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.

ObjectiveThe widespread adoption of portable fundus cameras for primary care and community screening is hindered by limitations in current autofocus(AF) technologies. Image-based methods relying on sharpness evaluation require iterative searches, resulting in slow convergence, while projection-based techniques are susceptible to optical artifacts and calibration errors. To address these challenges, this study introduces a novel AF system based on direct wavefront sensing, designed to deliver simultaneous high speed, high precision, and operational robustness within the compact form factor essential for portable ophthalmic devices. MethodsOur approach fundamentally reimagines the AF process by directly measuring the ocular wavefront aberration. We developed a custom portable fundus camera integrating a miniaturized Shack-Hartmann wavefront sensor (SHWS) into the optical path. An 850 nm laser diode projects a point source onto the retina via oblique illumination to minimize corneal reflections. Light scattered from this spot carries the eye’s refractive error through the imaging optics and is directed to the SHWS, positioned at a plane optically conjugate to the primary color CMOS imaging sensor. A microlens array within the SHWS samples the incident wavefront, generating a pattern of focal spots on a CCD. Real-time centroid analysis of these spots provides a map of local wavefront slopes. These measurements are processed through a singular value decomposition (SVD) algorithm to fit a Zernike polynomial basis set, enabling real-time reconstruction of the wavefront phase. The defocus component (S) is extracted from the second-order Zernike coefficients, providing a direct, quantitative measure of the refractive error in diopters. This value serves as a precise error signal in a closed-loop control system, which commands a voice-coil actuated focusing lens to its null position in a single, deterministic step, eliminating the need for iterative search algorithms. ResultsComprehensive evaluation demonstrated the system’s high performance. Testing on a calibrated model eye (OEMI-7) established a highly linear relationship between the computed defocus S and the focusing lens position across a ±20 Diopter (D) compensation range, achievable within a 5 mm mechanical travel. The system achieved a focusing precision of 0.08 D, corresponding to an 18-fold improvement over a conventional projection spot-size method tested under identical conditions. The total focus acquisition time, encompassing wavefront measurement, computation, and lens actuation, averaged under 0.5 s. Clinical validation with 25 human volunteers (50 eyes, refractive range -15 D to +10 D) confirmed practical efficacy. The wavefront-sensing AF succeeded in 92% of attempts with a mean time of 0.5 s, substantially outperforming a projection-based benchmark which achieved only a 32% success rate with an average time of 4.25 s. The system provided instantaneous directional guidance and maintained stability during minor ocular movements. Objective assessment of image quality, via amplitude contrast of retinal vasculature, showed consistent and significant enhancement following AF correction across the entire tested diopter range. ConclusionThis work successfully implements and validates a direct wavefront-sensing autofocus paradigm for portable fundus cameras. By directly quantifying and compensating for the optical defocus aberration, this method bypasses the fundamental limitations of image-processing and projection-based techniques, enabling rapid, precise, and deterministic diopter compensation. The developed system delivers an exceptional combination of a wide operational range (±20 D), high accuracy (0.08 D), fast convergence (0.5 s), and a compact physical footprint. This technology provides a practical and high-performance focusing solution capable of enhancing the reliability, throughput, and diagnostic utility of portable retinal imaging in large-scale screening applications. Future efforts will be directed towards system cost optimization and performance adaptation for diverse ocular conditions.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.

