ObjectiveTo explore the role of cuproptosis and identify cuproptosis-related genes in Wilson disease （WD） through bioinformatics analysis and clinical validation，providing implications and directions for the diagnosis and treatment of WD. Methods（1） Screening of target genes： The differentially expressed genes （DEGs） between WD and healthy control were obtained from GeneCards，and the cuproptosis-related genes were obtained from Gene Expression Omnibus （GEO） and published literature.The cuproptosis-related genes in WD were obtained by intersection.Through gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses，the specific biological process，functions or metabolic pathways of cuproptosis-related genes in WD were predicted.Molecular docking and PyMOL visualization were then performed to analyze and verify the potential regulatory mechanism of Gandou Fumu Decoction for cuproptosis.（2）Validation of target genes： The blood samples of 15 WD patients treated in the department of encephalopathy and 15 healthy volunteers undergoing physical examinations in the health management center were randomly collected from the First Affiliated Hospital of Anhui University of Chinese Medicine.The expression levels of target genes were determined by Western blot and real-time PCR. Results（1） A total of 3 607 DEGs in WD were obtained from GSE107323 in GEO，and 68 cuproptosis-related genes were obtained from GeneCards and published literature.Twelve common target genes were obtained by intersection，including three up-related genes（SQSTM1，MIF1，and TAX1BP1） and nine down-regulated genes（CP，SERPINE1，AOC3，GPX4，SLC27A5，VEGF-A，PDHB，PDK1，and ATP7B）.The common target genes were mainly enriched in monocarboxylic acid metabolism，oxidoreductase activity，negative regulation of molecular functions，which mainly involved HIF-1，ferroptosis and other signaling pathways.Molecular docking and PyMOL visualization results showed Gandou Fumu Decoction had good binding ability with the cuproptosis-related genes PDK1，SERPINE1，VEGFA，and AOC3 in WD.（2）A total of 30 blood samples were collected，including 15 WD patients and 15 health volunteers.Western blot results showed that expression levels of target genes were consistent with the results obtained by bioinformatics analysis.RT-qPCR results showed that compared with healthy volunteers，WD patients had down-regulated mRNA levels of SERPINE1，GPX4，SLC27A5，and VEGF-A and up-regulated mRNA levels of SQSTM1 and MIF1（P<0.05）. ConclusionThe expression levels of cuproptosis-related genes in WD patients are consistent with the results predicted by bioinformatics analysis.The characteristic preparation Gandou Fumu Decoction of Xin'an Medicine showed good binding abilities with the cuproptosis-related genes in WD.Cuproptosis may play a key role in the pathophysiological mechanism of WD，which can provide a new target for the diagnosis and treatment of WD.

Objective To enhance the standardization of surgical operations,shorten the learning curve,and reduce surgical complications by summarizing common errors and proposing solutions for beginners during pre-study of cavity construction in non-inflatable axillary approach laparoscopic thyroid surgery.Methods A retrospective analysis was made on 210 patients who underwent noninflatable axillary approach luminal thyroid surgery at the Department of Head and Neck Surgery,Zhejiang Provincial People's Hospital,between January 2022 and June 2023.Among them,150 patients were luminalized by the practitioners in the practice group,while 60 patients were luminalized by the practitioners in the skilled group.The occurrence of nine common errors during cavity construction,such as supraclavicular nerve injury and scapulohumeral muscle injury,was assessed and compared between the two groups.Results There was no statistically significant difference in age,gender,tumor diameter,tumor location or pathology type between the two groups(P＞0.05).The staff in the practice group had a significant difference in supraclavicular cutaneous nerve injury(19.33％vs.3.33％),scapulohumeral muscle injury or disarticulation(16.00％vs.0),anterior cervical band of free excess(24.00％vs.3.33％),pectoralis major muscle and supraclavicular fascia injury(16.00％vs.5.00％),external jugular vein and genuine branch injury(8.00％vs.0),excessive freeing of the sternoclavicular joint(7.33％vs.0),and incorrect entry of the sternocleidomastoid muscle gap(8.67％vs.0)were significantly higher in incidence than the employees in the skilled group(P＜0.05).There was no statistically significant difference between employees in the practice group and those in the skilled group in terms of injury to the internal jugular vein and its geniculate branches(4.00％vs.0),and incorrect entry of the anterior cervical strap muscles into the hierarchy(2.00％vs.0)(P＞0.05).Conclusion The incidence of damage to the surrounding tissue was significantly higher in the novice group than in the expert group during endoscopic thyroid surgery for space construction.A solid anatomical foundation and proficient endoscopic surgical technique serve as fundamental prerequisites for achieving a successful space system construction.By summarizing common challenges and providing corresponding solutions encountered during endoscopic thyroid surgery,this study further enhances and refines the learning system for total endoscopic thyroid procedures.

