To investigate the effect of Jinfu’an decoction on the apoptosis of non-small cell lung cancer cells (A549) by regulating phosphatidylinositol 3-kinase/ protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway mediated autophagy.

A549 cells were randomly divided into blank group, control group, combined group and experimental -L, -M, -H groups. The blank group was treated with 10% blank serum. The control group was treated with 20 μmol·L^-1 PI3K specific activator (740Y-P). The experimental-L, -M, -H groups were treated with 5%, 10% and 20% Jinfu ’an decoction containing serum, respectively. The combined group was treated with 20% Jinfu ’an decoction serum +20 μmol·L^-1 740Y-P. Flow cytometry was used to detect the apoptosis rate. Western blot was used to detect the expression levels of microtubule-associated protein 1A/1B -light chain 3 (LC3), sequestosome-1 (p62), Akt and mTOR.

The apoptosis rates of experimental -H group, combined group, control group and blank group were (31.48±1.35)%, (14.91±1.26)%, (3.30±0.45)% and (7.73±0.50)%, respectively; the relative expression levels of LC3 Ⅱ/Ⅰ protein were 1.13±0.10, 0.77±0.06, 0.31±0.04 and 0.50±0.04, respectively; the relative expression levels of p62 protein were 0.32±0.03, 0.56±0.05, 1.07±0.06 and 0.83±0.06, respectively; the relative expression levels of p-Akt/Akt protein were 0.33±0.04, 0.80±0.07, 0.98±0.09 and 0.52±0.03, respectively; the relative expression levels of p-mTOR/mTOR protein were 0.53±0.04, 0.84±0.06, 1.14±0.08 and 1.01±0.06, respectively. The above indexes of the experimental -H group were statistically different from those of the combination group and the blank group (all P<0.05).

Jinfu’an decoction can promote the apoptosis of A549 cells, and its mechanism may be related to the inhibition of PI3K/Akt/mTOR signaling pathway and the activation of cell autophagy.

To observe the clinical efficacy and safety of tislelizumab injection in the treatment of patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations and resistance to targeted therapy.

Patients with advanced NSCLC and EGFR mutations were assigned to control group and treatment group. The control group received 500 mg·m^-2 pemetrexed disodium for injection by intravenous infusion on the first day + 7.5 mg·kg^-1 bevacizumab injection by intravenous infusion every 3 weeks + 80 mg·m^-2 nedaplatin by intravenous infusion on the first day. On the basis of control group, the treatment group received 200 mg tislelizumab injection by intravenous infusion every 3 weeks. Two groups were treated for 3 cycles with 3 weeks per cycle. The clinical efficacy, tumor markers, quality of life and safety were compared between two groups.

Treatment group was enrolled 51 cases; control group was enrolled 51 cases. After treatment, the overall effective rates of treatment and control groups were 54.90% (28 cases / 51 cases) and 21.57% (11 cases / 51 cases), with statistically significant difference (P<0.01). After treatment, the levels of carcinoembryonic antigen (CEA) in treatment and control groups were (6.67±1.24) and (11.58±1.36) ng·mL^-1; the levels of cytokeratin-19 fragments were (7.64±1.47) and (12.25±1.63) ng·mL^-1; the levels of neuron-specific enolase were (22.65±2.81) and (25.05±2.94) ng·mL^-1; the quality of life scores were (73.67±6.24) and (64.45±5.36) points; the median progression-free survival were 7.00 and 10.00 months; the median overall survival were 14.00 and 20.00 months, respectively. The differences of above indexes were statistically significant between two groups (all P<0.05). The adverse drug reactions of two groups were nausea and vomiting, liver function impairment and renal function impairment. The incidences of total adverse drug reactions in treatment and control groups were 27.45% (14 cases/51 cases) and 31.37% (16 cases/51 cases), without statistically significant difference (P>0.05).

Tislelizumab injection has a definitive clinical efficacy in the treatment of patients with advanced NSCLC harboring EGFR mutations and resistance to targeted therapy, which can reduce the tumor marker levels, improve the quality of life, with high safety.

