 (95%CI: 16.98-23.02) months, respectively, the above indicators revealed statistical significantly differences between treatment group and control group (all P<0.05). The incidence rates of myelosuppression in treatment group and control group were 45.24% (19 cases/42 cases) and 60.53% (23 cases/38 cases), and the incidence rates of gastrointestinal reaction were 35.71% (15 cases/42 cases) and 39.47% (15 cases/38 cases), and incidence rates of liver function injury were 26.19% (11 cases/42 cases) and 21.05% (8 cases/38 cases), and the incidence rates of hand-foot syndrome were 21.43% (9 cases/42 cases) and 15.79% (6 cases/38 cases), and the incidence rates of neurotoxicity were 40.48% (17 cases/42 cases) and 52.63% (20 cases/38 cases), and the incidence rates of thyroid dysfunction were 7.14% (3 cases/42 cases) and 0.00% (0 cases/38 cases), respectively, without statistical significantly differences (all P>0.05).

The application of sintilimab injection combined with XELOX chemotherapy regimen in patients with advanced gastric cancer can effectively enhance the remission rate, reduce the levels of serum MMP-9, NLR and PLR, and improve the survival prognosis, with good safety.

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.