Objective To investigate the potential beneficial predictors for endovascular treatment(EVT)in case of acute anterior circulation large vessel occlusion with large-core infarction.Methods We made a retrospective inclusion of 92 patients with anterior circulation large vessel occlusion and core infarct volume ranging from 50 to 100 mL,who underwent EVT at Zhangzhou Municipal Hospital of Fujian Province from March 2018 to February 2021.All the patients were confirmed as anterior circulation large infarction and large infarct volume using computed tomography(CT),computed tomography angiography(CTA),and computed tomography perfusion(CTP)before EVT.All clinical and imaging data were collected to observe the postoperative recurrence rate,incidence of symptomatic intracranial hemorrhage(sICH),and functional prognosis 90 days.Then the patients were divided into favorable outcomes group(mRS≤3)and unfavorable outcomes group(mRS＞3)based on Rankin scores 90 days post-stroke.Univariate and multivariate Logistic analysis were conducted to analyze factors influencing the patients'prognosis.By combining the results of multivariate analysis,we constructed receiver operating characteristic(ROC)curves and identified the cut-off value to evaluate the predictive value of age for post-vascular treatment prognosis.Results Among the included patients,the postoperative revascularization rate(mTIICI≥2b)was 95％(88 cases),the rate of favorable outcomes at 90 days postoperatively(mRS≤3)was 32.61％(30 cases),the incidence of sICH was 13％,and the mortality rate was 31.5％.Compared with the unfavorable outcomes group,the favorable outcomes group had a younger age and a higher proportion of males.Multivariate analysis indicated that older age was an independent risk factor for adverse outcomes following endovascular treatment(OR=4.97,95％CI:1.78-13.90,P=0.002).The ROC curve indicated that the area under the curve was maximized at the age of 72.5 years(AUC=0.763,95％CI:0.661-0.864,P＜0.001).Its sensitivity and specificity was 0.565 and 0.833,respectively.Conclusion Age is an independent predictor of the prognosis of acute procirculatory large core stroke.Patients with large core infarction older than 72.5 years may not benefit from endovascular therapy,which needs to be confirmed by a multicenter large sample prospective randomized controlled trial.

Objective:This study aims to investigate the expression of uridine diphosphate-glucose[]pyrophos-phorylase 2(UGP2)in breast cancer(BC)tissues and its oncogenic mechanism,assessing its potential value as a diag-nostic and prognostic biomarker for breast cancer.Methods:(1)Online database analysis was conducted to assess UGP2 mRNA and protein expression levels in breast cancer and explore their correlation with clinical characteristics.Im-munohistochemistry(IHC)was used to verify UGP2 expression in human breast cancer tumor tissues and evaluate its relationship with clinicopathological features.(2)Kaplan-Meier survival analysis and COX regression models were used to analyze the impact of UGP2 expression on breast cancer patient prognosis.(3)Bioinformatics methods were em-ployed to investigate the correlation between UGP2 and tumor immune cell infiltration,and to predict the biological func-tions and associated signaling pathways of UGP2 in breast cancer.Results:(1)The mRNA and protein expression levels of UGP2 were upregulated in breast cancer tissues(both P<0.05),and were negatively correlated with ER-positive and PR-positive status(OR<1,P<0.05),while positively correlated with Ki-67 levels and the triple-negative breast cancer(TNBC)subtype(OR>1,P<0.05).(2)Elevated expression levels of UGP2 were associated with poorer survival rates in breast cancer patients(both P<0.05)and were identified as an independent adverse prognostic factor for breast cancer(HR=1.40,P<0.05).(3)Functional analysis results suggested that UGP2 may promote tumor progression by regulating metabolism,hormone signaling,and the immune microenvironment.Additionally,UGP2 expression was negatively cor-related with NK cell activation status and positively correlated with the inhibitory state.Conclusion:UGP2 expression is elevated in breast cancer tissues and is closely associated with poor patient prognosis.It may promote cancer pro-gression through mechanisms such as metabolic reprogramming and immune suppression.UGP2 shows promise as a potential biomarker and therapeutic target in breast cancer,providing a basis for personalized treatment.

