OBJECTIVE To evaluate the efficacy and safety of first-line treatments regimens for human epidermal growth factor receptor 2 （HER2）-positive advanced gastric cancer. METHODS Computer searches were conducted on databases such as Web of Science， Embase， CNKI， and VIP in both Chinese and English， and abstracts of papers from the annual meetings of the European Society of Oncology and the American Society of Clinical Oncology were screened. Collected randomized controlled trials （RCTs） on first-line treatment for HER2-positive advanced unresectable or metastatic gastric cancer or gastroesophageal junction adenocarcinoma patients， with a retrieval period from database establishment until April 1， 2025. A network meta-analysis was conducted by two researchers who independently screened literature， extracted data， and evaluated the risk of bias in the study. RESULTS A total of 5 RCTs involving 2 797 patients and encompassing 6 treatment regimens were ultimately included. In the assessment of overall survival， there was a trend towards survival benefit for trastuzumab combined with chemotherapy （Tra_chemo）， pertuzumab combined with trastuzumab and chemotherapy （Per_Tra_chemo）， high-dose trastuzumab combined with chemotherapy （TraHD_chemo）， lapatinib combined with chemotherapy （Lap_chemo）， and pembrolizumab combined with trastuzumab and chemotherapy （Pem_Tra_chemo） compared to chemotherapy alone （chemo）； however， the differences were not statistically significant （P＞0.05）； the top two treatment regimens in terms of the surface under the cumulative ranking curve （SUCRA） were Pem_Tra_chemo （77.8%） and TraHD_chemo （74.2%）. For progression-free survival， there was statistical significance between Per_Tra_chemo and chemo， Pem_Tra_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Per_Tra_chemo （83.0%） and Pem_Tra_chemo （82.8%）. Regarding objective response rate， there was statistical significance between Pem_Tra_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Pem_Tra_chemo（87.4%）and Per_Tra_chemo（72.2%）. In terms of safety， there was statistical significance in the incidence of any level of adverse events between Lap_chemo and chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were chemo（87.1%）and Pem_Tra_chemo（53.8%）. Lap_chemo exhibited a higher incidence of grade ≥3 adverse events compared to chemo， and Per_Tra_chemo showed a higher incidence compared to Tra_chemo （P＜0.05）； the top two treatment regimens in terms of SUCRA were Tra_chemo （79.0%） and chemo （77.6%）. CONCLUSIONS In the first-line treatment of HER2-positive advanced gastric cancer， Pem_Tra_chemo and Per_Tra_chemo regimens have relatively good efficacy， but the safety risks are relatively high， requiring close attention and whole- process management.

The pre-research of medical device standards is of great significance for the enactment and amendment of standards.This study discusses four aspects and explores how to promote more scientific and reasonable pre-research.Based on the pre-research practice of medical device standards project,this study puts forward relevant work ideas and suggestions.

Objective:To explore the association between aldehyde dehydrogenase 2 (ALDH2) gene polymorphisms and abnormal liver function-induced by acetaminophen (APAP) drugs.Methods:An ALDH2 gene knockout mouse model was constructed using CRISPR/Cas9 gene editing technology. The obtained heterozygous mice were mated with opposite sex of heterozygotes. Genomic DNA was extracted from the tail of the offspring mouse. The polymerase chain reaction (PCR) method was used to determine the ALDH2 genotype. APAP was further used to induce acute drug-induced liver injury models in wild-type and ALDH2 knockout mice. Blood and liver tissues of mice were collected for liver function index, HE staining, F4/80 immunohistochemistry, and other detections. The intergroup mean was compared using a one-way ANOVA. The LSD-? t test was used for pairwise comparison. Results:ALDH2 knockout mice were bred successfully. The genotyping of the offspring was segregated into the wild-type (ALDH2 +/+), heterozygous mutant (ALDH2 +/-), and homozygous mutant (ALDH2 -/-), respectively. Biochemical and histological results after APAP modeling showed that the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil) was not significantly increased in the blank control group ( P ?