To explore the mechanism of long non-coding RNA prostate cancer-associated transcript 19 (LncRNA PCAT19) knockdown on oxaliplatin (OXA) sensitivity of human gastric cancer cells by regulating microRNA (miR)-200c-3p mediated ataxia-telangiectasia mutated proteins (ATM) and Rad3-related kinase-related kinase (ATR) / checkpoint kinase1(CHK1) signaling pathway.

Human gastric adenocarcinoma cells (AGS) were randomly divided into OXA group (8 μg·L^-1 OXA), OXA+si-NC+inh-NC group (si-NC and inh-NC co-transfected with +8 μg·L^-1 OXA), OXA+si-PCAT19+ inh-NC group (si-PCAT19 and inh-NC co-transfected +8 μg·L^-1 OXA), OXA+si-PCAT19+ miR-200c-3p inh group (si-PCAT19 and miR-200c-3p inh co-transfected +8 μg·L^-1 OXA). Cell proliferation in each group was detected by 5-acetylidene-2′-deoxyuridine assay; cell apoptosis was detected by in situ terminal transferase labeling technique; cell migration was detected by cell scratch assay; the expression levels of phosphorylated histone H2A.X (γH2A.X) and radiation-sensitive protein 51 (RAD51) were detected by immunofluorescence.

In OXA group, OXA+si-NC+inh-NC group, OXA+si-PCAT19+inh-NC group, OXA+si-PCAT19+miR-200c-3p group, the cell proliferation rates were (58.83±6.52)%, (59.42±6.86)%, (45.59±6.09)% and (55.71±7.69)%, respectively; the apoptosis rates were (20.06±2.44)%, (20.32±2.66)%, (31.74±4.43)% and (24.60±3.29)%, respectively; the migration rates were (54.50±6.14)%, (56.11±6.72)%, (31.51±4.13)% and (48.59±7.26)%, respectively; the relative fluorescence intensities of γH2A.X were 1.00±0.08, 0.97±0.12, 4.84±0.82 and 2.11±0.41, respectively; the relative fluorescence intensities of RAD51 were 1.00±0.06, 1.08±0.15, 0.22±0.04 and 0.55±0.08, respectively. There were no significant differences between OXA+si-NC+inh-NC group and OXA group (all P>0.05). The above indexes of OXA+si-PCAT19+inh-NC group were compared with those of OXA+si-NC+inh-NC group, the above indexes in OXA+si-PCAT19+miR-200c-3p inh group were compared with those of OXA+si-PCAT19+inh-NC group, the differences were statistically significant (all P<0.05).

Knockdown of LncRNA PCAT19 can affect the proliferation, migration, apoptosis and deoxyribonucleic acid repair of gastric cancer cells by targeting and negatively regulating miR-200c-3p, thereby enhancing the sensitivity of gastric cancer cells to OXA, which may be related to the ATR/CHK1 signaling pathway.

To explore the effects of Wu Wei Han bamboo slips “Yufang” on kidney injury in spontaneously hypertensive rats and its mechanism of action.

To analyze the differential genes between normal kidney tissues and hypertensive kidney tissues in GSE37460, a hypertensive kidney disease dataset in GEO database, and to explore the mechanism of hypertensive kidney injury; Spontaneously hypertensive rats (SHR) were randomly divided into model group (equal volume of distilled water), control group (7.59 mg·kg^-1 valsartan) and experimental-L, -M, -H groups (7.15, 14.29, 28.58 g·kg^-1 “Yufang” granules), with 10 rats in each group; additionally, Wistar-Kyoto (WKY) rats were taken as a normal group (equal volume of distilled water). Six groups were gavaged once a day for 8 consecutive weeks. The levels of urinary microalbumin (mAlb), N-acetyl-β-D-glucosaminidase (NAG) and serum thromboxane (TXB2), 6-keto-prostaglandin F1 α (6-keto PGF1α) were detected by enzyme linked immunosorbent assay. Western blot was used to detect the expression levels of hypoxia inducible factor-1 α (HIF-1α), vascular endothelial growth factor (VEGF) and transmembrane receptor protein 1 (Notch1) in rat kidney.

