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.

Objective To explore the mechanisms of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in improvement of renal injury in rats with diabetic nephropathy (DN) by regulating mammalian target of rapamycin (mTOR)/p70 ribosome protein S6 kinase (S6K1)/coiled-coil myosin-like Bcl-2-interacting protein (Beclin 1) pathway. Methods The model of SD rats with DN was established by a method of high-fat diet combined with intraperitoneal injection of streptozotocin, and they were randomly divided into model group, MSC-EVs group, and MSC-EVs+MHY1485 (mTOR activator) group, with 12 rats in each group. Another 12 SD rats were normally fed for 6 weeks and then intraperitoneally injected with an equal dose of sodium citrate solution as controls. After grouping with MSC-EVs and MHY1485, blood glucose and levels of renal function indicators [blood urea nitrogen (BUN), serum creatinine (Scr), and urinary microalbumin (UmALB)] in rats were detected. HE staining was used to detect the pathological morphology of renal tissue in rats of each group; immunohistochemistry was used to detect the expression of mTOR/S6K1/Beclin 1 pathway related proteins in the renal tissues of rats in each group; the Western blot was used to detect the mTOR/S6K1/Beclin 1 pathway and autophagy-related protein expression in the renal tissues of rats in each group. Results Compared with the control group, the renal tissue morphology of rats in the model group were impaired, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, p-S6K1/S6K1 increased significantly (P < 0.05), while microtubule associated protein 1A/1B light chain 3 (LC3) Ⅱ/LC3Ⅰ, expression of Beclin 1 protein, and relative positive expression of Beclin 1 significantly reduced (P < 0.05); compared with the model group, the MSC-EVs group had less impairment in the renal tissue morphology, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, p-mTOR/mTOR, and p-S6K1/S6K1 decreased significantly (P < 0.05), while expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 increased significantly (P < 0.05); compared with the MSC-EVs group, the impairment of the renal tissue morphology was worse in the MSC-EVs+MHY1485 group, and the blood glucose, BUN, Scr, UmALB, relative positive expressions of p-mTOR and p-S6K1, expression of p-mTOR/mTOR, and p-S6K1/S6K1 increased significantly (P < 0.05), while the expression of LC3Ⅱ/LC3Ⅰ, Beclin 1 protein, and relative positive expression of Beclin 1 decreased significantly (P < 0.05). Conclusion MSC-EVs can enhance autophagy, reduce levels of blood glucose, Scr, BUN and urinary protein in rats with DN, alleviate renal tissue damage, and the mechanism may be achieved by inhibiting the activation of the mTOR/S6K1/Beclin 1 pathway.

Objective To investigate the effect of γ-aminobutyric acid(GABA)signaling pathway on endoplasmic reticulum(ER)stress and mitochondrial autophagy in septic rats with acute lung injury(ALI).Methods SD rats were randomly grouped into the control(CON)group,the model group,the GABA signaling pathway activator Baclofen group(the Baclofen group),the GABA signaling pathway inhibitor dicentrine group(the BIC group),with 6 rats in each group.The Baclofen group received intraperitoneal injection of 5 mg/kg Baclofen,and the BIC group received intraperitoneal injection of 1 mg/kg BIC,once a day,for two consecutive weeks.The CON group and the model group were injected with an equal amount of physiological saline via intraperitoneal injection.Enzyme linked immunosorbent assay was applied to detect serum levels of superoxide dismutase(SOD)and malondialdehyde(MDA)and levels of cytochrome C(Cyt.C)and Nicotinamide adenine dinucleotide phosphate(NADPH)in bronchoalveolar lavage fluid(BALF).Transmission electron microscopy(TEM)was applied to observe the ultrastructure of lung tissue cells.HE staining was applied to observe the pathological morphology of lung tissue.TUNEL staining was applied to observe the apoptosis of lung tissue.Western blot assay was applied to detect expression levels of GABAAR,GRP78 and CHOP proteins in lung tissue.Results Compared with the model group,the lung swelling,congestion and inflammatory cell infiltration were improved in the Baclofen group,and the lung injury score,MDA content,apoptosis index,Cyt.C and NADPH levels,GRP78,and CHOP protein levels were reduced(P＜0.05).The number of autophagic vacuoles in phagocytic mitochondria,SOD content and GABAAR protein level were increased(P＜0.05),however,the trend of above indicators in the BIC group was opposite to that in the Baclofen group.Conclusion Up-regulation of GABA signaling pathway may have an improvement effect on ALI in sepsis rats.