OBJECTIVE To explore the material basis and mechanism of expectorant and cough relief effects of the fruits of Phellodendron chinense var. glabriusulum Schneid. METHODS The expectorant and cough relief effects of volatile oil and water decoction of the fruits of P. chinense var. glabriusulum Schneid. were studied by ammonia water cough induction and drug expectorant model mice experiments； GC-MS and UPLC-MS technologies were used to identify its volatile oils and non-volatile components of the fruits of P. chinense var. glabriusulum Schneid. The active ingredients， core targets and pathways of expectoration and cough relief were analyzed by network pharmacology. RESULTS The volatile oil （0.8， 0.2 g/kg， calculated by volatile oil） and water decoction （12， 3 g/kg， calculated by crude drug） of the fruits of P. chinense var. glabriusulum Schneid. both had obvious expectorant and cough relief effects， and showed obvious dose-dependent relationship. A total of 38 volatile oil components were identified from the medicinal herbs， and the relative percentage contents of 8 components were greater than 1%， such as α -pinene， myrcene， β -caryophyllene， germanene D， isospathulenol； a total of 69 non-volatile oil components were identified， mainly including phenolic compounds， alkaloids， and flavonoids. The active ingredients screened from the identified components included 13 compounds such as α-pinene， myrcene， chlorogenic acid， luteolin， berberine. There were a total of 55 intersection targets with diseases， and the core targets were tumor necrosis factor （TNF）， epidermal growth factor receptor （EGFR）， vascular endothelial growth factor A （VEGFA）， serine/threonine kinase proteins （AKT1） and Toll-like receptor 4 （TLR4）. The molecular docking results showed that the active ingredients and the core targets had good binding ability. GO functional analysis found that the targets were significantly enriched in biological processes such as the reaction affecting lipopolysaccharides， the positive regulation of peptidyl serine phosphorylation， and the positive regulation of the biosynthesis process of nitric oxide. KEGG pathway enrichment analysis found that the targets were significantly enriched in the signaling pathways such as cancer， non-small cell lung cancer， proteoglycans in cancer. CONCLUSIONS Fruits of P. chinense var. glabriusulum Schneid. have obvious expectorant and cough relief effects， and its material basis may be α-pinene， myrcene， chlorogenic acid， luteolin， berberine， etc.， and mainly act on TNF， EGFR， VEGFA， AKT1， TLR4 and its significantly enriched signaling pathway.

Objective:To carry out the clinical observation and research of OPT intense pulsed light combined parameters in the treatment of lip hairiness.Methods:A total of 94 female patients with lip hairiness who were treated with OPT intense pulsed light depilation were collected, of which 22 were treated with single parameter and 72 were treated with combined parameters, both once a month for 7 months. The treatment effects of the two groups were compared. From October 2013 to October 2019, the patients were collected from the Department of Medical Cosmetology, the Quzhou Affiliated Hospital of Wenzhou Medical University.Results:With the increase of treatment times, the curative effect of patients gradually appeared, and the χ 2 value was 10.87 in the single parameter group and 105.25 in the combined parameter group. The difference was statistically significant ( P<0.05). There was no statistical significance in the single parameter array between the two comparisons of different treatment times; there was statistical significance in the combined parameter group. The χ 2 value of treatment (1 vs. 3) times was 26.05, (1 vs. 7) times was 73.3, (3 vs. 7) times was 23.82 ( P<0.017). There was significant difference in the constituent ratio and total effective rate between the two groups after 3 and 7 times of treatment. The total effective rate of 3 times of treatment was 36.36% in single parameter group and 70.83% in combined parameter group; The total effective rate of 7 times of treatment was 59.09% in the single parameter group and 81.94% in the combined parameter group ( P<0.05). Conclusions:Combined parameters OPT intense pulsed light therapy has better effect on lip hairiness than single parameter, and the treatment is safe and has good clinical application value.

We reviewed the data of an 18-year-old male patient complained of weakness of limbs and hypokalemia for 6 months. CT scan revealed left adrenal adenoma. He was diagnosed as primary aldosteronism(PA). Laboratory tests showed hypokalemia and hyperaldosteronemia. After potassium supplement and blood pressure lowering treatment, laparoscopic resection of the left adrenal adenoma was performed, and severe hyperkalemia occured 2 hours after surgery(maximum serum potassium 7.02 mmol/L). After hyperrisotonic glucose+ insulin(10% glucose 200 ml+ 50% glucose 40 ml+ insulin 8U)+ cation exchange resin(Sodium Polystyrene Sulfonate 20 g) treatment, serum potassium returned to normal range within 12 hours. The plasma aldosterone, blood potassium and blood pressure returned to normal during the 5-month follow-up. According to the experience of this case report, after resection of aldosteronoma, the changes of serum electrolyte should be closely monitored, the occurrence of hyperkalemia should be vigilant.

