OBJECTIVE: To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists. METHODS: By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements. RESULTS: The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development. CONCLUSION Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans ; China ; Surveys and Questionnaires ; Genetic Diseases, Inborn/genetics* ; Cross-Sectional Studies ; Genetics, Medical/education* ; Genetic Testing

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Antibody humanization is critical to reduce immunogenicity and enhance efficacy in the preclinical phase of the development of therapeutic antibodies originated from animal models.Computational suggestions have long been desired,but available tools focused on immunogenicity calculation of whole antibody sequences and sequence segments,missing the individual residue sites.This study introduces Site-specific Immunogenicity for Therapeutic Antibody(SITA),a novel computational framework that predicts B-cell immunogenicity score for not only the overall antibody,but also individual residues,based on a comprehensive set of amino acid descriptors characterizing physicochemical and spatial features for antibody structures.A transfer-learning-inspired framework was purposely adopted to overcome the scarcity of Antibody-Antibody structural complexes.On an independent testing dataset derived from 13 Antibody-Antibody structural complexes,SITA successfully predicted the epitope sites for Antibody-Antibody structures with a receiver operating characteristic(ROC)-area unver the ROC curve(AUC)of 0.85 and a precision-recall(PR)-AUC of 0.305 at the residue level.Furthermore,the SITA score can significantly distinguish immunogenicity levels of whole human antibodies,therapeutic antibodies and non-human-derived antibodies.More importantly,analysis of an additional 25 thera-peutic antibodies revealed that over 70％of them were detected with decreased immunogenicity after modification compared to their parent variants.Among these,nearly 66％antibodies successfully iden-tified actual modification sites from the top five sites with the highest SITA scores,suggesting the ability of SITA scores for guide the humanization of antibody.Overall,these findings highlight the potential of SITA in optimizing immunogenicity assessments during the process of therapeutic antibody design.

Objective:To analysis of the latent profiles and influencing factors of body image in patients with postoperative oral cancer.Methods:From July 2024 to March 2025, a total of 332 patients with primary oral cancer confirmed by pathology, aged ≥18 years, and undergoing oral cancer surgery at Hunan Cancer Hospital were selected using simple random sampling and cluster sampling. Among them, 25 were female and 307 were male. The body image scale and the Rosenberg self-esteem scale were used to investigate the patients. The main indicators included the total scale scores and scores on various dimensions of body image, such as appearance evaluation and health focus, with particular attention to satisfaction with facial appearance and oral function.The correlation between self-esteem and body image was analyzed, and differences in scores were compared based on gender, age, self-esteem level, and surgical procedure.Results:Among the 332 patients, 93.4% (310/332) were married, and 6.6% (22/332) were unmarried, divorced, or widowed. A total of 84.3% (280/332) underwent flap transplantation surgery, while 15.7% (52/332) did not. The body image distress in the 332 patients could be categorized into a body image adaptation group [80.12% (266/332)] and a body image disorder group [19.88% (66/332)]. Unmarried/divorced/widowed status ( P=0.020), undergoing flap transplantation ( P=0.006), and self-esteem level ( P<0.001) were identified as influencing factors for postoperative body image disorder in oral cancer patients. Conclusions:Given the varying levels of body image concerns among oral cancer patients, healthcare providers can implement targeted, personalized nursing interventions based on their distinct categories and influencing factors.