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Objective To investigate the distribution and antimicrobial resistance of bacterial isolates from blood samples in the hospitals participating in China Antimicrobial Surveillance Network (CHINET) from 2015 to 2021.Methods Bacterial strains isolated from blood samples were collected from 52 medical centers participating in CHINET from 2015 to 2021 for analysis of bacetrial distribution and antimicrobial resistance.Results A total of 153591 isolates were collected,48.8％ of which were gram-positive bacteria and 51.2％ were gram-negative bacteria.The top five bacterial strains were coagulase negative Staphylococcus (28.2％),Escherichia coli (20.7％),Klebsiella (13.7％),Enterococcus (7.2％),and Staphylococcus aureus (6.6％).Compard to female patients,male patients showed lower proportion of E.coli and higher proportions of other bacterial species in all the bacterial isolaets from blood samples.The proportions of Streptococcus pneumoniae and Salmonella in all the bacterial isolaets from blood samples were higher in children compared to adults.Enterobacterales species showed various resistance rates to antimicrobial agents.Overall,≥58.0％,≥36.8％ and ≥56.8％ of E.coli strains were resistant to cefotaxime,gentamicin and levofloxacin respectively over the 7-year period.However,less than 2.5％ of the E.coli strains were resistant to carbapenems.K.pneumoniae showed higher resistance rates to imipenem and meropenem than other Enterobacterales species.During the 7-year period,the prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae increased from 21.4％ and 19.9％ in 2015 to 25.7％ and 26.6％ in 2021,respectively.However,carbapenems still maintained good antibacterial activity against other Enterobacterales,associaetd with lower resistance rates.In the 7-year period,Acinetobacter baumannii showed a dwonward trend in the resistance rates to imipenem and meropenem,but remained 72.9％ and 73.2％ respectively in 2021.The prevalence of imipenem-resistant and meropenem-resistant P.aeruginosa decreased from 26.7％ and 22.9％ in 2015 to 18.5％ and 14.7％ in 2021,respectively.The prevalence of PRSP was 1.5％ in the isolaets from adults and and 0.8％ in the isolates from children.Less than 3.0％ of the Enterococcus faecium and Enterococcus faecalis strains were resistant to vancomycin,teicolanin,or linezolid.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase negative Staphylococcus (MRCNS) was 32.1％ and 81.0％,respectively.The prevalence of MRSA was relatively stable,28.5％ in 2015 and 28.0％ in 2021.Conclusions Coagulase negative Staphylococcus,E.coli and K.pneumoniae were the main bacterial species isolated from blood samples in the hospitals participaing in the CHINET from 2015 to 2021.Significant sex and age differences were found in the distribution of bcterial isolates from blood samples.The overall resistance rates of the top bacetrial strains from blood samples to antimicrobial agents showed a downward trend.Ongoing surveillance of antimicrobial resistance for the isolates from blood samples is still essential for prescribing rational antimicrobial therapies and curbing bacterial resistance.

