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.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Objective: To explore the role of outdoor activity in the relationship between infancy responsive caregiving trajectories and early childhood development, so as to provide a theoretical basis for the promotion of early child development. Methods: The study participants were drawn from the Shanghai Maternal-Child Pairs Cohort and 4 723 mother-child pairs who completed responsive caregiving questionnaires at 2, 6 and 12 months old were included. Questionnaires were used to assess children s responsive caregiving and average daily hours of outdoor activity at 2 years of age. The Age-Stage Questionnaire, Third Edition (ASQ-3) was used to evaluate children s development problems at 2-5 years old. Group based trajectory model was applied to fit infancy responsive caregiving trajectory. Modified Poisson regression was used to analyze associations between different responsive caregiving trajectory groups and child development, and moderating effects were tested for hours of outdoor activity. Results: Infancy responsive caregiving trajectories were categorized into general group ( n =3 871), declining group( n =160), and fluctuating group( n =646). After adjusting for confounding factors, such as parents educational level, annual household income, maternal progestation body mass index,maternal tobacco exposure during pregnancy,maternal anxiety and depression during pregnancy, maternal age at delivery,maternal gestational age,maternal mode of delivery, children s gender,children s birth weight, and duration of breastfeeding, the results of modified Poission regression analysis showed that compared with the general group, children at the age of 2 in declining and fluctuating group had increased risks of suspected developmental delays in communication, gross motor, fine motor, problem solving, and personal-social scales ( OR =1.41,1.31,1.35,1.23,1.21；1.07,1.08,1.08,1.09,1.06);but children only had increased risk of suspected developmental delays in communication of declining group ( OR =1.08), personal-social scales of fluctuating group ( OR =1.06) at 3-5 years of age ( P <0.05). At lower levels of outdoor activity, children in fluctuating group had reduced scores in communication ( β =-1.41), fine motor ( β =-2.34), problem solving ( β =-1.11) and personal-social scales ( β =-1.99) as compared to general group; and children in declining group had reduced scores in gross motor ( β =-4.78)( P <0.05). While at higher levels of outdoor activity, no differences were found between children in fluctuating, declining groups and those in general group in scores of different scales ( P >0.05). Conclusion Prolonged outdoor activity attenuates the adverse effects of declining and fluctuating trajectories of infancy responsive caregiving on early childhood development.

This paper aims to study the effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress(CUMS)-induced depression-like and insomnia behavior models of mice. The CUMS-induced depression-like and insomnia behavior model of mice was established by CUMS treatment for three weeks. The mice were randomly divided into control group, model group, positive drug diazepam group(2 mg·kg~(-1)), as well as low-dose group(1.95 g·kg~(-1)), medium-dose group(3.9 g·kg~(-1)), and high-dose group(7.8 g·kg~(-1)) of Ziziphi Spinosae Semen extracts, with 18 mice in each group. On the 15th day of modeling, the drug was administered intragastrically once a day for one week. Then, the pentobarbital sodium cooperative righting experiment, open field experiment, and elevated plus maze experiment were carried out, respectively. The contents of neurotransmitters 5-hydroxytryptamine(5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) in serum and thalamus of mice, as well as the levels of corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) in serum, were determined by enzyme-linked immunosorbent assay(ELISA). The neuron damage in the hippocampus of mice was observed by hematoxylin-eosin(HE) staining and Nissl staining. Western blot was used to detect the expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), monoamine oxidase A(MAOA), five prime repressors under dual repression binding protein 1(Freud1), synaptic plasticity-related proteins [cellular gene FOS(C-FOS), postsynaptic density protein 95(PSD95), synapsin 1(SYN1), and activity-regulated