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.

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

AIM: To evaluate the surgical outcomes and changes in the ocular surface microenvironment following radiofrequency minimally invasive treatment for conjunctivochalasis-induced epiphora.METHODS: Patients with epiphora primarily caused by conjunctivochalasis were enrolled. All patients had conjunctivochalasis of ≥grade II, and their symptoms showed no significant improvement after previous pharmacological treatment. All patients underwent radiofrequency minimally invasive correction of conjunctivochalasis, supplemented with artificial tears, anti-inflammatory therapy, and ocular surface repair treatment postoperatively. At 8 wk post-surgery, the ocular surface disease index(OSDI), eye redness, tear secretion, non-invasive tear break-up time, lipid layer thickness, tear ferning test, and conjunctival impression cytology were assessed to compare treatment efficacy and observe changes in the ocular surface microenvironment.RESULTS: A total of 43 cases(43 eyes)of conjunctivochalasis and with a main complaint of epiphora were included, including 23 males and 20 males, with a mean age of 64.69±3.36 years. The total effective rate of surgery was 91% at 8 wk postoperatively. Compared with preoperative values, the OSDI scores significantly decreased and the non-invasive tear break-up time was prolonged at 8 wk post-surgery(all P<0.05). No statistically significant differences were observed in lipid layer thickness or tear secretion at 8 wk postoperatively(all P>0.05). The normal rate of chloramphenicol taste test increased from 21% preoperatively to 63% postoperatively; the normal rate of eye redness increased from 40% to 70%; normal rate of tear ferning grading improved from 30% to 63%; and normal conjunctival impression cytology grading increased from 21% to 74%.CONCLUSION: Radiofrequency minimally invasive treatment is effective for conjunctivochalasis and is straightforward to perform. Patients with conjunctivochalasis often present with other ocular surface issues beyond conjunctivochalasis itself, such as insufficient tear secretion, reduced lipid layer thickness, and other dry eye-related problems. Therefore, a comprehensive approach emphasizing tear dynamics should be adopted during treatment.

ObjectiveTo investigate the mechanism by which Notoginsenoside R1 （NGR1） ameliorates hypoxia/reoxygenation （H/R）-induced injury in AC16 human cardiomyocyte cell lines through the regulation of mitophagy. MethodsCommon genes linked to hypoxia/reoxygenation injury and mitophagy were identified by intersecting data from GeneCards and MitoCarta databases. AC16 cell viability was assessed via CCK-8 assay under varying NGR1 concentrations （0， 6.25， 12.5， 25， 50， 100， 200， 300， 400， 500 μmol/L）. AC16 cells were divided into the following groups： control group （Control）， model group （H/R）， and treatment groups （H/R + NGR1 at 100， 200 and 300 μmol/L）. Mitochondrial membrane potential （ΔΨm） was measured using 5，5'，6，6'-tetrachloro-1，1'，3，3'-tetraethylbenzimidazolylcarbocyanine iodide （JC-1） staining. Transcriptional levels of mitophagy-related genes （Parkin， Pink1， P62） were quantified by reverse transcription-quantitative PCR （RT-qPCR）. Protein expression of mitophagy-related markers （Parkin， Pink1， P62， and LC3BⅡ） was evaluated via Western blot analysis. Mitochondrial ultrastructure was visualized by transmission electron microscopy （TEM）. ResultsCompared to the control group， cell viability in the H/R group significantly decreased （P<0.01）. Treatment with NGR1 at concentrations above 100 μmol/L significantly enhanced the cell viability of AC16 cells compared to the H/R group （P<0.01）. H/R induced a significant decrease in mitochondrial membrane potential （P<0.01）， which was restored by NGR1 treatment （P<0.01）. The mRNA levels of Parkin， Pink1， and P62 in the H/R group were upregulated compared to the control group （P<0.05）， while NGR1 intervention downregulated their expression （P<0.05）. Protein expression levels of Parkin， Pink1， and LC3BⅡ in the H/R group significantly increased， while P62 expression decreased compared to the control group （P<0.01）. In contrast， different doses of NGR1 treatment significantly reduced the expression of Parkin， Pink1， and LC3BⅡ while increasing P62 expression （P<0.05）. TEM revealed that the mitochondrial structure in the H/R group was severely disrupted， with fragmented and disorganized cristae， which was alleviated by NGR1. ConclusionNGR1 ameliorates H/R-induced AC16 cell injury， and its mechanism may be associated with modulating the Pink1/Parkin pathway to suppress excessive mitophagy.