Objective To investigate the effects of meridian and tendon acupuncture on the mitochondrial apoptosis of quadriceps femoris muscle cells in model rats of knee osteoarthritis(KOA);To explore its mechanism for the treatment of KOA.Methods Totally 40 SPF healthy male Wistar rats were randomly divided into sham-operation group(10 rats)and modeling group(30 rats).The modified Hulth method was used to establish a KOA rat model.The model rats were randomly divided into model group,celecoxib group and meridian and tendon acupuncture group,with 9 rats in each group.Corresponding intervention measures were given to each group for 14 consecutive days.Improved Lequesne MG score was used for evaluating knee joint function in rats,measuring thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate and wet weight ratio of the affected limb,HE staining was used to observe the morphology of quadriceps femoris tissue,TUNEL method was used to detect apoptosis of quadriceps femoris cells,immunofluorescence was used to detect the expressions of reactive oxygen species(ROS),superoxide dismutase(SOD),Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue,fluorescence double staining method was used to detect the co-expression of ROS and Caspase-3 in quadriceps femoris tissue,Western blot was used to detect the expressions of apoptosis related proteins in quadriceps femoris tissue.Results Compared with the sham-operation group,the improved Lequesne MG score of the knee joint in the model group rats increased(P<0.05),the circumference of the thigh,wet weight of the quadriceps femoris,wet weight maintenance rate and wet weight ratio of the affected limb decreased(P<0.05),the arrangement of quadriceps femoris muscle fibers was disordered and loose,with some muscle fibers dissolved and necrotic,accompanied by a large amount of inflammatory exudate,an increase in lymphocytes,and an increase in cell apoptosis index(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue increased,while the expression of SOD decreased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,Cytochrome C(CytC),Caspase-3 and Caspase-9 in quadriceps femoris tissue increased(P<0.05).Compared with the model group,the improved Lequesne MG scores of the knee joint in the celecoxib group and the meridian and tendon acupuncture group decreased(P<0.05),while thigh circumference,quadriceps femoris wet weight,wet weight maintenance rate,wet weight ratio increased(P<0.05),the structure of quadriceps femoris muscle fibers was normal,the muscle membrane was relatively intact,the apoptosis index decreased(P<0.05),the expressions of ROS,Caspase-3 and Caspase-9 in quadriceps femoris tissue decreased,while the expression of SOD increased(P<0.05),the protein expressions of Bcl-2,Bcl-XL,Bax,CytC,Caspase-3 and Caspase-9 in quadriceps femoris muscle tissue decreased(P<0.05),and the expression trend of ROS and Caspase-3 in fluorescent double staining was consistent.Conclusion Meridian and tendon acupuncture can reduce ROS in the quadriceps femoris tissue of KOA model rats,inhibit the expressions of mitochondrial apoptosis-related proteins,thereby improving skeletal muscle strength,and play a certain therapeutic role.

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 explore the mechanism of acupuncture protection of quadriceps muscle cells in knee osteoarthritis model rats based on Piezo1/YAP/Caspase3 axis.Methods 40 SPF grade Wistar rats were selected and adaptively fed for 7 days before being divided into three groups:sham surgery group,model group,western medicine group,and acupuncture group,with 10 rats in each group,according to a random control table.The model group,Western medicine group,and acupuncture group used the modified Hulth method to construct knee osteoarthritis models,while the sham surgery group only cut open the joint cavity and sutured it.After successful model replication,the sham surgery group was given physiological saline by gavage,the western medicine group was given celecoxib solution by gavage,and the acupuncture group was given acupuncture at the infrapatellar,crane top,and blood sea levels.Each group was intervened once a day for 14 consecutive days.During the treatment period,the rats continued to undergo treadmill training.After the intervention,the hematoxylin eosin staining method(HE)was used to detect the morphological changes of various rat quadriceps muscle tissues and articular cartilage;TUNEL method was used to detect apoptosis of quadriceps muscle cells,immunofluorescence method was used to detect the protein expression of Piezo1,YAP,and p-YAP in quadriceps muscle cells,Western blot method was used to detect the expression of anti apoptotic proteins CTGF,AREG,Gli2,AFP in quadriceps muscle tissue,as well as the protein expression levels of apoptosis related proteins Bcl-2,Bcl-xl,Bax,cytc,and Caspase3.Results Compared with the model group,the western medicine group and the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the western medicine group,the acupuncture group had higher thigh circumference,quadriceps wet weight,wet weight maintenance rate,and wet weight to body weight ratio(P<0.05).Compared with the model group,the apoptosis index of the quadriceps muscle in the Western medicine group and acupuncture group rats was lower,and the apoptosis index of the quadriceps muscle in the acupuncture group was lower(P<0.05).Compared with the model group,the Western medicine group and acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps femoris muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Compared with the Western medicine group,the acupuncture group showed higher expression of Piezo1 and p-YAP proteins in the quadriceps muscle tissue,lower expression of YAP protein,higher expression of CTGF,AREG,Gli2,AFP proteins,higher expression of Bcl-2 and Bcl-xl proteins,and lower expression of Bax,cytc,and Caspase3 proteins(P<0.05).Conclusion Acupuncture increases the expression of Piezo1 protein in the quadriceps femoris muscle of knee osteoarthritis model rats,promotes the phosphorylation of YAP into the nucleus,thereby promoting proliferation,anti apoptotic proteins CTGF,AREG,Gli2,and AFP protein expression,inhibiting Caspase3-dependent mitochondrial apoptosis,and protecting muscle cells.