cytoskeleton-associated gene(ARC)], blood-brain barrier(BBB) permeability-related proteins [zonula occludens 1(ZO-1), occludin, and claudin 1], inflammatory factors [NOD-, LRR-and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), gasdermin D(GSDMD), caspase-3, and caspase-8], and antioxidant factors [nuclear factor erythroid 2-related factor 2(NRF2) and heme oxygenase 1(HO1)] in thalamic tissue of mice. The results indicated that compared with that in the model group, the sleep latency was significantly shortened, and the sleep duration was significantly prolonged in each dose group of Ziziphi Spinosae Semen extracts. The number of visits to the central area of the open field and the distance and time of visits were significantly increased in each dose group of Ziziphi Spinosae Semen extracts. In addition, the proportion of distance and time of entering the open arm area of the elevated plus maze was significantly increased in each dose group of Ziziphi Spinosae Semen extracts. The contents of 5-HT and 5-HIAA in serum and thalamus of mice increased to varying degrees in each dose group of Ziziphi Spinosae Semen extracts; the contents of CRH, ACTH, and CORT in serum of mice were significantly decreased. The protein expression of TPH2 was significantly increased. The protein expression of MAOA, SERT, and Freud1 was significantly decreased. Ziziphi Spinosae Semen extracts could also significantly reduce the protein expression of C-FOS but significantly increase the protein expression of PSD95, ARC, and SYN1. They could reduce the pathological damage of the hippocampus in mice and significantly increase the protein expression of ZO-1, occluding, and claudin 1. The protein expression of NLRP3, GSDMD, ASC, caspase-3, and caspase-8 in the thalamic tissue of mice was significantly decreased, and the protein expression of HO1 and NRF2 was significantly increased. In conclusion, Ziziphi Spinosae Semen extracts could effectively improve sleep disorders and depression-like behaviors in CUMS-induced model mice, which may be related to regulating the 5-HT anabolism process and hypothalamic-pituitary-adrenal(HPA) axis-related hormone levels, reducing pathological damage in the hippocampus, improving synaptic plasticity, repairing BBB integrity, and alleviating inflammatory response and oxidative stress damage.
Animals ; Ziziphus/chemistry* ; Mice ; Male ; Depression/psychology* ; Drugs, Chinese Herbal/administration & dosage* ; Sleep Initiation and Maintenance Disorders/psychology* ; Stress, Psychological/complications* ; Behavior, Animal/drug effects* ; Humans ; Disease Models, Animal

OBJECTIVE: To evaluate the association between erectile dysfunction (ED) and myocardial infarction (MI) using two sample Mendelian randomization. METHODS: A Mendelian randomization study was conducted using comprehensive data on ED and MI from extensive genome-wide association data. Using inverse variance weighted analysis for causal relationships, and correct for confounding factors using multivariate Mendelian randomization, the potential mediating effects were evaluated as well. Based on Genecard data, the genes related to ED and MI were identified. Molecular docking was used to reveal spontaneously bound drug molecules. RESULTS: Our study found that exposure to ED was a risk factor for MI (OR: 1.001 0, 95% CI: 1.000 2－1.001 8, P=0.017 7), which also held true in the validation dataset (OR: 1.028 5, 95% CI: 1.005 0－1.052 6, P=0.017 2). No statistically significant heterogeneity or horizontal pleiotropy was found. The results of reverse Mendelian randomization analysis showed any reverse causal relationship between ED and MI. In multivariate Mendelian randomization analysis, after excluding confounding factors (excluding triglycerides and high-density lipoprotein), the P-value remained less than 0.05, and the OR ranged from 1.000 1 to 1.000 7, indicating that ED was still a risk factor for MI. In the mediation analysis, it was found that the current mediation ratio of smoking to MI was 13.06%. In summary-data-based mendelian randomization analysis, it was found that the gene PTPN11 was a common target gene for MI and ED (OR=0.990, P<0.001). Subsequent molecular docking with sildenafil, clopidogrel, and dapoxetine could spontaneously bind to the PTPN11 gene receptor. CONCLUSION There is a causal relationship between ED and MI, with smoking as a potential mediating factor, and the gene PTPN11 being a co-target gene.
