OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） as first-line therapy for advanced gastric cancer. METHODS PubMed， Web of Science， Embase， The Cochrane Library， Wanfang Data， CNKI， and VIP databases were searched to collect phase Ⅲ clinical randomized controlled trials （RCTs） on ICIs as first-line therapy for advanced gastric cancer， as well as abstracts from relevant oncology academic conferences. The search period spanned from database inception to June 1， 2025. After screening literature， extracting data， and assessing quality， a network meta-analysis was performed using R software version 4.3.2. RESULTS A total of 8 studies involving 7 801 patients were included. Network meta-analysis results showed that， in terms of efficacy， compared with chemotherapy （Chemo）， SHR-1701_Chemo， Cadonilimab_Chemo， Sintilimab_Chemo， Pembrolizumab_Chemo， and Tislelizumab_Chemo significantly prolonged median overall survival （OS） and median progression free survival （PFS） in patients （P＜0.05）； whereas Nivolumab_Chemo only significantly improved median PFS （P＜0.05）. Surface under the cumulative ranking curve （SUCRA） results indicated that the top 2 interventions for median OS were SHR-1701_Chemo and Cadonilimab_Chemo； for PFS， the top 2 were Cadonilimab_Chemo and SHR-1701_Chemo. For patients with combined positive score （CPS） ≥5 points for programmed death-ligand 1 （PD-L1）， Cadonilimab_Chemo and SHR- 1701_Chemo also demonstrated the optimal OS and PFS benefits （P＜0.05）. Regarding safety， there were no statistically significant differences among the interventions in the incidence of any adverse events （AEs） or grade ≥3 AEs （P＞0.05）. The SUCRA ranking for the incidence of any AEs showed the top 2 were SHR-1701_Chemo and Chemo； for grade ≥3 AEs， the top 2 were Chemo and Sugemalimab_Chemo. CONCLUSIONS For patients with advanced gastric cancer， Cadonilimab_Chemo and SHR-1701_Chemo demonstrate the best benefits in terms of OS and PFS， with their advantages remaining clear in patients with PD-L1 CPS≥5 points. In terms of safety， the risk of developing any AEs and grade ≥3 AEs is relatively lowest with Chemo.

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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.

Objective To investigate the hemodynamic effects of enhanced external counterpulsation(EECP)on cerebral arteries with different stenoses.Methods Zero-dimensional/three-dimensional multiscale hemodynamic models of cerebral arteries with different stenoses were constructed.Numerical simulations of the EECP hemodynamics were performed under different counterpulsation modes to quantify several hemodynamic indicators of the cerebral arteries.Among them,the mean time-averaged wall shear stress(TAWSS)downstream of the stenosis was in the range of 4-7 Pa,a low percentage of TAWSS risk area,and high narrow branch flow were considered to inhibit the development of atherosclerosis and create a good hemodynamic environment.Results For cerebral arteries with 50%,60%,70%,and 80%stenosis,the hemodynamic environment was optimal in counterpulsation mode when the moment of cuff deflation was 0.5,0.6,0.7,and 0.7 s within the cardiac cycle.Conclusions For 50%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.5 s should be selected.For 60%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.6 s should be selected.For 70%or 80%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.7 s should be selected.As stenosis of the cerebral arteries increases,the pressure duration should be prolonged.This study provides a theoretical reference for the EECP treatment strategy for patients with ischemic stroke with different stenoses.