Background Exposure to air pollutants increases the risk of diseases in multiple systems, including respiratory and cardiovascular systems, yet its association with neurological diseases remains unclear. Objective To quantitatively evaluate the association between short-term exposure to air pollutants and outpatient and emergency visits for neurological diseases, identify potential susceptible populations, and quantify associated disease burden. Methods Daily 24-hour average concentrations of fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO), daily maximum 8-hour average concentration of ozone (O₃), daily meteorological data (24-hour average temperature, 24-hour average relative humidity), and data on daily outpatient and emergency department visits for neurological diseases from two hospitals in Conghua District, Guangzhou, China, were collected from 2015 to 2022. A time-stratified case-crossover design was adopted, and a conditional Poisson regression model was constructed to analyze the association between air pollution exposure and neurological disease visits. Two-pollutant models and sensitivity analysis were used to validate model stability. Stratified analyses by season (cold season: from November to March; warm season: from April to October), sex (male, female), and age (≤45 years, 46–60 years, ≥61 years) were performed to identify vulnerable group. Additionally, the number and proportion of neurological disease visits attributable to short-term air pollutant exposure were calculated. Results A total of 72 673 outpatient and emergency department visits for neurological diseases were included during the study period. Most of the patients were middle-aged and elderly individuals (69.89% were over 45 years old) and females (60.25%). The results of single-pollutant models showed that for each interquartile range (IQR) increase in exposure to PM_2.5, PM₁₀, SO₂, NO₂, CO, and O₃, the risk of outpatient and emergency department visits for neurological diseases increased by 7.54% (95%CI: 4.69%, 10.46%), 6.66% (95%CI: 3.92%, 9.46%), 16.72% (95%CI: 10.58%, 23.19%), 8.12% (95%CI: 4.82%, 11.53%), 5.60% (95%CI: 2.34%, 8.97%), and 6.11% (95%CI: 2.91%, 9.40%), respectively. The results of the two-pollutant model showed that the association between PM_2.5 and SO₂ exposure and outpatient and emergency department visits for neurological diseases were relatively stable. The stratified analyses showed that the effect of SO₂ was stronger in the cold season. It was estimated that 8.32% (95%CI: 5.55%, 10.96%) and 6.65% (95%CI: 4.27%, 8.96%) of the outpatient and emergency department visits were attributable to short-term exposure to SO₂ and PM_2.5, respectively. Conclusion Exposure to PM_2.5 and SO₂ is associated with increased risks of outpatient and emergency visits for neurological diseases. SO₂ shows stronger effects during the cold season, and exposure to air pollution contributes to up to 8.32% of neurological disease visits.

OBJECTIVE To study the imaging characteristics of the normal cricoarytenoid joint.METHODS A retrospective study was conducted on the upper airway CT images of 175 subjects with normal laryngoscopic findings.According to age groups,a qualitative evaluation was made of the calcification of the arytenoid cartilage(AC),the hyperplasia of the AC,and the degree of stenosis of the cricoarytenoid joint(CAJ).The study aimed to explore the changing trends of these factors with age.We evaluated the spatial position structures such as the length of the vocal cords(l-VC),the distance between the muscle process of the arytenoid cartilage and the thyroid cartilage(d-MPCC),and the angle of the cricoarytenoid joint(a-CAJ).RESULTS There were differences in calcification of AC,hyperplasia of AC and stenosis of CAJ among different age groups.The calcification of AC(r=0.36,P<0.001),hyperplasia of AC(r=0.49,P<0.001)and stenosis of CAJ(r=0.54,P<0.001)the were positively correlated with age.Bilateral l-VC and a-CAJ were symmetry(all P>0.05).CONCLUSION The morphology of the CAJ was symmetrical in the normal population.It gradually underwent calcification,hyperplasia,and stenosis with age.Upper airway CT examination could evaluate the morphology and spatial position of the CAJ,providing an anatomical reference for clinical practice

Aerosol-assisted plasma amplification laser-induced breakdown spectroscopy(LIBS)was employed for phosphorus detection in water.To address the multivariate coupling effects in LIBS and nebulization sampling system,an orthogonal experiment was employed to systematically optimize the key experimental parameters.Using the orthogonal experimental design,the parametric effects of laser energy(output voltage),signal acquisition delay,liquid velocity,and gas velocity on the signal to background ratio(SBR)of P I 213.618 nm were evaluated,and the optimal conditions were achieved,including laser energy of 86 mJ,delay time of 3 μs,gas velocity of 1.05 mL/min,and liquid velocity of 60 μL/min,which were in agreement with the control-variable optimization results.Moreover,the SBR response trends at P I 213.618 nm with all experimental parameters was strong in consistency with control-variable optimization results,which demonstrated the validity of the orthogonal array experimental design.This study established an efficient and accurate parameter optimization methodology for complex LIBS systems,significantly advancing the application of LIBS in environmental monitoring.

Acute urinary retention(AUR)occurs frequently among astronauts on orbit.The current treatment is complex and easy to damage the urethra,which seriously affects the life and work of astronauts.In contrast,acupuncture,a traditional Chinese remedy,has shown promising results in managing urinary retention.However,the specific acupoints that could potentially prevent AUR remain uncertain due to the unique physiological conditions experienced by individuals in space compared to those on Earth.To address this gap,our research delved into the mechanisms of AUR and acupuncture within both traditional Chinese medicine and modern medical practices.We conducted a thorough literature review from Pubmed,Web of Science,CNKI,Wanfang database,VIP database and Chinese Medical Code database.A hierarchical evidence-scoring approach was utilized to analyze the included literatures,thus devised acupuncture protocols for the treatment of AUR.The outcomes of our study aim to establish a foundation for the application of acupuncture in managing AUR.