Objective To investigate the distribution and antimicrobial resistance of bacterial isolates from blood samples in the hospitals participating in China Antimicrobial Surveillance Network (CHINET) from 2015 to 2021.Methods Bacterial strains isolated from blood samples were collected from 52 medical centers participating in CHINET from 2015 to 2021 for analysis of bacetrial distribution and antimicrobial resistance.Results A total of 153591 isolates were collected,48.8％ of which were gram-positive bacteria and 51.2％ were gram-negative bacteria.The top five bacterial strains were coagulase negative Staphylococcus (28.2％),Escherichia coli (20.7％),Klebsiella (13.7％),Enterococcus (7.2％),and Staphylococcus aureus (6.6％).Compard to female patients,male patients showed lower proportion of E.coli and higher proportions of other bacterial species in all the bacterial isolaets from blood samples.The proportions of Streptococcus pneumoniae and Salmonella in all the bacterial isolaets from blood samples were higher in children compared to adults.Enterobacterales species showed various resistance rates to antimicrobial agents.Overall,≥58.0％,≥36.8％ and ≥56.8％ of E.coli strains were resistant to cefotaxime,gentamicin and levofloxacin respectively over the 7-year period.However,less than 2.5％ of the E.coli strains were resistant to carbapenems.K.pneumoniae showed higher resistance rates to imipenem and meropenem than other Enterobacterales species.During the 7-year period,the prevalence of imipenem-resistant and meropenem-resistant K.pneumoniae increased from 21.4％ and 19.9％ in 2015 to 25.7％ and 26.6％ in 2021,respectively.However,carbapenems still maintained good antibacterial activity against other Enterobacterales,associaetd with lower resistance rates.In the 7-year period,Acinetobacter baumannii showed a dwonward trend in the resistance rates to imipenem and meropenem,but remained 72.9％ and 73.2％ respectively in 2021.The prevalence of imipenem-resistant and meropenem-resistant P.aeruginosa decreased from 26.7％ and 22.9％ in 2015 to 18.5％ and 14.7％ in 2021,respectively.The prevalence of PRSP was 1.5％ in the isolaets from adults and and 0.8％ in the isolates from children.Less than 3.0％ of the Enterococcus faecium and Enterococcus faecalis strains were resistant to vancomycin,teicolanin,or linezolid.The prevalence of methicillin-resistant S.aureus (MRSA) and coagulase negative Staphylococcus (MRCNS) was 32.1％ and 81.0％,respectively.The prevalence of MRSA was relatively stable,28.5％ in 2015 and 28.0％ in 2021.Conclusions Coagulase negative Staphylococcus,E.coli and K.pneumoniae were the main bacterial species isolated from blood samples in the hospitals participaing in the CHINET from 2015 to 2021.Significant sex and age differences were found in the distribution of bcterial isolates from blood samples.The overall resistance rates of the top bacetrial strains from blood samples to antimicrobial agents showed a downward trend.Ongoing surveillance of antimicrobial resistance for the isolates from blood samples is still essential for prescribing rational antimicrobial therapies and curbing bacterial resistance.

Objective: To investigate the effect of silencing the endoplasmic reticulum stress-related protein calnexin on the proliferation, invasion, and migration of tongue squamous cell carcinoma cells. Methods : Calnexin siRNA was transfected into SCC-9 and SCC-25 tongue squamous cell carcinoma cells, and the expression of calnexin was detected by qRT-PCR. The silencing effect of calnexin siRNA was further verified by Western blotting. CCK-8 assay was applied to detect the effect of silencing calnexin on the proliferation of tongue squamous cell carcinoma cells; Transwell assay was used to detect the effect of silencing calnexin on the invasion and migration of tongue squamous cell carcinoma cells. Results : qRT-PCR showed that calnexin siRNA could effectively downregulate the expression of calnexin. Western blot analysis further confirmed the silencing effect of calnexin siRNA on calnexin. The CCK-8 assay showed that silencing calnexin expression on the 4th and 5th days could inhibit the proliferation of tongue squamous cell carcinoma cells, and the difference was statistically significant (P < 0.01). The Transwell assay showed that knockdown of calnexin could inhibit the invasion and migration of tongue squamous cell carcinoma cells (P < 0.001). Conclusion Knockdown of calnexin can inhibit the proliferation, invasion, and migration of tongue squamous cell carcinoma cells.