The data set GSE37460 contained 155 differential genes, 94 of which were up-regulated and 61 were down regulated and pathway enrichment involves pathways such as HIF-1α/VEGF/Notch1. The urinary mAlb levels of normal, model, control and experimental -H groups were (60.83±3.81), (159.60±20.65), (70.45±3.97) and (79.72±9.01) μg·L^-1, respectively; the urinary NAG levels were (34.37±6.92), (91.30±9.05), (44.65±10.09) and (54.79±2.87) ng·L^-1, respectively; the contents of TXB2 in serum were (78.58±3.78), (107.80±5.16), (80.92±4.02) and (85.65±2.17) pg·mL^-1, respectively; the serum 6-keto PGF1α levels were (121.50±3.45), (85.05±2.92), (108.30±2.96), (101.90±3.08) pg·mL^-1, respectively; the relative expression levels of HIF-1 α protein in rat kidney were 0.56±0.03, 1.25±0.02, 0.77±0.01 and 0.83±0.02, respectively; the relative expression levels of VEGF protein were 0.24±0.02, 1.24±0.03, 0.81±0.04 and 0.95±0.02, respectively; the relative expression levels of Notch1 protein were 0.33±0.03, 1.02±0.01, 0.50±0.04 and 0.68±0.01, respectively; there were significant differences in the above indexes between the control and experimental -H groups and the model group (all P<0.05).

The Wuwei Han bamboo slips “Yufang” can improve hypertension-related kidney damage and reduce kidney fibrosis, and its mechanism may be related to the inhibition of the HIF-1α/VEGF/Notch1 signaling pathway.

To observe the clinical efficacy and safety of zoledronic acid concentrate injection combined with alendronate sodium tablets in the treatment of elderly postmenopausal patients with type 2 diabetes mellitus (T2DM) complicated with osteoporosis (OP).

Elderly postmenopausal T2DM patients with OP were divided into control group and treatment group using random number table method. The control group was given oral alendronate sodium tablets, 10 mg per dose, once daily (qd), for a course of 1 year; the treatment group, based on the control group, received additional treatment with zoledronic acid concentrate injection, 5 mg per dose, once a year, via intravenous infusion, for a course of 1 year. The clinical efficacy, pain levels at different time points, bone density before and after treatment, bone metabolism indicators before and after treatment and safety were compared between two groups.

A total of 5 cases were lost during this study, with the final number of patients in the control and treatment groups being 38 cases and 42 cases, respectively. After treatment, the overall effective treatment rates were 84.21% (32 cases/38 cases) for the control group and 97.62% (41 cases /42 cases) for the treatment group, with statistically significant difference (P<0.05). The visual analogue scale (VAS) pain scores for the treatment group after 6 months and 1 year of treatment were (5.62±0.70) and (5.02±0.68) points, respectively, which were significantly lower than the control group’s (6.06±0.75) and (5.65±0.70) points. After 1 year of treatment, the bone density of the lumbar spine L_1-4 were (0.89±0.07) and (0.85±0.08) g·cm^-3 for the treatment and control groups, respectively; the femoral trochanter bone density were (0.78±0.08) and (0.73±0.09) g·cm^-3; the femoral neck bone density was (0.69±0.07) and (0.66±0.06) g·cm^-3; the bone density in the Ward triangle area were (0.79±0.08) and (0.73±0.10) g·cm^-3; the serum levels of type Ⅰ procollagen amino propeptide were (25.60±6.82) and (30.79±6.90) pg·mL^-1; the levels of bone-specific alkaline phosphatase (BALP) were (15.87±4.03) and (17.91±3.71) ng·mL^-1; the levels of Klotho protein were (885.20±32.60) and (810.76±33.15) pg·mL^-1; the levels of 25-hydroxyvitamin D [25-(OH)D] were (35.70±6.72) and (32.29±6.34) ng·mL^-1 for the treatment and control groups, respectively. The above indicators of the treatment group were statistically significantly different from those of the control group (all P<0.05). The main adverse drug reactions in the control group were mainly gastrointestinal discomfort and fatigue, while in the treatment group were mainly fever, muscle and bone pain, gastrointestinal discomfort and fatigue. The overall incidence of adverse drug reactions were 18.42% (7 cases/38 cases) in the control group and 21.43% (9 cases /42 cases) in the treatment group, with no statistically significant difference (P>0.05).

The combined treatment of zoledronic acid concentrate injection and alendronate sodium tablets in elderly postmenopausal T2DM patients with OP is obviously effective, capable of effectively alleviating pain, increasing bone density, raising serum Klotho and 25-(OH)D levels, and reducing BALP levels, with adverse drug reactions being controllable.