Previous studies have revealed that patients with hypertrophic cardiomyopathy (HCM) exhibit differences in symptom severity and prognosis, indicating potential HCM subtypes among these patients. Here, 793 patients with HCM were recruited at an average follow-up of 32.78 ± 27.58 months to identify potential HCM subtypes by performing consensus clustering on the basis of their echocardiography features. Furthermore, we proposed a systematic method for illustrating the relationship between the phenotype and genotype of each HCM subtype by using machine learning modeling and interactome network detection techniques based on whole-exome sequencing data. Another independent cohort that consisted of 414 patients with HCM was recruited to replicate the findings. Consequently, two subtypes characterized by different clinical outcomes were identified in HCM. Patients with subtype 2 presented asymmetric septal hypertrophy associated with a stable course, while those with subtype 1 displayed left ventricular systolic dysfunction and aggressive progression. Machine learning modeling based on personal whole-exome data identified 46 genes with mutation burden that could accurately predict subtype propensities. Furthermore, the patients in another cohort predicted as subtype 1 by the 46-gene model presented increased left ventricular end-diastolic diameter and reduced left ventricular ejection fraction. By employing echocardiography and genetic screening for the 46 genes, HCM can be classified into two subtypes with distinct clinical outcomes.

Objective To investigate the effects of different immunosuppressive agents on mesangial cell proliferation through a mesangial cell injury model in vitro. Methods Mesangial cell line (HBZY-1) in period of proliferation was cultured in vitro with cytochalasin B for 2 h, then HBZY-1 cells were divided into 5 groups: blank (control) group, cyclosporine A (CsA) group, Tacrolimus (Tac) group, mycophelonate mofetil (MMF) group and rapamycin (RAPA) group. Subsequently,the number of HBZY-1 cells at different time points was measured by using the professional image analysis software after treatment for 6, 12 and 24 h, respectively. Results Damaged HBZY-1 cells recovered in all groups. At 6 h, the number of HBZY-1 cells in Tac group was significantly more than that in control group (P＜0.05), but the difference had no significance between the other treatment groups and control group (P＞0. 05). At 12 h, there was no significant difference in of the number of HBZY-1 cells among the all groups (P＞0. 05). At 24 h, there was no significant difference in the cell number between MMF and control groups (P＞0. 05). CsA, Tac and RAPA resulted in HBZY-1 cell proliferation, and the cell number in CsA and Tac groups was significantly more than that in the other groups (P＜0. 05). As compared with the control group, the cell number in RAPA group was significantly increased (P＜0. 05). Conclusion CsA, Tac, MMF and RAPA contribute to recovery of damaged HBZY-1 cells, but CsA and Tac result in over-proliferation of HBZY-1 cells. RAPA and MMF can prevent HBZY-1 cells against over-proliferation, and MMF scarcely results in HBZY-1 cell proliferation.

Objective To construct a new recombinant immunotoxin expression vector by using human VEGF165 and a truncated pseudomonas exotoxin A ramification (PE38) gene, and explore the expression of the VEGF165-PE38 fusion protein in HEK293 cells. Methods VEGF165 was cloned by polymerase chain reaction (PCR). PE38 gene was gained from an vector plasmid pRB391 by restriction endonuclease digestion, and then inserted to the eukaryotic expression vector pIRES2-EGFP. After the eukaryotic recombinant vector pIRES2-VEGF165-PE38-EGFP was identified by restriction endonuclease digestion and sequence analysis, the vector was transfected into HEK293 cells by liposome protocol. RT-PCR and ELISA method was used to confirm the expression of the fusion gene in the HEK293 cells. Results Restriction endonuclease digestion and sequence analysis revealed the VEGF165-PE38 fusion gene was cloned into the eukaryotic expression plasmid vector pIRES2-EGFP successfully. The pIRES2-VEGF165-PE38-EGFP fusion gene could express in the HEK293 cells. Conclusion The result provide the basis for search of the targeted cytotoxic activity to tumor vascular endothelial cells and may have some potential value in clinical application.

