Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels (pLGICs) that mediate rapid cholinergic synaptic transmission throughout the central and peripheral nervous systems. These receptors are integral to neuromuscular junction signaling, autonomic regulation, cognitive learning, reward-related behavior, and neuroplasticity. The nAChR family exhibits remarkable functional diversity through combinatorial assembly of seventeen identified subunits (α1-α10, β1-β4, γ, δ, and ε). Among these, the α9 subunit occupies a distinctive phylogenetic position, exhibiting greater sequence divergence from other neuronal α subunits and possessing unique biochemical properties that distinguish it from all other family members. α9 can form homopentamers and also co-assemble with the α10 subunit to form functional heteropentamers, primarily in (α9)₂(α10)₃ and (α9)₃(α10)₂ stoichiometries. This dual assembly strategy generates functional heterogeneity, as distinct subunit compositions confer differential ion permeation, ligand sensitivity, and desensitization kinetics. The structural determinants governing this stoichiometric variability remain incompletely resolved, representing a critical gap in our mechanistic understanding. Unlike most other nAChR subtypes, traditional agonists of nAChRs (such as nicotine) elicit virtually no agonistic effect on α9* nAChRs (α9-containing receptors, including α9 homopentamers and α9α10 heteropentamers). This pharmacological divergence reflects structural differences within the orthosteric site, particularly in regions at complementary subunit interfaces. As cation-selective channels, α9* nAChRs exhibit high permeability to Ca²⁺. In cochlear outer hair cells, α9α10 nAChRs mediate cholinergic efferent modulation by the medial olivocochlear (MOC) bundle. Acetylcholine-evoked Ca²⁺ influx activates functionally coupled SK2 potassium channels, generating net hyperpolarization that dampens electromechanical amplification through a tightly constrained signaling microdomain. This Ca²⁺-dependent excitatory-to-inhibitory conversion exemplifies sophisticated sensory gain control, and its disruption contributes to noise-induced hearing loss, age-related hearing loss, and tinnitus. Beyond canonical ionotropic signaling, α9* nAChR engages metabotropic transduction pathways. In macrophages, receptor activation modulates cytokine production and inflammatory responses. In keratinocytes, it regulates wound healing by modulating cell migration and differentiation. In dorsal root ganglion sensory neurons, α9* signaling contributes to nociceptive processing and inflammatory hyperalgesia. This functional pleiotropy, spanning both ionotropic signaling and metabotropic transduction, positions α9* nAChR as an exemplary model for investigating signal polymorphism within the pLGIC superfamily. Pathophysiologically, α9* nAChR dysfunction is implicated across multiple organ systems. In the auditory system, disruption of α9α10 nAChR-mediated MOC efferent feedback impairs cochlear gain control, predisposing to noise-induced synaptopathy and age-related hearing loss. In immune cells, dysfunctional α9* nAChR signaling disrupts cholinergic anti-inflammatory pathway activity, exacerbating pro-inflammatory responses. In the peripheral sensory system, aberrant α9* nAChR signaling has been implicated in neuropathic and inflammatory pain states. In skin, impaired receptor function compromises keratinocyte migration and re-epithelialization through disrupted signaling pathways, leading to chronic wound healing defects and inflammation. These pathophysiological associations have catalyzed pharmacological interest, yielding promising chemical entities including α‑conotoxins, small-molecule antagonists/agonists, and allosteric modulators.α-Conotoxin peptides, in particular, demonstrate remarkable subunit selectivity and potent antinociceptive effects in preclinical pain models. However, therapeutic translation faces substantial challenges: the broad tissue distribution of α9* nAChR risks on-target adverse effects in non-target organs; pronounced species differences between rodent and human receptors complicate preclinical validation; and the complexity of ionotropic-metabotropic signaling crosstalk demands pharmacological strategies that extend beyond conventional orthosteric agonism or antagonism. Looking forward, integrating cryo-electron microscopy of full-length receptors in distinct conformational states with single-channel electrophysiology and systems-level circuit analysis promises to illuminate the molecular mechanisms governing α9* nAChR function and regulation. The development of signal pathway-biased ligands and tissue-selective delivery strategies may ultimately harness the therapeutic potential of this receptor while mitigating safety liabilities. As a paradigm for understanding pLGIC signaling diversification, α9* nAChR research will continue to inform broader questions regarding ion channel evolution, allosteric regulation, and pathophysiological mechanisms of chronic pain and autoimmune inflammatory diseases.