BACKGROUND:The recovery of function after spinal cord injury depends on the functional remodeling of the motor cortex.However,the anatomical evidence underlying the functional remodeling of the motor cortex is still illusive.Analyzing the anatomical changes in the motor cortex after spinal cord injury can provide new ideas and research directions for regulating functional recovery and rehabilitation after spinal cord injury. OBJECTIVE:To analyze the neural circuit structural basis of functional remodeling of the primary motor cortex after spinal cord injury. METHODS:C57BL/6J mice were randomly divided into a sham operation group and a spinal cord injury group.The adeno-associated virus vectors expressing the fusion protein of Cre recombinase were injected into C4 of mice of both groups.The adeno-associated virus vectors with Cre recombinase-inducible expression of avian sarcoma/leukosis envelope glycoprotein receptor TVA and rabies glycoprotein were injected into the primary motor cortex.Fourteen days later,a C6 dorsal hemisection mice model was established in the spinal cord injury group.The pseudotyped rabies virus was injected into the primary motor cortex of mice of both groups.After 7 days,brain samples were collected and frozen sections were made.The distribution of input neurons innervating corticospinal motor neurons in the brain was observed and analyzed quantitatively. RESULTS AND CONCLUSION:Fluorescence microscopy observation and quantitative analysis found that input neurons innervating corticospinal motor neurons of the primary motor cortex in mice of both groups were distributed in the cerebral cortex,thalamus and midbrain.Among them,in the sham operation group,the number of input neurons in the mouse cerebral cortex accounted for(84.0±3.6)%of total brain input neurons;that in the thalamus accounted for(10.6±2.3)%,and that in the midbrain accounted for(0.7±0.4)%.Direct synaptic input neurons in the spinal cord injury group accounted for(81.7±1.0)%,(13.1±0.5)%,and(1.6±0.8)%in the cerebral cortex,thalamus and midbrain,respectively.The proportion and number of primary motor cortex input neurons in the three regions of the spinal cord injury group did not differ significantly from that of the sham operation group.After spinal cord injury,the number of input neurons innervating corticospinal pyramidal motor neurons in various brain regions did not change significantly,suggesting that functional remodeling of the motor cortex after spinal cord injury may not only depend on changes in synaptic input related to injured corticospinal motor neurons,but also on transcriptional regulation changes within the injured neurons themselves.

AIM: To study the perception of first-order grating acuity and second-order spatial contrast sensitivity in patients with monocular anisometropia amblyopia.METHODS:A total of 715 children(715 eyes)diagnosed as monocular anisometropia amblyopia in our hospital from January 2018 to December 2022 were collected as amblyopia group, and 745 children(745 eyes)with normal corrected visual acuity were collected. The best corrected visual acuity(BCVA), first-order grating acuity and/or second-order spatial contrast sensitivity were measured, repectively. The perception ability of amblyopia patients to first-order grating acuity and second-order spatial contrast sensitivity were analyzed.RESULTS:There were significant differences between amblyopia group and normal control group in the perception of first-order grating acuity(11.58±6.10 vs. 20.27±3.47, P<0.001)and second-order spatial contrast sensitivity(0.33±0.16 vs 0.12±0.04, P<0.001). And there were significant differences between mild-to-moderate amblyopia and severe amblyopia patients in first-order grating acuity(12.10±6.23 vs. 8.13±3.70, P<0.001)and second-order spatial contrast sensitivity(0.32±0.16 vs. 0.37±0.17, P<0.05).CONCLUSION: The first-order and second-order visual pathway of the cerebral cortex in children with monocular anisometropia amblyopia have different degrees of damage. The injury of severe amblyopia is more serious than that of mild-to-moderate amblyopia.