Objective To investigate whether transcutaneous electrical acupoint stimulation(TEAS)can improve the muscle strength,endurance and work efficiency of calf muscles in healthy young men,aiming to explore a new method for preventing and combating microgravity-induced muscle atrophy in space environments.Methods 40 healthy young men aged 18-35 years were randomly divided into a Control group(Pseudo Transcutaneous Electrical Acupoint Stimulation)and a Experimental group(Transcutaneous Electrical Acupoint Stimulation)in a 1∶1 ratio,with 20 participants in each group.In the Control group,the indicator light of the stimulator was covered,and the device was turned on,but the electrodes did not contact the skin,The device automatically turned offafter 3 seconds.In the Experimental group,the TEAS device was connected to the current and TEAS intervention was performed.The electrical stimulation waveform was a sperse-dense wave with a frequency of 4/20 Hz,and the intensity was determined by patient tolerance.The acupoints selected for electrical stimulation in both groups were bilateral Zusanli(ST36)、Liangqiu(ST34),Taixi(KI3),and Fuliu(KI7).Zusanli and Liangqiu were paired,and Taixi and Fuliu were paired.The intervention frequency was 30 min/time,1 time/day,6 days/week,for 2 weeks.The relative peak torque at 60°/s,relative peak torque at 180°/s,and average power at 180°/s of the bilateral calf muscles were measured using an isokinetic dynamometer at 0th,7th,and 14d day of the experiment.Results After 1 week of TEAS,compared with Control group,there were no significant changes in the relative peak torque at 60°/s,relative peak torque at 180°/s and average power at 180°/s of the bilateral anterior calf muscles in the Experimental group(all P>0.05);however,compared with Control group,the relative peak torque at 60°/s and the relative peak torque at 180°/s of the bilateral posterior calf muscles in the Experimental group were significantly increased(all P<0.05).After 2 weeks TEAS;compared with the Control group,there were no significant changes in the relative peak torque at 60°/s,relative peak torque at 180°/s and average power at 180°/s of the bilateral anterior calf muscles in the Experimental group(all P>0.05);however,the relative peak torque at 60°/s,relative peak torque at 180°/s,and average power at 180°/s of the bilateral posterior calf muscles were significantly increased in the Experimental group(all P<0.05).Conclusion TEAS of Zusanli,Liangqiu,Fuliu and Taixi acupoints on the lower limbs for 2 weeks can effectively improve the maximum muscle strength,endurance and work efficiency of the posterior calf muscles in healthy young men.

BACKGROUND: Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients. However, the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI) with BP control among hypertension patients is seldom reported, which needs to provide more evidence by prospective intervention studies. We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program. METHODS: Between January 2013 and December 2014, a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China. Workplaces were randomly divided into intervention (n = 40) and control (n = 20) groups. Basic information on employees at each workplace was collected by trained professionals, including sociodemographic characteristics, medical history, family history, lifestyle behaviors, medication status and physical measurements. After baseline, the intervention group received a 2-year intervention to achieve BP control, which included: (1) a workplace wellness program for all employees; (2) a guidelines-oriented hypertension management protocol. HLI including nonsmoking, nondrinking, adequate physical activity, weight within reference range and balanced diet, were coded on a 5-point scale (range: 0-5, with higher score indicating a healthier lifestyle). Antihypertensive medication use was defined as taking drug within the last 2 weeks. Changes in HLI, antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention. RESULTS: Overall, 4655 employees were included (age: 46.3 ± 7.6 years, men: 3547 (82.3%)). After 24 months of the intervention, there was a significant improvement in lifestyle [smoking (OR = 0.65, 95% CI: 0.43-0.99; P = 0.045), drinking (OR = 0.52, 95% CI: 0.40-0.68; P < 0.001), regular exercise (OR = 3.10, 95% CI: 2.53-3.78; P < 0.001), excessive intake of fatty food (OR = 0.17, 95% CI: 0.06-0.52; P = 0.002), restrictive use of salt (OR = 0.26, 95% CI: 0.12-0.56; P = 0.001)]. Compare to employees with a deteriorating lifestyle after the intervention, those with an improved lifestyle had a higher BP control. In the intervention group, compared with employees not using antihypertensive medication, those who consistent used (OR = 2.34; 95% CI: 1.16-4.72; P = 0.017) or changed from not using to using antihypertensive medication (OR = 2.24; 95% CI: 1.08-4.62; P = 0.030) had higher BP control. Compared with those having lower HLI, participants with a same (OR = 1.38; 95% CI: 0.99-1.93; P = 0.056) or high (OR = 1.79; 95% CI: 1.27~2.53; P < 0.001) HLI had higher BP control. Those who used antihypertensive medication and had a high HLI had the highest BP control (OR = 1.88; 95% CI: 1.32-2.67, P < 0.001). Subgroup analysis also showed the consistent effect as the above. CONCLUSION These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.