OBJECTIVE To evaluate the efficacy and safety of amoxicillin combined with proton pump inhibitor （PPI） or potassium-competitive acid blocker （P-CAB） for Helicobacter pylori （Hp） eradication. METHODS Randomized controlled trial （RCTs） on amoxicillin combined with PPI or P-CAB for Hp eradication were retrieved from PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang， and VIP data. The search time frame was from database inception to September 5， 2025. After literature screening， data extraction， and quality assessment， a network meta-analysis was performed using Stata 17.0 software. RESULTS A total of 12 RCTs involving 5 515 patients were included， encompassing 8 therapeutic regimens： PPI combined with high-dose amoxicillin for 14 days （TR1）， PPI combined with low-dose amoxicillin for 14 days （TR2）， P-CAB combined with high-dose amoxicillin for 7 days （TR3）， P-CAB combined with high-dose amoxicillin for 14 days （TR4）， P-CAB combined with high-dose amoxicillin for 10 days （TR5）， P-CAB combined with low-dose amoxicillin for 7 days （TR6）， P-CAB combined with low-dose amoxicillin for 14 days （TR7）， and P-CAB combined with low-dose amoxicillin for 10 days （TR8）. The network meta-analysis results showed that， in terms of intention-to-treat Hp eradication rates， the eradication rates of TR5 and TR4 were significantly higher than those of TR3， TR8， TR6 and TR1 （ P ＜0.05）. The surface under the cumulative ranking curve （SUCRA） values from highest to lowest were： TR4 （89.7%）＞TR5 （82.3%）＞TR7 （71.5%）＞ TR2 （48.6%）＞TR1 （43.9%）＞TR8 （28.7%）＞TR3 （22.7%）＞TR6 （12.6%）. Regarding safety， the incidence of adverse reactions in TR3 and TR5 was significantly lower than that in TR1 （ P ＜0.05）. The SUCRA values from highest to lowest were： TR1 （91.3%）＞TR4 （79.8%）＞TR5 （55.0%）＞TR7 （50.9%）＞TR8 （41.3%）＞TR2 （36.4%）＞TR3 （27.6%） ＞TR6 （17.7%）. CONCLUSIONS Although the regimen of P-CAB combined with high-dose amoxicillin for 14 days demonstrates the best efficacy， the combination of P-CAB with high-dose amoxicillin for 10 days exhibits a better balanced profile in terms of both efficacy and safety.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

ObjectiveTo investigate the current status of HIV-related health service uptake among cross-border couples (Chinese husbands and Myanmar wives) in Dehong Dai and Jingpo Autonomous Prefecture (hereinafter referred to as Dehong Prefecture), and to provide evidence for optimizing HIV prevention and control strategies in border areas. MethodsA cross-sectional survey was conducted from September 2022 to September 2023 among 14 662 cross-border couples (Chinese husbands and Myanmar wives) in Dehong Prefecture. Data on sociodemographic characteristics, HIV/AIDS knowledge awareness, and utilization of HIV-related health services within the past year were collected. Multivariable logistic regression was used to analyze factors associated with HIV testing uptake among husbands and wives. ResultsA total of 29 324 individuals (14 662 couples) were included. The overall awareness rate of HIV/AIDS was 82.09%, with the rate among husbands significantly higher than that among wives (85.17% vs. 79.01%, P<0.001). Overall, 94.98% of participants had received at least one HIV-related health service, and the HIV testing rate in the past year was 65.52%. Multivariable logistic regression analysis showed that, compared with participants married for 0‒3 years, those married for 4‒10 years and ≥11 years were more likely to have received HIV testing. The corresponding ORs were 1.344 (95%CI: 1.187‒1.521) and 1.381 (95%CI: 1.211‒1.574) among husbands, and 1.308 (95%CI: 1.155‒1.481) and 1.344 (95%CI: 1.178‒1.533) among wives, respectively. Compared with those holding a marriage certificate, those possessing a border marriage registration certificate were positively associated with HIV testing uptake, with ORs of 1.710 (95%CI: 1.575‒1.857) among husbands and 1.700 (95%CI: 1.565‒1.847) among wives. Compared with illiterate participants, those with primary school education showed lower testing rates, with ORs of 0.738 (95%CI: 0.650‒0.837) among husbands and 0.827 (95%CI: 0.766‒0.891) among wives. Additionally, a history of sexually transmitted diseases (OR=3.656, 95%CI: 1.243‒15.589) and participation in the New Rural Cooperative Medical Scheme (OR=1.51, 95%CI: 1.179‒1.935) were independently associated with higher testing rates among husbands. ConclusionThe overall utilization of HIV-related health services among cross-border couples in Dehong Prefecture is satisfactory, but significant gender disparities exist, with foreign wives showing lower rates of knowledge awareness and lower proportions obtaining such knowledge through certain channels compared with their Chinese husbands. Couples with shorter marriage duration, those with primary school education, and those not included in the border marriage registration system are vulnerable groups with lower HIV testing uptake. Future interventions should prioritize cross-border marriage families at the early stage of entry and in the newly married period. Based on the border marriage registration management system and primary healthcare networks, health education and HIV testing services targeting foreign spouses should be strengthened to improve service accessibility and equity.