ObjectiveTo analyze the characteristics of HIV-1 molecular network and pretreatment drug resistance genes in the middle-aged and elderly people aged ≥50 years in Huzhou City, Zhejiang Province, and to provide an evidence for the prevention and control of AIDS epidemic. MethodsA total of 332 samples from the newly reported and untreated AIDS patients aged ≥50 years in Huzhou City from January 2020 to December 2023 were collected, pol genes were amplified by reverse transcription polymerase chain reaction (RT-PCR) and nested polymerase chain reaction (nest⁃PCR). Phylogenetic trees analyzing the subtypes were constructed, and a molecular network with a gene distance threshold of 1.0% were constructed at the same time. Mutation sites of drug resistance-related genes were identified through the Data Analysis and Detection System of HIV-1 Resistance Gene Detection of Stanford University, USA. ResultsSequence samples of 308 patients were obtained, and9 genotypes were identified, including CRF07_BC in 172 cases (55.8%), CRF01_AE in 61 cases (19.8%), CRF08_BC in 43 cases (14.0%), CRF85_BC in 9 cases (2.9%), and CRF55_01B in 8 cases (2.6%), subtype B in 5 cases (1.6%), subtype C in 4 cases (1.3%), CRF67_01B in3 cases (1.0%), and unique recombination URF01_AE/07_BC in 3 cases (1.0%). When the gene distance threshold was 1.0%, 28 molecular clusters were formed, and 139 cases were connected to the network, with an access rate of 45.0%. The largest transmission cluster C1 contained 44 cases infected with CRF07_BC subtype, all of whom were heterosexually transmitted, and predominantly by males. A total of 30 patients were found to have low-grade or higher drug resistance mutations, and the pretreatment drug resistance rate was 9.7% (30/308). Among them, there were 5 cases (16.7%) of protease inhibitor (PI) related drug resistance mutations, and 26 cases (86.7%) of non-nucleoside reverse transcriptase inhibitors (NNRTI) related drug resistance mutations. ConclusionCRF07_BC is the subtype with the most clusters among the middle-aged and elderly infected patients aged ≥50 years in Huzhou City. Middle-aged and elderly transmission clusters are formed within the three counties of WX, NX and CX through related activities. Molecular network monitoring on newly reported cases aged ≥50 years in Huzhou City should be strengthened so that the new characteristics of epidemic changes can be detected in time, providing a scientific basis for adjusting AIDS prevention and control measures for the elderly.