Objective:To investigate the prognosis of severe hyperbilirubinemia in full-term infants who met the exchange transfusion criteria and were treated by blood exchange transfusion and phototherapy.Methods:A total of 168 full-term infants with severe hyperbilirubinemia who met the criteria for exchange transfusion and were hospitalized in the Neonatology Department of seven tertiary hospitals in Hebei Province from June 2017 to December 2018 were retrospectively included. According to the treatment protocol, they were divided into two groups: exchange transfusion group (38 cases) and phototherapy group (130 cases). Two independent sample t-test and Chi-square test were used to compare the clinical manifestations and follow-up results between the two groups. Multivariate logistic regression was used to analyze the risk factors for poor prognosis. Results:Neonatal severe hyperbilirubinemia in the exchange transfusion and phototherapy group were both mainly caused by hemolytic disease [42.1%(16/38) and 29.2%(38/130)], sepsis [28.9%(11/38) and 11.5%(15/130)] and early-onset breastfeeding jaundice [15.8%(6/38) and 11.5%(15/130)]. Total serum bilirubin level on admission in the exchange transfusion group was significantly higher than that in the phototherapy group [(531.7±141.3) vs (440.0±67.4) μmol/L, t=3.870, P<0.001]. Moreover, the percentage of patients with mild, moderate and severe acute bilirubin encephalopathy in the exchange transfusion group were higher than those in the phototherapy group [15.8%(6/38) vs 3.8%(5/130), 7.9%(3/38) vs 0.8%(1/130), 13.2%(5/38) vs 0.0%(0/130); χ2=29.119, P<0.001]. Among the 168 patients, 135 were followed up to 18-36 months of age and 12 showed poor prognosis (developmental retardation or hearing impairment) with four in the exchange transfusion group (12.9%, 4/31) and eight in the phototherapy group (7.7%, 8/104). Multivariate logistic regression analysis showed that for full-term infants with severe hyperbilirubinemia who met the exchange transfusion criteria, phototherapy alone without blood exchange transfusion as well as severe ABE were risk factors for poor prognosis ( OR=14.407, 95% CI: 1.101-88.528, P=0.042; OR=16.561, 95% CI: 4.042-67.850, P<0.001). Conclusions:Full-term infants who have severe hyperbilirubinemia and meet the exchange transfusion criteria should be actively treated with blood exchange transfusion, especially for those with severe ABE, so as to improve the prognosis.

