Objective: To systematically analyze the confirmatory positivity of different combinations of HBsAg screening results in blood testing, providing data to support the optimization of blood donor eligibility management. Methods: A retrospective analysis was conducted on blood screening data from 174 266 voluntary blood donor samples at the Chongqing Blood Center between October 2021 and September 2022. Samples with inconsistent results between the two HBsAg enzymelinked immunosorbent assays (ELISA) and individual donor nucleic acid testing (NAT) were confirmed using an electrochemiluminescence immunoassay (ECLIA) and a neutralization test. The detection efficacy of four different HBsAg ELISA reagents was compared using the HBsAg-confirmed positive samples. Results: A total of 767(0.44%) HBV-reactive (HB-sAg and/or HBV DNA reactive) samples were detected. Among them, 344 samples with discordant serological and NAT results were collected, of which 64(18.6%) were confirmed positive by neutralization test. Additionally, 5 samples that were neutralization-negative but double-reactive for HBsAg and HBV DNA were confirmed as positive according to FDA guidance, resulting in a total of 69(20.1%) confirmed HBsAg-positive samples. There were significant differences in the neutralization test confirmation rates among different screening result categories (P<0.05): The group with dual HBsAg reagent reactivity (double reactive) & NAT-negative had the highest confirmation rate (96.9%, 31/32); the group reactive to only reagent 2 (single reactive) had a rate of 25.7% (29/113); while the confirmation rates for samples reactive to only reagent 1 and samples with isolated HBV DNA positivity were extremely low [0(0/34) and 2.4%(4/165), respectively]. The four commercial reagents showed significant differences in their ability to detect confirmed positive samples that were initially single reactive (P<0.05). Conclusion: Given the performance variations among HBsAg screening reagents, thorough performance verification is essential before implementation. When NAT is negative, dual HBsAg reactivity in screening can serve as a basis for confirming infection and directly deferring blood donors. However, confirming infection in donors with single HBsAg reactivity is more challenging, necessitating supplementary tests to rule out infection risk.

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.

Based on the typical cases from Case Records as a Guide to Clinical Practice （《临证指南医案》） where YE Tianshi applied the "morning and evening differential treatment"， the main types are summarized as follows. When there is middle-lower interlocking injury， and yin deficiency with wind stirring， the method of restraining and consolidating in the morning can be used to restrict jueyang （厥阳）. For deficiency of the extraordinary vessels and heart-spleen ying （营） impairment， the method of consolidating should be used to raise yang in the morning， while the method of moistening and nourishing ying-yin in the evening is used. For lower jiao （焦） depletion with phlegm turbidity obstructing the orifices， it is recommended to tonify lower jiao in the morning and fortify spleen and dissolve phlegm in the evening. If there is kidney-yin depletion with dampness obstructing the qi， it is suggested to supplement kidney and improve qi reception in the morning， while purify upper jiao in the evening. For deficiency and impairment of the collateral vessels， the method of moistening and nourishing ying-yin in the evening can be used. For heart-spleen qi knot， it is recommended to dissolve phlegm and dispel stasis in the evening. In clinical practice， the same medicinal formula can be used with different methods which change according to the syndrome. Taking Sishen Pills （四神丸） and Yuhu Elixir （玉壶丹） as examples， employing different methods in accordance with the primary and secondary pathomechanisms can help transform complex， multiple pathomechanisms into organized treatment steps， providing ideas for managing complicated syndromes with modern Chinese medicine in clinical practice.

Based on the theory of diseased collaterals and the progression pattern of diabetic kidney disease （DKD）， this paper proposes a staged treatment system based on the "three states of kidney collaterals" including collateral distention， collateral bi （痹） and collateral accumulation. In the collateral distention stage， the primary pathogenesis is heat damaging the kidney collaterals and collateral vessel dilation， corresponding to the early state of DKD characterized by hyperfiltration and microalbuminuria； the clearing method is suggested， and Shenling Jiangtang Formula （参苓降糖方） can be used to promote the remission of proteinuria by ameliorating insulin resistance and regulating intestinal microecology. In the collateral bi stage， the core pathogenesis lies in the binding of phlegm and stasis， and the formation of concretions and conglomerations in the kidney collaterals， corresponding to massive proteinuria and the decline of renal function， for which the unblocking method should be taken， using Jinchan Yishen Tongluo Formula （金蝉益肾通络方） and Qingre Xiaozheng Formula （清热消癥方） to alleviate renal pathological damage by regulating the autophagy-lysosome pathway and repairing mitochondrial energy metabolism. The collateral accumulation stage is characterized by the internal retention of turbid toxins and accumulations of concretions in the kidney collaterals， corresponding to renal fibrosis and end-stage renal disease （ESRD）； the dispersion method is suggested， and Yiqi Tongluo Xiezhuo Formula （益气通络泄浊方） and Shenyan Fangshuai Fluid （肾炎防衰液） can be used to inhibit extracellular matrix accumulation and delay the progressive loss of renal function. Collateral deficiency runs through the entire course of the disease and is closely related to cellular senescence and the imbalance of the ubiquitin-proteasome/autophagy system. The concept of the "three states of kidney collaterals" integrates the evolution of traditional Chinese medicine pathogenesis with modern pathological staging， forming a whole-course intervention system of "staging-syndrome differentiation-target-formula"， thereby providing novel insights for prevention and treatment of DKD using integrated traditional Chinese and western medicine.

ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury， as well as the protective role of Huoxue Huayu Jiedu prescription （HXHYJDF） against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups： sham group， model group， deferoxamine （DFO） group （100 mg·kg^-1）， low-dose HXHYJDF group （4.52 g·kg^-1）， medium-dose HXHYJDF group （9.04 g·kg^-1）， and high-dose HXHYJDF group （18.07 g·kg^-1）， with ten rats in each group. Except for the sham group， the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1^st， 3^rd， 5^th， and 7^th days post-reperfusion using the modified neurological severity scores （m-NSS）. Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin （HE） staining and transmission electron microscopy. The contents of malondialdehyde （MDA）， glutathione （GSH）， divalent iron ions （Fe²⁺）， and reactive oxygen species （ROS） in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot （WB） were used to detect the expression of iron death marker proteins glutathione peroxidase 4 （GPX4）， ferroportin-1 （FPN1）， transferrin receptor protein 1 （TfR1）， and ferritin mitochondrial （FtMt） in brain tissue. ResultsCompared with the sham group， the mNSS score of the model group was significantly increased （P<0.01）. HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced， and the intercellular space was widened. The nucleus was fragmented， and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded， and the mitochondrial cristae decreased. The matrix was lost and vacuolated， and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS increased significantly （P<0.01）. The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased （P<0.01）， and the expression of FtMt and TfR1 proteins was significantly increased （P<0.01）. Compared with those of the model group， the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3^rd and 5^th days， respectively （P<0.05， P<0.01）. The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly （P<0.01）， and the contents of MDA， Fe²⁺， and ROS decreased significantly （P<0.05， P<0.01）. The content of GSH in the low-dose HXHYJDF group increased significantly （P<0.01）， and the contents of MDA and ROS decreased significantly （P<0.01）. The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly （P<0.01）， and the expression of FtMt and TfR1 decreased significantly （P<0.01）. The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly （P<0.05）， and the expression of TfR1 decreased significantly （P<0.01）. WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose， medium-dose， and low-dose HXHYJDF groups were significantly up-regulated （P<0.01）， and the expression levels of FtMt and TfR1 proteins were significantly down-regulated （P<0.01）. ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury， improve the pathological morphology of the infarcted brain tissue， and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury， with increased levels of MDA， Fe²⁺， ROS， and TfR1 and decreased levels of FtMt， FPN1， GPX4， and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins， promoting the discharge of free iron， reducing brain iron deposition， alleviating oxidative stress， and inhibiting ferroptosis.