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Objective:To retrieve and integrate the best evidence on foot offloading management for diabetic high-risk foot patients, and to provide evidence-based basis for effectively preventing the occurrence and development of diabetic foot ulcers.Methods:Clinical practice guidelines, evidence summaries, systematic reviews and expert consensus on the management of foot offloading at high risk of diabetes were searched in Chinese and English databases, domestic and foreign diabetes association websites, clinical decision websites and guideline websites, retrieval time for libraries to March 31, 2024, respectively, by the 2 researchers quality evaluation, evidence extraction, the final summary.Results:A total of 16 articles were included, including 6 guidesline, 5 expert consensuses, 1 evidence summary and 4 systematic reviews. According to the existing evidence, the best evidence of foot offloading management in patients with diabetic high-risk foot was summarized from 6 aspects: evaluation, monitoring, referral, offloading brace, exercise advice and risk factor intervention, 14 subcategories, 32 best evidences for foot offloading management in patients with high-risk diabetic foot.Conclusions:This study summarized the best evidence for foot offloading management in patients with high-risk of diabetic foot, which is convenient for the further development of clinical practice of foot offloading management in patients with high-risk of diabetes, and provides evidence-based basis for clinical medical staff to expand related research.

In the context of"Artificial Intelligence(AI)+Education"era,this study introduces the teaching reform and devel-opment path of the course"Fundamentals of Immunology and Pathogenic Biology"by Professor Lu Fangguo's team at Hunan University of Traditional Chinese Medicine.After twenty years of exploration,the course has successfully transitioned from traditional teaching to intelligent teaching,achieving a comprehensive upgrade in educational concepts,teaching methods,and resources.The reform process is divided into three stages:Early exploration,comprehensive reform,and deepening development.It encompasses the construction of a smart teaching platform,the development and promotion of new forms of digital teaching resources,and the deep integration of ideological and political education.This reform has significantly enhanced teaching quality and students'overall competencies,showcasing the innovative spirit of educators.It has gained nationwide recognition and promotion,providing valuable references for the innovation of medical education in the new era.

This study analyzed soil-transmitted nematode infection surveillance data for children 3-9 years of age in Shaanxi Province from 2016 to 2023,to provide a scientific basis for control strategies for soil-transmitted nematode infections in children in the province.Since 2016,according to the requirements of the National Schistosomiasis and Soil-transmitted Nematode Surveillance Program(Trial),several counties and districts in Shaanxi Province were selected as surveillance sites every year.According to geo-graphical position,the surveillance sites were divided into five areas:east,west,south,north and middle,and one administrative vil-lage(community)was selected in each area for monitoring.The eggs of soil-transmitted nematodes(hookworm,Ascaris lumbricoides,Trichuris trichiura,and Enterobius vermicularis)were detected with the Kato-Katz technique in children 3-9 years of age at each sur-veillance site,and the eggs of Enterobius vermicularis were detected again with the cellophane tape anal swab method.The infection rate and intensity for E.vermicularis were calculated.Detection was performed in 12 462 children 3-9 years old at 75 surveillance sites in Shaanxi Province from 2016 to 2023;84 cases of soil-borne nematode infections were detected,and the overall infection rate was 0.67%.The infection rates for Ascaris lumbricoides and E.vermicularis were 0.18%(22/12 462)and 0.50%(62/12 462),respec-tively,and the infection rates for Trichuris trichiura and hookworm were not found.The infection rates of soil-transmitted nematodes in children were 1.28%(16/1 250),0.16%(2/1 252),1.25%(17/1 365),1.20%(18/1 494),0.17%(2/1 169),1.45%(20/1 382),0.00,and 0.36%(9/251),respectively.A linear trend was observed among years(χ2=11.973,P<0.001).The infection rates in the Weifen Basin ecological region,Loess Plateau ecological region,and Qinba Mountains ecological region were 0.51%,1.19%,and 0.72%,respectively,and the differences were statistically significant(χ2=9.726,P=0.008).Significant differences in infection rates were observed among scattered children(1.63%),preschool children(0.66%),and students(0.57%)(χ2=11.189,P=0.004).No significant differences in infection rates were observed by gender,age,and education level.Compared with the infection rates in the entire country and other provinces,the infection rate of soil-transmitted nematodes among children in Shaanxi Province was low,and the main infection species were Ascaris lumbricoides and E.vermicularis.The infection rates greatly varied within Shaanxi Prov-ince,possibly because of differences in economic development levels,children′s living habits,and personal hygiene status across re-gions.In the future,comprehensive control measures should be taken to strengthen the monitoring and control of key areas,popula-tions,and parasite species.