Multi-species solid-state fermentation in a mud pit is one of the typical features of strong-flavor baijiu, in which archaea plays important roles, however, the archaeal community distribution and diversity during fermentation are still lack of research. The biomass, composition and succession of archaea communities in fermented grains and pit mud were analyzed by high throughput sequencing. The potential interaction between archaea and bacteria was analyzed by co-occurrence network. Results demonstrate that the average biomass of archaea in pit mud was about 200 times higher than that of fermented grains. There was no significant difference in archaeal community structure between fermented grains and pit mud (r=0.017, P=0.074), but succession patterns between them showed significant correlation (r=0.30, P=0.03). Methanobacterium was the most abundant archaea in fermented grains and pit mud, and other dominant groups included Methanosarcina, Methanocorpusculum, Methanoculleus, and Methanobrevibacter. The co-occurrence network analysis showed that Methanobacterium was positively correlated with most bacteria in fermented grains and pit mud, especially with Hydrogenispora and Caproiciproducens, the dominant bacteria in pit mud. Our results revealed the temporal and spatial distribution characteristics and potential functions of the archaeal community in the mud pit of strong-flavor baijiu.
Alcoholic Beverages/analysis* ; Archaea/genetics* ; Bacteria ; Fermentation ; Taste

Objective To investigate the clinical efficacy of Kirschner wire,reconstruction plate and locking compression plate internal fixation in the treatment of Robinson type 2A and 2B midshaft clavicle fracture.Methods One hundred and fifty patients with midshaft clavicle fracture in the hospital from August 2006 to August 2015 were selected and divided into the group A,B and C.The group A adopted Kirschner wire,group B adopted the reconstruction plate and group C adopted the locking compression plate internal fixation.Then the incision length,operative time,intraoperative blood loss,fracture healing time,postoperative Constant-Murley scores and DASH scores and postoperative complications incidence rate were compared among the three groups.Results The incision length,operative time and intraoperative blood loss in the group A and C were significantly better than those in the group B(P＜0.05).The fracture healing time,postoperative activity,muscle strength and daily life score,postoperative complications incidence rate,postoperative DASH score in the group C were significantly better than those in the group A and B(P＜0.05).Conclusion The locking compression plate in the treatment of Robinson type 2A and 2B midshaft clavicle fracture can effectively reduce the surgical trauma,shortens the fracture healing time and decreases the postoperative complications.

Objective To evaluate the efficacy of rescue treatment for recurrent esophageal cancer after radical esophagectomy, and to provide insights into the development of comprehensive treatment for esophageal cancer.Methods The clinical data of 218 patients who were confirmed with recurrent metastatic esophageal cancer after R0 resection and received rescue treatment in our hospital from 2004 to 2014 were retrospectively reviewed.The survival rate was determined by the Kaplan-Meier method.Univariate and multivariate prognostic analyses were performed using the log-rank test and Cox proportional hazards model, respectively.Results The median post-recurrence follow-up time was 53 months.The 1-and 3-year overall survival (OS) rates after recurrence were 57.2% and 24.4%, respectively.Among the 163 patients with local recurrence, the 1-and 3-year OS rates were 70% and 42% for patients treated with chemoradiotherapy (n=40), 55% and 24% for those with radiotherapy alone (n=106), and 23% and 8% for those with supportive therapy (n=13)(chemoradiotherapy vs.radiotherapy alone P=0.045, radiotherapy alone vs.supportive therapy P=0.004;none of the patients who were treated with chemotherapy alone survived for one year or more).Univariate analysis showed that N staging, TNM staging, and post-recurrence rescue treatment regimen were independent prognostic factors for esophageal cancer (all P=0.001).On the other hand, multivariate analysis indicated that only rescue treatment regimen was the independent prognostic factor for esophageal cancer (P=0.013).Conclusions Rescue chemoradiotherapy or radiotherapy alone can bring significant survival benefits for patients with recurrent and metastatic, especially locally recurrent, esophageal cancer following radical esophagectomy.