In recent years, cancer treatment methods and means are becoming more and more diversified, and single treatment methods often have limited efficacy, while the synergistic effect of immunity combined with chemotherapy can inhibit tumor growth more effectively. Based on this, we constructed a sodium alginate hydrogel composite system loaded with chemotherapeutic agents and tumor vaccines (named SA-DOX-NA) with a view to the combined use of chemotherapeutic agents and tumor vaccines. Firstly, the tumor vaccine (named NA) degradable under acidic conditions was constructed by in situ polymerization using chicken ovalbumin (OVA), acrylamide (AAM) and 2-(dimethylamino) ethyl methacrylate (DMAEMA) monomer. Then a hydrogel composite system SA-DOX-NA co-loaded with chemotherapeutic drug doxorubicin (DOX) and NA was prepared using sodium alginate as a matrix. The results showed that SA-DOX-NA had good in situ gel-forming ability and formed a mesh structure that could realize the co-loading of DOX and NA as well as the slow drug release. The electron microscopy results showed that SA-DOX-NA had good in situ gel-forming ability with good internal connectivity, and the three-dimensional mesh structure could realize the co-loading of DOX and NA as well as the slow drug release. The antitumor and immunomodulatory results showed that SA-DOX-NA both effectively inhibited the growth of tumor cells and efficiently promoted the proliferation and activation of DC2.4 dendritic cells without additional adjuvant. In summary, SA-DOX-NA exerts the dual efficacy of chemotherapy and immunotherapy for tumor treatment, and has a good application prospect in local tumor treatment.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective:To investigate the effect of microRNA-363-5p targeted binding to THBS3 on angiotensin Ⅱ-induced apoptosis in cardiomyocytes and its molecular mechanism.Methods:A human-derived cardiomyocyte cell line(AC16)was used to establish an in vitro cardiomyocyte apoptosis model with angiotensin Ⅱ(AngⅡ),and a dual luciferase reporter assay was performed to detect the relationship between miR-363-5p and THBS3;apoptosis rate was detected by flow cytometry,and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was performed to detect the relative expression of microR-363-5p,ATF-6mRNA,THBS3mRNA expression;Western Blot to detect the relative expression of caspase-12,caspase-3,GRP78,Bax,Bcl-2.Results:(1)Compared with the control group,the relative expression level of miR-363-5p in AngⅡ group was significantly decreased.(2)Compared with Mir-inhibitor-NC and Mir-mimics-NC groups,the apoptosis rate of miR-inhibitor and miR-mimics groups was significantly increased and decreased,the relative expression level of Bax protein was significantly increased and decreased,and the relative expression level of Bcl-2 was decreased and increased.(3)miR-363-5p targeted binding to THBS3.(4)Compared with the THBS3-OENC group,the relative expression of Bax and caspase-3 proteins was significantly higher,the relative expression of Bcl-2 protein was significantly lower,and the apoptosis rate was higher in the THBS3-OE group.(5)Compared with the negative control group,the relative expression of Bax and caspase-3 proteins in the miR-mimcs+THBS3-OE group was significantly higher,the relative expression of Bcl-2 protein was significantly lower,the apoptosis rate was significantly higher,and the cell viability was significantly lower.(6)Compared with the miR-inhibitor group,the relative expression of GRP78 and caspase-12 was decreased in the miR-inhibitor-4-PBA group,and the apoptosis rate was significantly reduced.(7)Compared with the negative control group,the apoptosis rate was elevated in the ATF-6-OE group,and the relative expression of caspase-12 was significantly increased.(8)Compared with the negative control group,miR-inhibitor+ATF-6 siRNA group showed decreased apoptosis rate and decreased relative expression of caspase-12.Conclusions:MicroRNA-363-5p is able to target binding to THBS3 to regulate myocardial apoptosis,a process that may be mediated through the endoplasmic reticulum stress ATF-6 pathway.

Objective To investigate the predictive value of atherosclerotic index of plasma(AIP)for the risk of coronary heart disease(CHD)in patients with nonalcoholic fatty liver disease(NAFLD).Methods A retrospective analysis was conducted in 299 patients with NAFLD.Based on presence or absence of CHD,the patients were divided into NAFLD with CHD group(n=177)and NAFLD group(n=122).Clinical data were collected from both groups,and AIP was calculat-ed.Multivariate Logistic regression analysis was performed to explore the independent risk factors for CHD in patients with NAFLD.Receiver operating characteristic(ROC)curves were plotted to evalu-ate the predictive value of AIP for the risk of CHD in patients with NAFLD.Results The NAFLD with CHD group had a higher proportion of males,smokers,and higher levels of alanine aminotrans-ferase(ALT),aspartate aminotransferase(AST),fasting plasma glucose(FPG),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),γ-glutamyltransferase(GGT),uric acid(UA),and AIP than the NAFLD group.The NAFLD with CHD group also had lower levels of high-density lipoprotein cholesterol(HDL-C)than the NAFLD group(P＜0.05).Multivariate Logistic regression analysis revealed that males(OR=2.548,95％CI,1.402 to 4.632,P=0.002),high levels of AST(OR=1.038,95％CI,1.002 to 1.077,P=0.041),high levels of LDL-C(OR=1.811,95％CI,1.242 to 2.640,P=0.002),and high AIP(OR=16.117,95％CI,1.874 to 138.609,P=0.011)were independent risk factors for CHD in patients with NAFLD(P＜0.05).ROC curve analysis showed that AIP had an area under the curve of 0.746(95％CI,0.688 to 0.804)for pre-dicting CHD in patients with NAFLD,with a sensitivity of 76.3％and a specificity of 73.0％.Conclusion AIP is an independent influencing factor for CHD in patients with NAFLD and has certain predictive value for the risk of CHD in these patients.