Objective:To analysis the necessity of additional surgical intervention for non-curative endoscopic resection patients with early gastric cancer.Methods:A retrospective analysis was conducted on 73 patients with early gastric cancer who underwent additional surgical procedures after non-curative endoscopic resection at Chinese PLA General Hospital from July 2009 to May 2023. The main outcome measures included pathological classification, positive horizontal margins, positive vertical margins, invasion depth, vascular and lymphatic invasion, eCura grade, lymph node metastasis, and overall survival rate.Results:A total of 73 patients with early gastric cancer who were determined to have non-curative endoscopic resection underwent additional surgical procedures, including 58 males and 15 females with a mean age of 61 (53-67) years. In terms of the site of onset, 37 cases were located in the upper part of the stomach, 24 cases in the lower part, 11 cases in the middle part, and 1 case had multiple lesions. In terms of pathological classification, 43 cases were highly differentiated tubular adenocarcinoma, 16 cases were mucinous/signet ring cell carcinoma, 10 cases were poorly differentiated tubular adenocarcinoma, and 4 cases were high-grade intraepithelial neoplasia. In terms of morphological classification, 22 cases were type 0-Ⅱa, 43 cases were type 0-Ⅱb, and 8 cases were type 0-Ⅲ. In terms of invasion depth, 17 cases were mucosal cancer, 23 cases had submucosal invasion less than 500 μm, and 33 cases had submucosal invasion more than 500 μm. In terms of vascular and lymphatic invasion, 8 cases had lymphatic vessel invasion and 8 cases had venous invasion. Among the 73 patients, 4 were diagnosed as having eCura A, 5 as eCuraB, 4 as eCura C1, and 60 as eCura C2. Among the 60 patients diagnosed as having eCura C2, only 2 cases (3.3%) were found to have lymph node metastasis around the stomach based on postoperative pathological evaluation. Among the 73 endoscopic specimens, 7 patients had positive horizontal margins, 21 had positive vertical margins, and 2 had positive margins in both directions, totaling 30 patients with positive horizontal or vertical margins. According to postoperative pathological evaluation, 9 cases (30.0%) had residual tumors in the original site. Among the 73 patients, 5 were lost to follow-up and 4 died, resulting in an overall survival rate of 94.12% (64/68) and disease-specific survival rate of 98.53% (67/68). The follow-up time of patients was 61.37 (10-166) months.Conclusion:For early gastric cancer patients with eCura C2 following non-curative endoscopic resection, additional surgery is feasible. However, the proportion of patients with actual lymph node metastasis is relatively low.

ObjectiveTo analyze the epidemiological characteristics and etiology of clustered outbreaks of hand， foot， and mouth disease （HFMD） in Pudong New Area， Shanghai from 2017 to 2022， and to provide a scientific basis for the prevention and control of HFMD in the area. MethodsThe data related to HFMD clustered outbreaks from 2017 to 2022 were obtained from the Pudong New Area HFMD outbreak database. Descriptive analysis was conducted to explore the outbreak scope， seasonal characteristics， distribution of occurrence settings， and etiological composition. ResultsFrom 2017 to 2022， Pudong New Area reported a total of 2 547 HFMD clusters， involving 8 884 cases， with an average of 3.49 cases per event. The majority of events （78.52%） had between 2 and 4 cases. The peak reporting periods for clustered HFMD from 2017 to 2019 and in 2021 were during the summer （May‒July） and autumn （September‒November）. The seasonal pattern was less distinct in 2020 and 2022， likely due to the impact of the COVID-19 pandemic. The majority of clustered outbreaks occurred in childcare facilities （44.64%）， followed by households/neighborhood committees （44.21%）， with schools accounting for a smaller proportion （12.39%）. The etiology revealed the coexistence of multiple enterovirus genotypes， with a positive detection rate of 60.46%， and CoxA6 being the dominant strain. ConclusionHFMD clustered outbreaks in Pudong New Area show fluctuating trends， with significant yearly differences in the number of incidents. The predominant seasons for outbreaks are summer and autumn， with CoxA6 identified as the dominant strain. The implementation of prevention and control measures for COVID-19 significantly reduced the occurrence of HFMD outbreaks. Continuous monitoring and focus on large-scale clustered outbreaks in key institutions are essential for the future.

Objective: To investigate the characteristics of HIV-1 molecular transmission network among HIV/AIDS patients in Zhoushan City, Zhejing Province. Methods: The newly reported HIV/AIDS cases in Zhoushan City from 2020 to 2022 were selected. Basic information was collected and whole blood samples were obtained at the initial follow-up. The pol gene sequences of HIV-1 were amplified by RT-PCR and nested-PCR. HIV-1 subtypes were identified by Neighbor-Joining phylogenetic trees. The HIV-1 molecular transmission network was built and analyzed using Cytoscape 3.6.1 software. Results: A total of 222 HIV/AIDS cases were reported in Zhoushan City from 2020 to 2022, 200 whole blood samples were collected, and 152 sequences were obtained successfully, including 122 males (80.26%), 75 cases aged 50 years and above (49.34%), 109 cases with a junior high school education or below (71.71%), and 63 cases with commercial heterosexual contact (41.45%). The main subtypes were CRF07_BC and CRF01_AE, accounting for 45.39% and 21.05%, respectively. When the threshold of genetic distance was set to 1%, 20 molecular clusters were formed in 69 cases, with a clustering rate of 45.39%. Using the molecular network constituted by reported HIV/AIDS cases in 2020 as the baseline network, there were 2 active molecular clusters with ≥5 new cases in 2022, each with 9 cases, characterized mainly by individuals aged 50 or above, with a junior high school education or below, and transmission through commercial heterosexual sex. Conclusions The predominant HIV-1 subtypes among HIV/AIDS cases in Zhoushan City are CRF07_BC and CRF01_AE. Transmission through commercial heterosexual contact among middle-aged and elderly people is a main mode of HIV transmission.