This study was aimed to investigate the anti-proliferation effect of interferon-alpha (IFN-alpha) on leukemic U937 cells and its mechanism. The U937 cells were given with various concentrations of IFN-alpha (500, 1 000, 2,000, 3,000 and 4,000 U/L) and at different time (0, 12, 24, 36, 48 hours), the inhibitory ratio was measured by MTT assay, apoptosis rate was detected by flow cytometry (FCM), the expression of cell cycle-associated cyclin E mRNA was measured by RT-PCR. The results showed that IFN-alpha (2,000 U/L) could cause apoptosis, after being treated by various concentrations of IFN-alpha, the growth of U937 cells was inhibited significantly, the apoptosis rate was 25.82% - 70.54% (P < 0.01), the cycle-associated cyclin E mRNA expression decreased, the growth of U937 cells was significantly inhibited, the suppression of U937 by IFN-alpha was both in time-and dose-dependent manner. It is concluded that IFN-alpha has apparent anti-proliferation and apoptosis-inducing effects on U937 cells. These results will provide strong laboratory evidence for IFN-alpha clinical application in leukemia therapy.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Cyclin E ; biosynthesis ; genetics ; Humans ; Interferon-alpha ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; U937 Cells

OBJECTIVE:To investigate mycoplasma infection and drug susceptibility in patients with non-gonococcus urethritis (NGU),and to provide reference for rational use of antibotics in patients with mycoplasma infection.METHODS:Mycoplasma diagnosis reagent box was used to culture and identify mycoplasma from suspected patients with NGU,and to conduct drug sensitivity test.RESULTS:360 cases of positive mycoplasma among 711 suspected NGU patients (positive rate was 50.66%),Uu positive were 235 cases (positive rate 33.05%);Mh positive were 30 cases (positive rate 4.22%);Uu+Mh positive were 95 cases (positive rate 13.36%).Results of drug sensitivity test showed josamycin,doxycycline,minocycline,clarithromycin and tetracycline were best choice for Uu single infection,and josamycin,doxycycline,minocycline for Uu+Mh infection.CONCLUSION:Uregenital tract infections are mainly caused by Uu.Clinical medication for mycoplasma infection should be in accordance with the type of mycoplasma and results of drug sensitivity test.

BACKGROUND: The environmental change of regeneration of peripheral nerve fiber can accelerate the regeneration of nerve fiber and the recovery of nerve function. Physiotherapy can improve the local microcirculation of the injured area, and promote and stimulate the recovery course of trauma. Therefore, whether choosing different physiotherapies and controlling irradiation dose can speed up the regeneration of nerve fiber?OBJECTIVE: To observe the effects of different physiotherapies in promoting the regeneration of injured nerve fiber.DESIGN:Randomized grouping and controlled animal experiment.SETTING: Laboratory of Anthropotomy and Histo-Embryology Department,Peking University Health Science Center.MATERIALS: The experiment was conducted in the Laboratory of Anthropotomy and Histo-Embryology Department, Peking University Health Science Center, from September 2001 to September 2002. Fifteen adult male SD rats, weighting 185-220 g, were selected.INTERVENTIONS: The model of sciatic nerve injury was established and randomly assigned to 3 groups. Bio-spectrum group and infrared group with 5rats in each received the corresponding physical irradiation. Injury control group was given no irradiation. The slices of sciatic nerve at the operation side of the animals in the three groups were collected on day 14 after operation. The degeneration rate of the injured nerve fiber was observed under the optical microscope to make indirect assessment of the protective effect of physiotherapy after the nerve was injured.MAIN OUTCOME MEASURES: The degeneration rate of nerve fibers at the breakpoint and at 4 points near the spinal cord ( 1,2,3,4 mm) and away from the spinal cord( 1,2,3,4 mm).difference in the degeneration rate of nerve fibers at the breakpoint away from the spinal cord in bio-spectrum group and infrared group as compared with the degeneration rate of nerve fibers in bio-spectrum group(68% ) and infrared group(89% ) was obviously reduced and that in control group was the the spinal cord in the 3 groups showed decreasing trend: the closer to the spinal cord, the fewer the degenerative nerve fibers. The number of degenerative nerve fibers was the smallest in bio-spectrum group, second smallest in infrared group, and the largest in control group.CONCLUSION: The assisting physiotherapy can decrease the number of regenerative nerve fibers, thus promoting and accelerating their recovery. Irradiation with bio-spectrum equipment is more effective.