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 explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Objective To analyze the global literature related to functional cure of hepatitis B from 2019 to 2023 by using bibliometric analysis methods,so as to help researchers understand the research hotspots and trends in this field.Methods The literature related to the topic of functional cure of hepatitis B included in the Science Citation Index Expanded(SCI-Expanded)of the Web of Science Core Collection from 2019 to 2023 was searched.By using VOSviewer and CiteSpace visual analysis tools,analyses were conducted from the perspectives of publication trends,international research cooperation networks,and keyword emergence,and were elaborated with the specific contents of the related literature to elucidate research hotspots and trends.Results A total of 600 eligible papers in this field were included.Keyword co-occurrence and thematic clustering suggested that the main research directions of functional cure were:serum biomarkers for prediction and monitoring of functional cure,functional cure and immunity,nucleoside analog discontinuation,interferon therapy,and long-term prognosis of functional cure.The research contents of the ESI highly cited original research papers were similar to the clustering of the above,but showed more attention on the novel agents for functional cure.The content of the keyword emergence map showed that hotspots of interest changed from virologic mechanisms and serum markers,to nucleoside analog discontinuation and interferon therapy,and finally to immunologic mechanisms and new drug.Conclusion The research hotspots and trends of functional cure of hepatitis B were focused on virological mechanism,serum markers,immunological mechanism,nucleoside analog discontinuation,interferon therapy,and long-term prognosis after cure.

Objective To conduct a bibliometric analysis of relevant literature on liver failure caused by viral hepatitis from the past five years,and to help researchers understand the current status and hotspots in this field,and to provide insights into future research trends.Methods Based on the Science Citation Index Expanded(SCI-Expanded)data from Web of Science Core Collection,visualization analysis and mapping were conducted through VOSviewer and CiteSpace software to generate visual representations of international research collaboration networks,keyword co-occurrence clustering,and keyword bursts.Results From 2019 to 2023,a total of 873 relevant literature were included,with a total citation frequency of 7 364 and an average citation frequency of 8.44.Among them,China had the highest number of publications(458 articles,52.46%)and had the most cooperation with the United States.The research hotspots of viral hepatitis induced liver failure were mainly divided into three categories:basic and clinical research on liver failure caused by non-hepatitis B virus(HBV),the pathogenesis of HBV related liver failure,and treatment and prediction models of liver failure.The keyword time overlay map and burst map showed that the research hotspots had gradually shifted from the prevention and control of new infections to the treatment and prognosis assessment of patients with chronic infection.Conclusion China is a major international research entity in liver failure caused by viral hepatitis and actively participates in international scientific collaborations.The research hotspots on liver failure caused by viral hepatitis have gradually shifted from preventing viral hepatitis infections and expanding treatment options to the treatment of chronic infection patients and prognostic prediction.

Objective To investigate the biological effects of Pasteurella multocida(Pm)culture supernatant and Pm-derived outer membrane vesicle(OMV)on bladder cancer cells.Methods Pm was cultured and its supernatant was collected.The effects of the supernatant on proliferation,migration and invasion of bladder cancer cell lines(T24 and 5637)were assessed by cell counting kit 8(CCK-8),wound healing assay,and Transwell migration and invasion assays with phosphate-buffered saline(PBS)and brain heart infusion(BHI)broth as controls.Pm-OMV were isolated from the supernatant via ultracentrifugation,and the remaining components of the supernatant served as control.The effects of Pm-OMV on proliferation,migration and invasion of T24 and 5637 cells were assessed by CCK-8 and Transwell migration and invasion assays.Apoptosis was analyzed by flow cytometry.A nude mouse xenograft tumor model was established.After intratumoral multi-point injections of Pm-OMV or PBS,the tumor growth was evaluated and the effects of Pm-OMV on proliferation and apoptosis of bladder cancer cells in vivo were verified by Ki67(a proliferation marker)immunohistochemical staining and TUNEL assay.Results Pm culture supernatant significantly inhibited the proliferation,invasion,and migration of T24 and 5637 cells in vitro compared with PBS and BHI controls(all P＜0.01).Pm-OMV not only inhibited the proliferation,invasion,and migration of T24 and 5637 cells,but also induced the apoptosis,and the differences were significant compared with the remaining components of the supernatant(all P＜0.05).The nude mouse subcutaneous tumor transplantation experiment further confirmed that Pm-OMV inhibited the proliferation of bladder cancer cells and promoted apoptosis in vivo,and the differences were significant compared with the PBS control(all P＜0.05).Conclusion Pm-OMV can inhibit the proliferation,invasion,and migration of bladder cancer cells and promote the apoptosis.It provides an experimental basis for studying the mechanism of microbial regulation of tumor progression and for developing new treatment strategies for bladder cancer.