Objective:To explore the effects of deep hyperthermia on chemotherapy-related adverse effects and immune-inflammatory indicators in the patients undergoing postoperative adjuvant chemotherapy for colorectal cancer.Methods:This retrospective study included 52 patients who underwent surgery for colorectal cancer at the Affiliated Zhongshan Hospital of Dalian University from September 2021 to December 2023. The patients were divided into two groups based on treatment method: the combination group ( n=29) received postoperative adjuvant chemotherapy combined with deep hyperthermia, while the chemotherapy group ( n=23) received postoperative adjuvant chemotherapy alone. Both groups were treated with the XELOX regimen (oxaliplatin + capecitabine). The degree of bone marrow suppression during treatment was assessed by analyzing peripheral blood parameters, including hemoglobin, leukocyte count, neutrophil count, and platelet count. Immune-inflammatory indicators, including complement, procalcitonin (PCT), interleukin-6 (IL-6), systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), were compared before and after treatment in both groups to evaluate the effects of deep hyperthermia on the immune-inflammatory response. Chi-square test or Fisher's exact test (two-tailed) was used to compare bone marrow suppression rates, and the immune-inflammatory indicators between the two groups were compared using t-tests or non-parametric tests, depending on whether the data conformed to a normal distribution. Results:In terms of myelosuppression, the incidence rates of moderate to severe decreases in leukocytes, neutrophils, platelets, and hemoglobin in the combination group were 31%, 31%, 21%, and 14%, respectively, compared to 52%, 61%, 48%, and 9% in the chemotherapy group. The change in PCT levels before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.010). Both the combination group and the chemotherapy group showed significant reductions in SII, NLR and PLR after treatment, and the differences were statistically significant (all P < 0.05). The change in NLR before and after treatment was significantly greater in the combination group than in the chemotherapy group ( P = 0.031). Conclusions:Deep hyperthermia can alleviate chemotherapy-induced adverse effects such as thrombocytopenia and neutropenia in patients undergoing postoperative adjuvant chemotherapy for colorectal cancer. It also appears to improve the inflammatory response in these patients.

OBJECTIVE To understand the development status and existing problems of traditional Chinese medicine(TCM)pharmacists in public TCM hospitals in China,aiming to provide suggestions for the competent departments to formulate management policies for TCM pharmacists and promote the healthy development of TCM.METHODS The data on the number and professional titles of TCM pharmacists in public TCM hospitals in China from 2019 to 2023 were collected.Descriptive analysis was employed to analyze the number,distribution and professional titles of TCM pharmacists in public TCM hospitals across the country,and to measure the quantity shortfalls of the number of TCM pharmacists in these hospitals.RESULTS From 2019 to 2023,the number of TCM pharmacists in public TCM hospitals in China grew slowly,with an average annual growth rate of 2.56%.However,the proportion of TCM pharmacists to the total number of pharmacists in public TCM hospitals gradually decreased,with an average annual growth rate of-0.65%.In terms of hospital grades,the number of TCM pharmacists in tertiary public TCM hospitals showed positive growth,while those in secondary and primary public TCM hospitals showed negative growth.In terms of hospital types,the average annual growth rate of TCM pharmacists in TCM hospitals was 2.22%,in integrated Chinese and Western medicine hospitals it was 7.97%,and in ethnic minority medicine hospitals it was 2.74%.The development of TCM pharmacists in different provinces was uneven.The annual growth rate of TCM pharmacists in Guizhou exceeded 10%,while the growth rate in Hunan and Heilongjiang was negative.In 2023,the number of TCM pharmacists per thousand population in public TCM hospitals was 0.03,indicating a relatively low staffing level.The professional titles of TCM pharmacists in public TCM hospitals were mainly primary and intermediate,with a total of 67.33%.According to the calculation that the proportion of TCM pharmacists to pharmacists was not less than 60%,public TCM hospitals and hospitals of integrated TCM and Western medicine should be reconfigured with TCM pharmacists 6 212 and 1 288 people,respectively.CONCLUSIONS The number of TCM pharmacists in public TCM hospitals is growing slowly,with insufficient staffing levels,relatively low professional titles,and uneven distribution and development across provinces.It is suggested that relevant competent departments strengthen policy guidance,increase the attention given by the state level to TCM pharmacists,strengthen the construction of the talent team for TCM pharmacists,improve the quality and optimize the allocation of TCM pharmacist talents in order to promote the high-quality development of TCM services.