To study the in vitro and in vivo pharmacodynamics of dirozalkib.

Prepare dirozalkib solutions with concentrations ranging from 3.81×10^-3 to 1 000.00 nmol·L^-1. The activities of dirozalkib against kinases anaplastic lymphoma kinase (ALK), ALK-L1196M, and ALK-G1202R were evaluated using the Mobility Shift Assay and Radioisotope Filter Binding methods. The inhibitory effect of dirozalkib on cell proliferation was evaluated using the CellTiter-Glo assay in multiple Ba/F3 cell lines transfected with EML4-ALK fusion genes and drug-resistant mutants, at concentrations ranging from 1.53×10^-2 to 1 000.00 nmol·L^-1. Ba/F3-EML4-ALK-L1196M (crizotinib-resistant) cells were subcutaneously inoculated in NOD SCID mice. The tumor-bearing mice were randomly divided into blank group (solvent control), experimental group (50 mg·kg^-1 dirozalkib), control group (50 mg·kg^-1 crizotinib), each group consisted of 9 mice. The mice were gavage once a day, continuous administration over a 14-day period. BALB/c nude mice were used to establish a human lung cancer tumor tissue-derived LU-01-0319R (crizotinib-resistant) patient-derived tumor xenograft (PDX) model. The tumor-bearing mice were randomly divided into blank group (solvent control), experimental group (24 mg·kg^-1 dirozalkib), control group (24 mg·kg^-1 crizotinib), each group consisted of 9 mice. The mice were gavage once a day, continuous administration over a 21-day period. Human lung cancer H228-luc cells were intracranially inoculated in BALB/c nude mice. The tumor-bearing mice were randomly divided into blank group (solvent control), experimental group (100 mg·kg^-1 dirozalkib), control group (100 mg·kg^-1 crizotinib), each group consisted of 9 mice. The mice were gavage once a day, continuous administration over a 14-day period. Assessed the anti-tumor efficacy of dirozalkib.

Dirozalkib significantly inhibited the kinase activities of ALK, ALK-L1196M, and ALK-G1202R [50% inhibiting concentration (IC₅₀) <1.0 nmol·L^-1]. In cells, dirozalkib exhibited significant proliferation inhibitory activity against NCI-H3122 cells harboring EML4-ALK fusion (IC₅₀ = 3.00 nmol·L^-1). Additionally, it demonstrated potent inhibitory activity against multiple cell lines with EML4-ALK fusion and drug-resistant mutants of crizotinib and second-generation ALK inhibitors (IC₅₀: 1.92-62.85 nmol·L^-1). In the crizotinib-resistant Ba/F3-EML4-ALK-L1196M xenograft model, dirozalkib at a dose of 50 mg·kg^-1 had a significant anti-tumor effect, with a relative tumor proliferation rate of 6.14%. In the LU-01-0319R human lung cancer xenograft model (crizotinib-resistant PDX model), the 24 mg·kg^-1 dirozalkib also had a significant tumor inhibitory effect, with a relative tumor proliferation rate of 13.19%. For the H228-luc human lung cancer intracranial inoculation model, dirozalkib at 100 mg·kg^-1 could significantly inhibit tumor growth [BLI value was (569.34±153.65) × 10⁵ photons·s^-1]and could significantly prolong the survival time of the animals.

Dirozalkib effectively inhibits ALK and various resistance mutations associated with first- and second-generation ALK-TKIs, and shows significant antitumor activity in multiple tumor models, including intracranial implantation models.

To investigate the effect of curcumin on lung injury in rats with acute organophosphorus pesticide poisoning (AOPP) through the cytochrome C/apoptotic protease activating factor-1 (CytC/Apaf-1) pathway.