ObjectiveTo screen and evaluate the antidepressant compounds of Curcumae Rhizoma， and explore its mechanism of regulating the nuclear factor erythroid 2-related factor 2（Nrf2）/glutathione（GSH） peroxidase 4（GPX4）/GSH pathway from an antioxidant perspective. MethodsThe antioxidant activities in vitro of 11 characteristic components from Curcumae Rhizoma， including curcumol， curgerenone， curdione， curzerene， curcumenol， curcumenone， dehydrocurdione， isocurcumenol， furanodienone， furanodiene and zederone， were detected using 1，1-diphenyl-2-picrylhydrazyl（DPPH） and 2，2'-azinobis-（3-ethylbenzothiazoline-6-sulphonic acid） diammonium salt（ABTS） radical scavenging assays. The depression in Drosophila melanogaster was induced by chronic unpredictable mild stress（CUMS）， and W1118 wild-type male D. melanogaster were randomly divided into blank group， model group， curcumol group， curgerenone group， curdione group， curzerene group， curcumenol group，curcumenone group， dehydrocurdione group， isocurcumenol group， furanodienone group， furanodiene group， zederone group and fluoxetine group（10 μmol·L^-1）. The treatment groups received a dose of 0.1 g·L^-1 of 11 characteristic components from Curcumae Rhizoma， while the blank and model groups were administered equivalent volumes of solvent. The sucrose preference test， climbing test and forced swimming test were used to evaluate the behavioral indicators of depression in D. melanogaster. Liquid chromatography-mass spectrometry（LC-MS） was used to detect the levels of 5-hydroxytryptamine（5-HT） and dopamine（DA） in the brain of D. melanogaster， and the entropy weight method was used to comprehensively evaluate neurobehavioral and neurotransmitter indicators， resulting in the identification of the antidepressant active components of Curcumae Rhizoma. In addition， a mouse depression model was established by CUMS， and C57BL/6J mice were randomly divided into blank group， model group， low and high dose groups of curzerene（0.5， 1 mg·kg^-1）， and fluoxetine group（10 mg·kg^-1） to confirm the antidepressant effect of the optimal active ingredient by behavioral analysis. Flow cytometry was used to detect the content of reactive oxygen species（ROS） in the hippocampus of mice from each group. Enzyme-linked immunosorbent assay was used to detect the contents of adenosine triphosphate（ATP）， superoxide dismutase（SOD）， catalase（CAT） and GSH. Transmission electron microscope（TEM） was used to observe the effect of curzerene on the ultrastructure of mitochondria in hippocampal tissue. Western blot was performed to determine the level of Nrf2 protein， and Nrf2 inhibitor（ML385） was used to verify the relationship between the antidepressant effect of curzerene and regulation of Nrf2. Real time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect the effect of curzerene on the mRNA expression level of GPX. ResultsIn vitro antioxidant experiments showed that curzerene and curgerenone exhibited the most significant ability to scavenge free radicals， and comprehensive evaluation results of entropy weight method indicated that curzerene stood out as the most promising active component. Compared with the blank group， the model group exhibited a significant decrease in sucrose preference coefficient and the number of times entering the open field center（P<0.01）， as well as a significant increase in immobility time in the forced swimming and tail suspension tests（P<0.01）， and the ROS content in hippocampus significantly elevated（P<0.01）， while the ATP content significantly reduced（P<0.01）. In the hippocampal neurons of the model group， mitochondrial cristae were disordered， with vacuolation of the inner membrane and severe damage. Nrf2 protein expression level in the model group was significantly decreased（P<0.05）， and the antioxidant enzymes SOD， CAT and GSH contents were also significantly reduced（P<0.05， P<0.01）， and the gene expression levels of GPX1， GPX4 and GPX7 were significantly decreased（P<0.01）. Compared with the model group， the high-dose group of curzerene showed a significant increase in the sucrose preference coefficient and the number of times entering the open field center（P<0.05）， as well as a significant decrease in immobility time in the forced swimming and tail suspension tests（P<0.05， P<0.01）. The ROS content in the hippocampus of the high-dose group of curzerene was significantly reduced（P<0.01）， while the ATP content was significantly increased（P<0.05）. The neuronal mitochondrial damage in the hippocampus of the high-dose group of curzerene was alleviated， and the expression level of Nrf2 protein was significantly increased（P<0.05）. The Nrf2 inhibitor ML385 reversed the improvement of curzerene on depressive behaviors in CUMS mice. The GSH content in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.01）， while there were no significant differences in SOD and CAT contents. The expression level of GPX4 gene in the hippocampal neurons of the high-dose group of curzerene was significantly increased（P<0.05）， while there were no significant differences in other GPX genes. ConclusionCurzerene is the best component with antidepressant activity in Curcumae Rhizoma. It may improve mitochondrial dysfunction to exert its antidepressant effect by regulating Nrf2 and its downstream GPX4/GSH pathway rather than CAT or SOD pathways.

AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Chronic thromboembolic pulmonary hypertension(CTEPH)is a form of pulmonary hypertension caused by unresolved thrombi and chronic embolization in the pulmonary arteries.In recent years,multi-omics technologies have provided multidimensional insights into CTEPH.Single-cell transcriptomics has identified key pathogenic cell subsets and related mechanisms;Genomics has revealed susceptibility genes associated with coagulation;Proteomics has uncovered differentially expressed proteins closely linked to vascular remodeling;And metabolomics has characterized metabolic reprogramming features and potential sub-typing biomarkers.This review summarizes re-cent advances in these omics fields and discusses their value and prospects in mechanistic exploration,biomarker discovery,and personalized therapeutic strategies.

Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

The refinement of nasal tip rotation and projection is a critical step in tip sculpting in augmentation rhinoplasty. Autologous cartilage material is widely used in rhinoplasty due to its good histocompatibility and support. However, in clinical work, the profile of the nasal tip after autologous cartilage rhinoplasty often changes over time, with the phenomenon of downward rotation of the nasal tip and reduced tip projection. Thus, how to construct a stable nasal tip cartilage framework is a common problem for clinicians. This review encompasses the relevant content of nasal tip dynamics and measurement, the recent approaches to constructing the nasal tip cartilage framework, the factors influencing tip rotation and projection after rhinoplasty, the dynamic changes in nasal tip morphology after surgery, and summarizes the method to mitigate the downward rotation of the nasal tip and variations in nasal tip projection, with the aim to guide intraoperative adjustment of nasal tip morphology.