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Objective To compare the differences between swept-source optical coherence tomography angiography(SS-OCTA)and ultra-wide-field fluorescein angiography(UWFA)in detecting non-perfusion areas(NPs)in patients with diabetic retinopathy(DR),to evaluate the accuracy of SS-OCTA in predicting NPs outside its visible range,and to explore the distribution patterns of NPs.Methods A retrospective analysis was made on 69 DR patients(88 eyes)who under-went both UWFA and SS-OCTA examinations at the Ophthalmology Department of Sichuan Provincial People's Hospital from December 2022 to September 2024.Manual NP labeling was conducted to compare the detection rate of NPs between the two imaging techniques.The distribution patterns of NPs and the accuracy of SS-OCTA for predicting NPs outside its visible range were also analyzed.Results In a scanning area of 20 mm x 24 mm,the overall NP detection rate by SS-OCTA was 47.40％,with UWFA taken as the standard.The NP detection rate by SS-OCTA was 51.56％in the superotemporal quad-rant,58.35％in the inferotemporal quadrant,45.50％in the superonasal quadrant,and 43.17％in the inferonasal quad-rant.Most NPs occurred in the inferonasal quadrant,accounting for 41.71％of the total NP.The accuracy of SS-OCTA in predicting NPs was 75.00％in the superonasal quadrant and 78.41％in the inferonasal quadrant.The ischemic indices(ISI)of the two imaging techniques were highly positively correlated(r2=0.74).Conclusion Although SS-OCTA can-not yet fully replace UWFA for NP detection in DR patients due to a small visible range,it is still an effective tool to assess retinal ischemia.SS-OCTA has the ability to predict NPs outside its visible range in its scanning range.The inferonasal quadrant is the region where NPs occur most frequently in DR patients,so it is suggested that special attention should be paid to this region in early diagnosis and follow-up periods.

Objective:To explore the efficacy and adverse reactions of CAG regimen combined with venetoclax,chidamide,and azacitidine in the treatment of elderly patients with acute myeloid leukemia(AML).Methods:15 elderly AML patients aged ≥ 60 years old who were admitted to the Hematology Department of our hospital from May 2022 to October 2023 were treated with the CAG regimen combined with venetoclax,chidamide and azacitidine,and the efficacy,treatment-related adverse events,overall survival(OS)and event-free survival(EFS)were analyzed.Results:After one course of treatment,11 out of 15 patients achieved complete response(CR),3 patients achieved CR with incomplete hematologic recovery(CRi),and 1 patient died due to prior infection before efficacy evaluation,and the overall response rate(ORR)was 93.3％(14/15).The median follow-up time was 131(19-275)days,with median OS and EFS both remaining unreached.Next-generation sequencing(NGS)analysis showed that among the 15 patients,13 were detected with gene mutations,and there were 7 genes with mutation frequencies of more than 10％,including ASXL1(4 cases),RUNX1(4 cases),BCOR(3 cases),DNMT3A(3 cases),STAG2(2 cases),IDH1/2(2 cases),and TET(2 cases).Among the 13 patients with detectable mutations,12 patients achieved composite response(CR+CRi).The average recovery time of white blood cell count was 14.6 days after chemotherapy,and the average recovery time of platelets was 7.7 days after chemotherapy.The main adverse event was myelosuppression,with 10 patients accompanied by infection.Except for 1 patient who died due to septic shock during chemotherapy,no patients experienced serious complications such as heart,liver,or kidney damage during the treatment process.Conclusion:The CACAG+V regimen,which combines the CAG regimen with venetoclax,chidamide,and azacitidine,can be applied in the treatment of elderly AML patients,demonstrating good safety and induction remission rate.