Objective To investigate the roles of long noncoding RNA-myocardial infarction-associated transcript (MIAT) on lens epithelial cells (LECs) fibrosis induced by transforming growth factor-β2(TGF-β2).Methods LECs line (SRA01/04) was cultured in conventional DMEM (normal control group) and DMEM containing 10 ng/ml TGF-β2(TGF-β2 induced group) for 48 hours.The morphology of the cells was observed under the optical microscope,and the relative expression levels of M IAT,E-cadherin (E-cad),α-smooth muscle action (α-SMA),collagen Ⅰ (Coll Ⅰ) in protein level and mRNA level were detected by real-time fluorescence quantitative PCR and Western blot,respectively.The cells cultured in DMEM or DMEM containing 10 ng/ml TGF-β2 were transfected by siNRA empty carrier (siNRA group,siNRA+TGF-β2 group) and siRNA-MIAT (siRNA-MIAT group,siNRA-MIAT+ TGF-β2 group) for 48 hours,and the morphology of the cells was observed under the optical microscope,and the relative expression levels of MIAT,E-cadherin (E-cad),α-smooth muscle action (α-SMA),collagen Ⅰ (Coll Ⅰ) in protein level and mRNA level were detected by real-time fluorescence quantitative PCR and Western blot.Results The cells in the normal control group showed the round and polygon in shape,and those in the TGF-β2 induced group showed the spindle-like.Compared with the normal control group,the relative expression levels of MIAT mRNA,α-SMA mRNA and Coll Ⅰ mRNA were significantly elevated (2.497 ± 0.644 vs.0.827 ± 0.062;2.951 ±0.146 vs.1.085±0.517;2.115 ±0.090 vs.1.002 ± 0.088),and the expression of E-Cad mRNA was significantly reduced (0.102±0.027 vs.1.020±0.262) in the TGF-β2 induced group (P =0.045,0.004,0.000,0.025).The expressions of MIAT,α-SMA,Coll Ⅰ and E-Cad showed a similar trend between two groups.The relative expressions of MIAT protein and mRNA were evidently reduced in the SiRNA-MIAT group compared with the siRNA empty vector group (all at P＜0.05).Compared with the siRNA+TGF-β2 group,the relative expressions of α-SMA and Coll Ⅰ in protein and mRNA levels were significantly reduced,and the expressions of E-cad protwin and mRNA were elevated in the siRNA-MIAT+TGF-β2 group (all at P＜0.01).Conclusions MIAT might participate in TGF-β2-induced LECs-EMT.The down-regulation of MIAT in the LECs inhibits the fibrosis of LECs.

Objective To investigate the expression of serum 25(OH)D,vitamin D receptor (VDR)and vitamin D1-α hydroxylase (CYP27B1) in intestinal mucosa tissues of patients with inflammatory bowel disease (IBD).Methods From January 1st to December 31st in 2014,105 patients with IBD were enrolled,among them there were 49 cases of ulcerative colitis (UC) and 56 cases of Crohn's disease (CD);there were 20 cases in remission,26 cases in mild active phase,37 cases in moderate active phase and 22 cases in severe active phase;and 50 cases with lesions located in the left colon and 55 cases with lesions located in the right colon.At the same period,45 healthy individuals were also recruited as controls,whom were suspected as IBD but at last proved healthy.The lactulose and mannitol absorption ratio (LMR),serum endotoxin,tumor necrosis factor-α (TNF-α) and 25(OH)D levels,and the expressions of VDR and CYP27B1 in the intestinal mucosa tissues were detected in all the subjects.T test,one-way analysis of variance and chi square test were used for statistical analysis.Results The LMR,endotoxin and TNF-α levels of UC group were (63.2 ± 13.9)％,(118.9 ± 19.7) EU/mL,and (109.6 ± 18.4) ng/L,respectively,which were higher than those of the healthy control group ((3.3 ± 1.2)％,(34.2 ±5.6) EU/mL,and (0.6±0.3) ng/L);the level of 25 (OH)D was (36.6± 9.7) nmol/L,which was lower than that of healthy control group ((49.6± 10.9) nmol/L),and all the differences were statistically significant (t =28.796,29.284,27.817 and 6.118,all P＜0.05).LMR,endotoxin and TNF-α levels of CD group were (52.9±11.3)％,(96.4±10.6) EU/mL and (83.0±16.1) ng/L,respectively,which were higher than those of the healthy control group,25(OH)D level was (44.4±9.4) nmol/L,which was lower than that of healthy control group,and all the differences were statistically significant (t=34.555,39.716,34.293 and 0.012,all P＜0.05).The differences in LMR,endotoxin,TNF-α and 25 (OH)D levels among healthy control group,remission group,mild active group,moderate active group and severe active group were statistically significant (F=286.731,385.690,657.830 and 18.932,all P＜0.01) which was dependent on the disease activity.Compared with those of the healthy controls,the levels of LMR,endotoxin and TNF-α of the left colon group and the right colon group increased,and 25(OH)D levels decreased.The high expression rates of VDR in UC group and CD group were 36.7％ (18/49) and 55.4％ (31/ 56),respectively,which were both lower than that of healthy control group (80.0％ (36/45)),and the differences were statistically significant (x2 =38.574 and 13.837,both P＜0.05).The high expression rates of CYP27B1 of UC group and CD group were 26.5％ (13/49) and 35.7％ (20/56),respectively,which were both higher than that of healthy control group (22.2％ (10/45)),and the differences were statistically significant (x2=6.499 and 4.430,both P＜0.05).The differences in the high expression rates of VDR and CYP27B1 among healthy control group,remission group,mild active group,moderate active group and severe active group were statistically significant (F=33.470 and 27.142,both P＜0.01),which was dependent on the disease activity.Compared with that of the healthy control group,the high expression rates of VDR of the left colon group and the right colon group decreased,and the high expression rates of CYP27B1 increased.Conclusion There is vitamin D metabolic imbalance in IBD patients,as well as low serum 25(OH)D level,low rate of high VDR expression in colonic mucosa tissues and high rate of high CYP27B1.