Humans ; Male ; Mendelian Randomization Analysis ; Myocardial Infarction/genetics* ; Erectile Dysfunction/complications* ; Risk Factors ; Genome-Wide Association Study ; Molecular Docking Simulation ; Polymorphism, Single Nucleotide

Objective To investigate the bidirectional causal relationship between different subtypes of endometriosis and female infertility using Mendelian randomization(MR).Methods A two-sample MR analysis was performed on the data sourced from publicly available genome-wide association study(GWAS)of endometriosis and infertility.For each subtype of endometriosis,instrumental variables(IVs)satisfying MR assumptions were selected,with inverse variance weighting(IVW)as primary method.Sensitivity analyses,including Cochran's Q test,MR-Egger regression,and leave-one-out analysis,were conducted to verify the robustness of the results.Statistical significance was set at P<0.01(Bonferroni correction),and P<0.05 was considered as suggestive significance.Results Among different locations of endometriosis,ovary(IVW:OR=1.26,95％CI:1.17～1.35,P<0.001),pelvic peritoneum(IVW:OR=1.26,95％CI:1.20～1.33,P<0.001),rectovaginal septum(IVW:OR=1.11,95％CI:1.06～1.16,P<0.001),adenomyosis(IVW:OR=1.16,95％CI:1.07～1.25,P<0.001),and other types of endometriosis(IVW:OR=1.10,95％CI:1.03～1.17,P=0.004)were significantly associated with infertility.But no such association was observed in fallopian tube and intestinal endometriosis with infertility(P>0.05).Reverse causality analysis indicated that infertility might lead to fallopian tube endometriosis(IVW:OR=1.46,95％CI:1.11～1.93,P=0.007),and was associated with ovarian(IVW:OR=1.56,95％CI:1.27～1.93,P<0.001),pelvic peritoneal(IVW:OR=1.34,95％CI:1.11～1.62,P=0.003),rectovaginal(IVW:OR=1.46,95％CI:1.11～1.93,P=0.007),and other types of endometriosis(IVW:OR=1.61,95％CI:1.21～2.13,P=0.001).Suggestive significance was observed statistically in infertility promoting adenomyosis(IVW:OR=1.16,95％CI:1.07～1.25,P<0.05).It had not been proven yet that infertility could lead to intestinal endometriosis(P>0.05).Sensitivity analyses confirmed the robustness of the results.Conclusion Bidirectional causal relationships exist between different subtypes of endometriosis and infertility.Our findings based on MR analysis validate the clinical observation that endometriosis can lead to infertility,and we exploratively propose an important conclusion that infertility itself may also induce endometriosis.However,due to limited data,the causal relationships between intestinal/tubal endometriosis and infertility require further investigation.

During long-term extravehicular activities(EVA),there have been multiple instances of localized discomfort due to cold extremities such as hands and feet.The primary reason is that the design of space suit gloves prioritizes maximizing operational flexibility,which leads to reduced passive thermal protection in certain areas.Insufficient local thermal protection can cause the hands to lose metabolic heat in cold environments over time,resulting in cold stress.Therefore,it is necessary to conduct research on temperature control technology to meet the thermal comfort requirements of astronauts' hands during EVA.Effective active temperature measures can expand the range of low temperature working environments that astronauts' hands can adapt to during EVA,enhance hand thermal comfort,and ensure hand operational capabilities,preventing excessive cold from exceeding medical requirement and affecting extravehicular missions.This paper combines the metabolic heat generation patterns of the human hand to analyze the temperature control requirements for extravehicular gloves,simulate and optimize the layout of electric heaters,and evaluate the feasibility of the electric heating system for extravehicular gloves by building a thermal simulation model.Through prototype vacuum thermal testing,comprehensive verification of the temperature control module for extravehicular gloves was achieved,demonstrating the effectiveness of the temperature control system.