BACKGROUND:Competitive athletes exercising in high-temperature,high-humidity,or low-oxygen environments experience intensified skeletal muscle deoxygenation and reduced fat oxidation,which can impair athletic performance.OBJECTIVE:To evaluate the impact of high-temperature,high-humidity,and low-oxygen environments on the fat oxidation rates of athletes during incremental load exercise,and to analyze the differences in deoxyhemoglobin kinetic parameters in skeletal muscle,thereby clarifying the relationship between fat oxidation capacity and skeletal muscle oxygenation under varying environmental conditions.METHODS:Twelve male modern pentathlon athletes were recruited for tests under three environmental conditions:normal(23 ℃,RH45％,FiO2=21.0％),high temperature and high humidity(35 ℃,RH70％,FiO2=21.0％),and low oxygen(23 ℃,RH45％,FiO2=15.6％).Resting metabolism and incremental load exercise were tested.Gas exchange data during and post-exercise were collected to calculate fat oxidation rate,carbohydrate oxidation rate,energy expenditure,and excess post-exercise oxygen consumption.Simultaneous measurements of SmO2 and total hemoglobin in the vastus lateralis muscle were used to calculate deoxyhemoglobin(HHb)levels.Deoxyhemoglobin change parameters-linear fittng slope(ΔEHHb),slope before the inflection point(ΔEHHB-1),and slope after the inflection point(ΔEHHB-2)-were determined using a bilinear function model.Fat oxidation curves were fitted using a SIN function model to identify the intensity(FATmax)that induced maximal fat oxidation(MFO),along with the curve's expansion,symmetry,and translation.RESULTS AND CONCLUSION:(1)Energy metabolism:No significant differences in maximal fat oxidation were observed across environments in each group(P>0.05).Compared with the normal environment group,both high temperature and high humidity group and low oxygen group showed significantly decreased time to maximal fat oxidation and FATmax(P<0.05).The percentage of maximal fat oxidation corresponding to peak oxygen uptake was lower in the low oxygen environment group(P<0.05).Fat oxidation was consistently low in the low oxygen environment group during exercise,while in the high temperature and high humidity environment group,it decreased only at higher exercise loads.Additionally,the expansion parameter was significantly reduced in both high temperature and high humidity and low oxygen environment groups(P<0.05).(2)Deoxyhemoglobin dynamics:The ΔEHHb was significantly higher in the high temperature and high humidity environment group,and ΔEHHB-1 was significantly increased in both high temperature and high humidity and low oxygen environment groups(P<0.05).(3)Correlation analysis:ΔEHHb was significantly negatively correlated with symmetry;ΔEHHB-1 was negatively correlated with FATmax and maximal fat oxidation;ΔEHHB-2 was positively correlated with maximal fat oxidation,and V?O2@BP was positively correlated with symmetry,expansion,and FATmax.(4)These findings indicate that incremental load exercise in high temperature,high humidity,and low oxygen environments accelerates skeletal muscle deoxygenation,thereby inhibiting fat oxidation capacity.Compared with high temperature and high humidity,low oxygen environments may more rapidly disrupt the balance between oxygen delivery and utilization in athletes'skeletal muscle,leading to a greater reliance on anaerobic glycolysis and a consequent reduction in fat oxidation capacity during exercise.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To analysis of the latent profiles and influencing factors of body image in patients with postoperative oral cancer.Methods:From July 2024 to March 2025, a total of 332 patients with primary oral cancer confirmed by pathology, aged ≥18 years, and undergoing oral cancer surgery at Hunan Cancer Hospital were selected using simple random sampling and cluster sampling. Among them, 25 were female and 307 were male. The body image scale and the Rosenberg self-esteem scale were used to investigate the patients. The main indicators included the total scale scores and scores on various dimensions of body image, such as appearance evaluation and health focus, with particular attention to satisfaction with facial appearance and oral function.The correlation between self-esteem and body image was analyzed, and differences in scores were compared based on gender, age, self-esteem level, and surgical procedure.Results:Among the 332 patients, 93.4% (310/332) were married, and 6.6% (22/332) were unmarried, divorced, or widowed. A total of 84.3% (280/332) underwent flap transplantation surgery, while 15.7% (52/332) did not. The body image distress in the 332 patients could be categorized into a body image adaptation group [80.12% (266/332)] and a body image disorder group [19.88% (66/332)]. Unmarried/divorced/widowed status ( P=0.020), undergoing flap transplantation ( P=0.006), and self-esteem level ( P<0.001) were identified as influencing factors for postoperative body image disorder in oral cancer patients. Conclusions:Given the varying levels of body image concerns among oral cancer patients, healthcare providers can implement targeted, personalized nursing interventions based on their distinct categories and influencing factors.