Objective To explore the role and mechanism of protein disulfide isomerase A3 (PDIA3) in abnormal colonic mucosa immune response of irritable bowel syndrome (IBS) rats with visceral hypersensitivity.Methods A total of 48 SD rats were divided into blank control group (n=12),empty virus group (IBS-1) (n=12),PDIA3 silencing group (IBS-2) (n=12) and model control group(IBS-3) (n=12).The expression of CD103 in ileocecus colonic tissues was detected by immunohistochemistry.Dendritic cells (D C) of mesenteric lymph node were isolated by flow cytometry.CD4+/CD8+ T cells of spleen were separated by immune-magnetic beads sorting technique.DC and CD4+/CD8+ T cells were co-cultured.The proliferation ability of lymphocytes promoted by DC was measured by methyl thiazolyl tetrazolium (MTT).The secretion levels of interlcukin (IL) 4 and IL-9 of CD4+/CD8+ T cells stimulated by DC were determined by enzyme linked immunosorbent assay (ELISA) method.Independent sample t-test was performed for statistical analysis.Results The cell number of CD103 positive DC of rats colon of blank control group,IBS-3 group was 6.25±1.14 and 10.83± 1.03(t=10.07,P＜0.05);that of IBS-2 group was 7.42 ± 0.90,and compared with that of IBS-3 group,the difference was statistically significant (t=-9.25,P ＜ 0.05).The MTT value of CD4+ T cells proliferation stimulated by DC of blank control group and IBm3 group was 0.54±0.01 and 0.60±0.01 (t=3.373,P＜0.05);that of IBS-2 group was 0.53±0.01,and compared with that of IBS-3 group,the difference was statistically significant (t =-3.139,P ＜ 0.05).The MTT value of CD8+ T cells proliferation stimulated by DC was 0.52±0.01 and 0.59±0.00(t=3.539,P＜0.01);that of IBS-2 group was 0.54±0.01,and compared with that of IBS-3 group,the difference was statistically significant (t=-3.183,P＜0.05).The level of IL-4 secreted by CD4+T cells promoted by DC of blank control group and IBS-3 group was 10.24±0.09 and 16.61±1.00 (t=3.222,P＜0.05);that of IBS-2 group was 11.75±0.54,and compared with that of IBS-3 group,the difference was statistically significant (t=-3.539,P＜0.01).The level of IL-9 secreted by CD4+T cells stimulated by DC of blank control group and IBS-3 group was 15.86±10.19 and 43.51±11.32 (t=4.529,P＜0.05);that of IBS-2 group was 29.05±2.09,and compared with that of IBS-3 group,the difference was statistically significant (t=-6.841,P＜0.01).The level of IL-4 secreted by CD8+T cells promoted by DC of blank control group and IBS-3 group was 7.35±0.12 and 13.91±0.57 (t=19.557,P＜0.01);that of IBS-2 group was 8.63± 0.24,and compared with that of IBS-3 group,the difference was statistically significant (t =-14.782,P＜0.01).The level of IL-9 secreted by CD8+T cells stimulated by DC of blank control group and IBS-3 group was 29.12±5.14 and 60.70±11.02 (t=4.122,P＜0.05);that of IBS-2 group was 37.17±2.65,and compared with that of IBS-3 group,the difference was statistically significant (t=-3.255,P＜ 0.05).Conclusions Protein disulfide isomerase A3 may mediate the process of DC activating T lymphocyte levels of related cytokines,cause abnormal immune response of colonic mucosa and promote the genesis of IBS visceral hypersensitivity.