Objective To analyze the efficacy and safety of unilateral laminectomy and bilateral decompression under unilateral biportal endoscopy(UBE)and microendoscope(MED)in lumbar spinal stenosis.Methods 80 patients with lumbar spinal stenosis from January 2021 to December 2022 were selected and divided into two groups by numerical table method,the control group and the study group,and the number of cases was 40.The grouping method was random number table method.The control group was treated with unilateral laminectomy and bilateral decompression under MED,while the study group was treated with unilateral laminectomy and bilateral decompression under UBE.Operation time,intraoperative blood loss,Oswestry disability index(ODI)and visual analogue scale(VAS)of lumbago and leg pain were obtained before surgery,1,3 months after surgery and at the last follow-up,efficacy and complications were compared between the two groups.Result There were no significant differences in operative time and blood loss between the study group and the control group(P>0.05).1,3 months after surgery and at the last follow-up,ODI in both groups were lower than those before surgery(P<0.05),but there was no difference between the study group and the control group(P>0.05).The VAS of lumbago and leg pain in both groups were lower than those before surgery(P<0.05),at 1,3 months after surgery and the last follow-up,and the study group was significantly lower than the control group(P<0.05).The excellent and good rate of clinical treatment in the study group was 97.50%,and there was no difference compared with 92.50%in the control group(P>0.05).The complication rate of the study group was 2.50%,significantly lower than that of the control group(15.00%)(P<0.05).Conclusion Unilateral laminectomy and bilateral decompression under the UBE and MED have similar efficacy in the treatment of lumbar spinal stenosis,both of which can effectively promote functional recovery,but UBE can reduce pain more effectively and has fewer postoperative complications.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

OBJECTIVE: To compare the effectiveness of robot-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and open freehand TLIF for the treatment of single-level degenerative lumbar spondylolisthesis (DSL) and analyse the influence on postoperative adjacent segmental degeneration (ASD). METHODS: The clinical data of 116 patients with L _4、5 DLS who were admitted between November 2019 and October 2021 and met the selection criteria were retrospectively analyzed. According to the surgical methods, they were divided into the robotic group (45 cases, who underwent robot-assisted MIS-TLIF) and the open group (71 cases, who underwent open freehand TLIF). There was no significant difference in baseline data such as gender, age, body mass index, DLS Meyerding grading, and preoperative Pfirrmann grading, Weishaupt grading, L _{3, 4} intervertebral disc height (DH), L _{3, 4} intervertebral mobility, sagittal parameters [including pelvic incidence (PI), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT)], and Cage height ( P>0.05). The grade of facet joint violation (FJV) by pedicle screws on the superior articular process was assessed postoperatively. Sagittal parameters, L _{3, 4} DH, L _{3, 4} DH loss, and L _{3, 4} intervertebral mobility were measured preoperatively and at last follow-up in order to determine whether ASD occurred. Based on the occurrence of postoperative ASD, logistic regression analysis was used to identify the risk factors for ASD after TLIF. RESULTS: Patients in both groups were followed up 21-47 months, with a mean of 36.1 months; there was no significant difference in the follow-up time between the two groups ( P>0.05). The occurrence of postoperative FJV was significantly better in the robotic group than in the open group ( P<0.05). At last follow-up, the difference in the change values of sagittal parameters PI, PT, SS, and LL was not significant when comparing the two groups of patients ( P>0.05); the change values of L _{3, 4} DH and L _{3, 4} DH loss in the robotic group were smaller than those in the open group, and the change value of L _{3, 4} intervertebral mobility was larger than that in the open group, and the differences were significant ( P<0.05). At last follow-up, ASD occurred in 8 patients (17.8%) in the robotic group and 35 patients (49.3%) in the open group, and the difference in ASD incidence between the two groups was significant ( P<0.05). logistic regression analysis showed that open surgery, preoperative Pfirrmann grading Ⅳ-Ⅴ, preoperative Weishaupt grading ≥2, and postoperative FJV grading ≥1 were risk factors for the development of ASD after TLIF ( P<0.05). CONCLUSION Compared with traditional open surgery, orthopedic robot-assisted MIS-TLIF in the treatment of single-level DLS can more accurately insert pedicle screws, reduce the loss of DH and the occurrence of FJV, and effectively reduce the incidence of mid-postoperative ASD. Preoperative disc and synovial joint degeneration in adjacent segments, nonrobotic-assisted minimally invasive therapy, and FJV are risk factors for ASD after TLIF.
Humans ; Spinal Fusion/methods* ; Spondylolisthesis/surgery* ; Lumbar Vertebrae/surgery* ; Minimally Invasive Surgical Procedures/methods* ; Robotic Surgical Procedures/methods* ; Male ; Treatment Outcome ; Female ; Intervertebral Disc Degeneration/surgery* ; Retrospective Studies ; Postoperative Complications/etiology* ; Risk Factors ; Middle Aged