Objective:To explore the mediation effects of perceived social support and work-family conflict on clinical nurses′ self-efficacy and parenting stress, and to provide theoretical basis for formulating intervention programs for parenting stress.Methods:A total of 631 clinical nurses from 8 grade A hospitals in Anhui Province were selected by convenience sampling method from August to October 2023. A cross-sectional survey was conducted with the general data questionnaire, the Chinese version of Work-Family Behavioral Role Conflict Scale, the Parenting Stress Scale for Clinical Nurses, the Perceptived Social Support Evaluation Scale and the General Self Efficacy Scale to analyze the relationship between perceptive social support, work-family conflict, self-efficacy and parenting stress and the mediating effect.Results:A total of 603 clinical nurses were included, including 9 males and 594 females, aged (35.16 ± 4.59) years. The total scores of work-family conflict, parenting stress, understanding of social support and self-efficacy were (87.10 ± 14.38), (51.00 ± 9.51), (59.91 ± 11.57) and (26.68 ± 6.27) points. The total effect of self-efficacy on parenting stress was - 0.385. The mediating paths of self-efficacy on parenting stress included: self-efficacy→perceived social support→parenting stress; self-efficacy→work-family conflict→parenting stress; self-efficacy→perceived social support→work-family conflict→parenting stress. The three indirect effects accounted for 18.69%, 53.72% and 16.87% of the total effect.Conclusions:Social support and work-family conflict have a chain mediation effect between clinical nurses′self-efficacy and parenting stress. Nursing managers can improve the self-efficacy of clinical nurses and enhance the understanding of social support to help reduce work-family conflict, so as to effectively alleviate the level of child-rearing stress of clinical nurses.

Objective:To investigate the effectiveness, safety, and advantages of modified radical neck dissection by gasless unilateral axillary approach (GUA-MRND) in the surgical management of selected patients with papillary thyroid cancer.Methods:We retrospectively analyzed patients with papillary thyroid cancer who underwent GUA-MRND (endoscopic group, n=16) versus unilateral open modified radical neck dissection (MRND) (open group, n=32) during the period from Jan. 2019 to Jun. 2021, including the differences in surgical efficiency, complication rate, and incisional satisfaction.Results:Compared MRND with GUA-MRND, the patients were younger ( P<0.05) , operative time and postoperative drainage anterior ( P<0.01) were slightly inferior in the latter, but it had obvious advantages in cervical swallowing discomfort and incision satisfaction evaluation ( P<0.05) . There was no significant difference in the incidence of temporary recurrent laryngeal nerve injury, intraoperative and postoperative bleeding, hematoma, infection, lymphatic or chylous leakage and supraclavicular numbness after surgery ( P>0.05) . The number of dissected lymph nodes in area II in the GUA-MRND was lower ( P<0.05) , but it was significantly higher ( P<0.01) in area III. And the average regional cleaning efficiency in the GUA-MRND was level Ⅲ (35.5%) , level Ⅵ (28.59%) , level Ⅳ (23.21%) , level Ⅱ (7.18%) and level Ⅴ (7.12%) , suggested that GUA-MRND had higher efficacy for level III, level Ⅵ and Level IV. Conclusion:GUA-MRND is safe, effective, and has high cosmetic satisfaction in the treatment of selected patients with lateral cervical lymph node metastases from papillary thyroid cancer.