Objective To investigate the changes of 8 lipid biomarkers,4 complement biomarkers and albu-min(ALB)in serum of patients with colorectal cancer(CRC)and their value in CRC screening.Methods A total of 120 newly diagnosed CRC patients in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from August 2022 to January 2024 were selected as the CRC group,and 110 healthy subjects were selected as the healthy control(HC)group.A total of 8 lipid biomarkers including total cholesterol(TC),tri-glyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),apolipoprotein(Apo)A1,ApoA2,ApoB and ApoE,4 complement biomarkers including complement C3(C3),complement C4(C4),complement C1q(C1q)and complement C1 inhibitor(C1INH),3 intestinal tumor markers including carcinoembryonic antigen(CEA),carbohydrate antigen(CA)125,CA19-9,and ALB levels were detected in serum of each group.Independent sample t test and Mann-Whitney U test were used for com-parison between groups,and stepwise Fisher discriminant algorithm was used to fit each marker to establish a screening model.Receiver operating characteristic curve was used to analyze the diagnostic efficacy of each marker and the model.Results The serum levels of ApoA1,ApoA2,HDL-C,TC and ALB in CRC group were lower than those in HC group(P<0.05),while the serum levels of C1INH,C4 and CEA were higher than those in HC group(P<0.05).Among the single biomarkers,ALB had the highest diagnostic efficiency,the area under the curve(AUC)was 0.909,the sensitivity was 77.50%,and the specificity was 94.55%.The AUC of the screening model composed of ApoA2,C1INH and ALB was 0.978,the sensitivity was 91.67%,and the specificity was 98.86%.The diagnostic efficacy was higher than any single biomarker.Conclusion ApoA2,C1INH and ALB are abnormally expressed in the serum of CRC patients.The screening model composed of ApoA2,C1INH and ALB can provide reference for CRC screening and clinical auxiliary diagnosis.

Objective To investigate the diagnostic value of combined detection of serum secreted frizzled-related protein 5(SFRP5),fibroblast growth factor-21(FGF-21)and kidney injury molecule-1(KIM-1)in di-abetic nephropathy(DN).Methods Patients with DN(n=53)who were treated in Jingnan Medical District,General Hospital of the People's Liberation Army from December 2021 to December 2023 were selected as the study group,and patients with simple diabetes(n=53)were selected as the control group.The levels of ser-um SFRP5,FGF-21 and KIM-1 were detected by enzyme-linked immunosorbent assay.Multivariate Logistic regression analysis was used to analyze the factors affecting the occurrence of DN.The receiver operating char-acteristic(ROC)curve was drawn to analyze the efficacy of serum SFRP5,FGF-21 and KIM-1 levels in the di-agnosis of occurrence of DN.Results Compared with the control group,the levels of fasting blood glucose,u-rine albumin/urine creatinine,urine microalbumin,FGF-21 and KIM-1 in the study group were significantly increased(P<0.05),while the levels of glomerular filtration rate and SFRP5 were significantly decreased(P<0.05).The area under the curve(AUC)of serum SFRP5,FGF-21 and KIM-1 in the diagnosis of occur-rence of DN was 0.977,which was larger than that of each index alone(Zthree combination-SFRP5=2.759,P=0.006,Zthree combination-FGF-21=2.936,P=0.003,Zthree combination-KIM-1=3.104,P=0.002).The sensitivity of combined diagno-sis was 96.23%,the specificity was 88.68%,and the Youden index was 0.849.SFRP5,FGF-21,KIM-1,fast-ing blood glucose,glomerular filtration rate,urine albumin/urine creatinine,urine microalbumin were the in-fluencing factors of occurrence of DN(P<0.05).Conclusion The serum SFRP5 level is decreased and FGF-21 and KIM-1 levels are increased in DN patients.The combination of the three has the best diagnostic effi-ciency for occurrence of DN.

Objective:To understand the development status of maternal and child health care institutions in China from 2012 to 2022, identify the challenges they face, and provide references for further promoting the high-quality development of these institutions.Methods:Data from the China Health Statistics Yearbook (2013—2015), China Health and Family Planning Statistics Yearbook (2016—2017), and China Health and Wellness Statistics Yearbook (2018—2023) were used. Descriptive analysis was conducted on the data related to resource allocation and utilization efficiency, service provision, income and expenditure structure, and operational status of maternal and child health care institutions in China from 2012 to 2022, using methods such as fixed-base growth rate, year-on-year growth rate, and average annual growth rate. Results:From 2012 to 2022, the number of maternal and child health care institutions in China decreased from 3 044 to 3 031. In terms of resource allocation, the average annual growth rates of bed numbers and business-use floor area were 5.404% and 10.923%, respectively, while the average annual growth rate of health professionals was 7.183%. Regarding service provision, the average annual growth rates of outpatient visits and inpatient admissions were 3.954% and 1.572%, respectively. In terms of service efficiency, the bed occupancy rate decreased from 76.9% to 53.9%, and the average number of patients seen per physician per day decreased from 8.85 to 7.30. In terms of income and expenditure and operations, the income-expenditure surplus rate decreased from 9.16% to 5.41%, and the debt-to-asset ratio increased from 27.88% to 33.60%. During the same period, the average annual growth rates of bed numbers and business-use floor area in grassroots maternal and child health care institutions were 4.545% and 10.091%, respectively, lower than the national average. The number of outpatient visits increased from 89.03 million to 126.93 million, with an average annual growth rate of 3.610%, while the number of inpatient admissions decreased from 4.19 million to 3.91 million, with an average annual decline of 0.689%. The income-expenditure surplus rate of grassroots institutions decreased from 7.76% to 4.05%, 1.36 percentage points lower than the national level, and the debt-to-asset ratio increased from 27.53% to 36.37%, higher than the overall level.Conclusions:From 2012 to 2022, maternal and child health care institutions in China achieved certain developments in resource allocation and service scale. However, several challenges remain, including unbalanced resource allocation, decreased utilization efficiency, slowed growth in medical service volume, imbalanced income and expenditure structure, increased asset operation risks, and restricted development of grassroots institutions. It is recommended that relevant management departments and maternal and child health care institutions optimize resource allocation, plan for service transformation and upgrading, expand income sources, strengthen internal financial control, and reinforce the construction of high-quality and efficient maternal and child health care systems to promote the high-quality development of maternal and child health care institutions in China.