Objective:To investigate the gene expression level of fructose-bisphosphate aldolase A (ALDOA) in non-small cell lung cancer (NSCLC) tissues and the effect of ALDOA on NSCLC prognosis and immune cell infiltration in tumor microenvironment (TME).Methods:The clinical data of patients with lung adenocarcinoma and squamous cell carcinoma, the data of corresponding gene in tumor tissues and corresponding normal lung tissues in The Cancer Genome Atlas (TCGA) database, and the data of healthy population in the Genotype Tissue Expression (GTEx) database were collected in June 2023. Gene Expression Profile Interaction Analysis (GEPIA) 2.0 online tool was used to explore the expression differences of ALDOA at transcription level in NSCLC tissues and normal lung tissues, as well as NSCLC tissues of different stages; the expression of ALDOA was obtained through immunohistochemical staining in different pathological types of NSCLC and normal lung tissues from the Human Protein Atlas (HPA) database; the survival of patients with high and low expression of ALDOA in NSCLC tissues in TCGA database was evaluated by plotting Kaplan-Meier survival curves (differentiated by the median expression of ALDOA at transcription level in NSCLC samples), and log-rank test was used for comparing survival between groups. Using the Tumor Immune Estimation Resource (TIMER) 2.0 database, the CIBERSORT algorithm was applied to evaluate the correlation between ALDOA expression and immune cell infiltration levels in NSCLC tissues from the TCGA database. Further analysis of the correlation between ALDOA expression levels and programmed death receptor ligand 1 (PD-L1), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and various inflammatory factors in NSCLC tissues was conducted using the GEPIA 2.0 online tool to evaluate the impact of ALDOA expression levels on the tumor immune microenvironment.Results:The expression of ALDOA at transcription level in lung adenocarcinoma (483 cases) and lung squamous cell carcinoma (486 cases) tissues were higher than those in corresponding normal lung tissues (347 and 338 cases, respectively), and the differences were statistically significant (all P < 0.01). There was a statistically significant difference in the expression of ALDOA at transcription level among TNM stage Ⅰ, Ⅱ, Ⅲ, and Ⅳ NSCLC tissues ( F = 4.55, P = 0.004), and the expression level of ALDOA gradually increased with the increase of stage. In the HPA database, ALDOA protein stained by immunohistochemistry showed mild to moderate staining in normal lung tissues, while it showed severe staining in lung adenocarcinoma and squamous cell carcinoma tissue samples. Kaplan-Meier survival analysis showed that the overall survival of lung adenocarcinoma patients (239 cases) with high ALDOA expression was worse than that of patients with low ALDOA expression (239 cases) ( P < 0.001), and there was no statistically significant difference in disease-free survival between the two groups ( P = 0.140). There was no statistically significant difference in overall survival and disease-free survival between patients with high expression (241 cases) and low expression (241 cases) of ALDOA in lung squamous cell carcinoma (both P > 0.05). TIMER 2.0 database analysis shows that in lung adenocarcinoma, the expression of ALDOA at transcription level was negatively correlated with the levels of activated mast cells ( Rho = -0.209) and memory B cells ( Rho = -0.133), and positively correlated with the levels of resting mast cells ( Rho = 0.210) and resting natural killer cells ( Rho = 0.110), with statistically significant differences (all P < 0.05). In lung squamous cell carcinoma, the expression of ALDOA at transcription level was negatively correlated with the levels of activated mast cells ( Rho = -0.105), memory B cells ( Rho = -0.213) and CD8 + T cells ( Rho = -0.148), and positively correlated with the levels of resting mast cells ( Rho = 0.173), plasma B cells ( Rho = 0.174) and resting natural killer cells ( Rho = 0.136), with statistically significant differences (all P < 0.05). In NSCLC tissues, the expression of ALDOA at transcription level was negatively correlated with PD-L1 ( R = -0.11), interleukin (IL)-2 ( R = -0.31), IL-4 ( R = -0.14), IL-5 ( R = -0.10), IL-6 ( R = -0.12), and IL-10 ( R = -0.24) levels (all P < 0.001), positively correlated with MMP-9 ( R = 0.11) and VEGF ( R = 0.18) levels (both P < 0.001), and positively correlated with IL-9 ( R = 0.11) and VEGF ( R = 0.18) levels (both P < 0.001), but it was not correlated with IL-17 level ( R = -0.02, P = 0.540). Conclusions:The expression level of ALDOA is elevated in NSCLC tissues, and high ALDOA level in lung adenocarcinoma may indicate poor survival of patients. ALDOA may affect the levels of immune cell infiltration, tumor markers and inflammatory factors in TME, and it may be a potential biomarker for prognosis.

This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals ; Toll-Like Receptor 4/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Rats, Sprague-Dawley ; Rats ; Reperfusion Injury/genetics* ; Male ; Signal Transduction/drug effects* ; Polysaccharides/isolation & purification* ; Polygonatum/chemistry* ; Brain Ischemia/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Humans

Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*