SD rats were divided into control group, model group, inhibitor group, experimental -L and experimental -H groups, with 10 rats in each group. Except for the control group, the rats in the other 4 groups were administrated with 20 mg·kg^-1 oxomethoate to establish the rat model of organophosphorus pesticide poisoning. After the modeling was successful, the rats in the experimental -L and experimental -H groups were given 100 and 200 mg·kg^-1 curcumin by intragastric administration, and the rats in the inhibitor group were given 67.8 mg·kg^-1 YZ-488 intramuscularily, and the model group and control group were given equal volume of normal saline in the same way by intragastric administration and intramuscularily. Five groups of rats were given the drug once a day for 28 days. Mitochondrial membrane potential detection kits were applied to detect mitochondrial membrane potential (MMP). Enzyme-linked immunosorbent assay method was applied to detect levels of serum interleukin-10 (IL-10); apoptosis in lung tissue was detected by TUNEL; Western blot was applied to detect the expression levels of CytC and Apaf-1 proteins in lung tissue.

The MMP of experimental -L and experimental -H groups, control group, model group, and inhibitor group were (0.64±0.05), (0.78±0.09), (0.93±0.06), (0.51±0.04) and (0.76±0.08) RFU·mg^-1, respectively; IL-10 levels were (67.58±6.82), (104.29±11.37), (148.62±13.54), (32.84±3.51) and (98.74±8.76) pg·mL^-1, respectively; the apoptosis rates were (29.37±3.28)%, (16.58±1.87)%, (5.72±0.64)%, (43.68±4.91)% and (17.32±2.14)%, respectively; the relative expression levels of CytC protein were 0.89±0.07, 0.63±0.05, 0.42±0.04, 1.16±0.12 and 0.65±0.06, respectively; the relative expression levels of Apaf-1 protein were 0.73±0.06, 0.48±0.04, 0.32±0.03, 0.97±0.08 and 0.49±0.05, respectively. The above indexes of the model group were statistically significant compared with those in the experimental -L and experimental -H groups, inhibitor group and control group (all P<0.05).

Curcumin may reduce inflammatory response and oxidative stress in rats by inhibiting the CytC/Apaf-1 pathway, alleviate lung tissue and mitochondrial structural damage, and thereby improve lung injury in rats with AOPP.

To explore the effects of niraparib (Nira) on ovarian cancer cell proliferation and migration by inhibiting the wingless MMTV integration site family member (Wnt)/beta-catenin (β-catenin) signaling pathway through the regulation of transcription factor 4 gene (TCF4).

SKOV3 cells were divided into control group (normal culture without any treatment), OE-NC group (10 μmol·L^-1 Nira+ transfection OE-NC treatment) and OE-TCF4 group (10 μmol·L^-1 Nira+ transfection OE-TCF4 treatment), experimental-L, M, H groups (5, 10, 15 μmol·L^-1 Nira treatment). Real-time fluorescence quantitative polymerase chain reaction and Western blotting were used to detect the protein and mRNA expression level of TCF4; cell viability was detected by cell counting kit-8 (CCK-8); and cell invasion ability was detected by Transwell. The expression levels of Wnt/β-catenin pathway-related proteins were detected by immunofluorescence.

The 48 h cell survival rates in control group, experimental-L, -M, -H groups were (98.96±3.13)%, (77.53±7.03)%, (58.31±7.52)% and (35.88±5.97)%, respectively. The relative mRNA expression levels of TCF4 in the control group and the experimental-M group were 1.00±0.16 and 0.45±0.07, respectively; while the relative protein expression levels of TCF4 were 1.00±0.12 and 0.43±0.06, respectively. The number of invasive cells in control group, experimental-M group, OE-NC group and OE-TCF4 group were 115.77±16.57, 60.81±8.80, 66.43±8.98 and 99.25±13.73, respectively; the relative fluorescence intensities of β-catenin were 1.00±0.13, 0.15±0.03, 0.17±0.04 and 0.60±0.11; the relative fluorescence intensities of cancer-Myc were 1.00±0.15, 0.07±0.01, 0.08±0.02 and 0.54±0.09, respectively; the relative fluorescence intensities of matrix metalloproteinase-9 (MMP-9) were 1.00±0.13, 0.06±0.01, 0.07±0.02 and 0.28±0.05, respectively. The control group was compared with experimental-M group, and the OE-TCF4 group was compared with OE-NC group, there were statistically significant differences in the above indexes (all P<0.05).

Nira can inhibit the activity and invasion of ovarian cancer SKOV3 cells, which may be related to the down-regulation of TCF4 to inhibit the activation of Wnt/β-catenin signaling pathway.