Objective: To analyze the epidemiological characteristics of category C intestinal infectious diseases among children and adolescents in Shenzhen from 2012 to 2024 and the association with meteorological factors, so as to provide a scientific basis for the targeted prevention and control of infectious diseases for children and adolescents. Methods: Using data from the "Infectious Disease Reporting Information Management System" of the "China Disease Prevention and Control Information System" covering the period from January 1, 2012 to December 31, 2024, the study analyzed clinical and confirmed cases of hand, foot, and mouth disease, other infectious diarrhea, and acute hemorrhagic conjunctivitis among individuals aged 6-19 years old to describe demographic and temporal characteristics. It used Joinpoint regression to calculate the average annual percent change (AAPC) and annual percent change (APC) to analyze incidence trends, and Spearman s correlation was combined to generalize linear models so as to assess the association between category C intestinal infectious diseases and meteorological factors. Results: From 2012 to 2024, a cumulative total of 61 019 cases of hand, foot, and mouth disease among children and adolescents, 58 498 cases of other infectious diarrhea, and 6 377 cases of acute hemorrhagic conjunctivitis were reported. The AAPC in the incidence rates of these three diseases was 19.19%, 31.03% and 31.48 %, respectively(all P <0.05). Notably, the incidence of hand, foot, and mouth disease increased significantly after 2022 (APC= 133.66 %, P <0.01). The temporal distribution showed that hand,foot,and mouth disease was most prevalent in May,June and July (seasonal index of 2.39,3.64,1.97), other infectious diarrhea was most prevalent in February,March and December (seasonal index of 1.22,1.25,1.47), and acute hemorrhagic conjunctivitis peaked in September and October (seasonal index of 4.22,2.16). Monthly average temperature could increase the risk of hand,foot,and mouth disease( β = 0.18 ,95% CI =0.11-0.25); as monthly average wind speed increased, the incidence of other infectious diarrhea ( β =-0.86, 95% CI = -1.50 to -0.22) and acute hemorrhagic conjunctivitis ( β =-1.32, 95% CI =-2.60 to -0.05) both decreased (all P < 0.05 ). Conclusions Among children and adolescents in Shenzhen, category C intestinal infectious diseases remain prevalent throughout the year；the number of reported hand, foot, and mouth disease cases has shown an upward trend in recent years.Temperature and wind speed significantly affect the number of reported cases of three types with category C intestinal infectious diseases.

Objective To analyze Chinese and English publications pertaining to Oncomelania hupensis control from 2005 to 2024, so as to decipher the research status and hotspots of O. hupensis control. Methods Chinese and English publications pertaining to O. hupensis control from 2005 to 2024 were retrieved in the Web of Science Core Collection Database and China National Knowledge Infrastructure. The annual number of publications was analyzed from 2005 to 2024, and the author and institution cooperation networks were mapped using the software CiteSpace 6.3.1. Keywords were extracted from publications to map the co-occurrence, burst and timeline of keywords to identify the research hotspots of O. hupensis control. Results A total of 158 English publications and 771 Chinese publications were included for bibliometric analyses. The overall output of English publications was relatively small from 2005 to 2024, the annual average publication was 7.90 publications. Parasites & Vectors was the most productive journal by the number of publications (21 publications). The three most productive authors included Li Shizhu (24 publications), Zhou Xiaonong (13 publications), and Yang Kun (12 publications), and the three most productive institutions included Chinese Center for Disease Control and Prevention (49 publications), the WHO (27 publications), and Fudan University (25 publications). The annual average number of Chinese publications was high from 2005 to 2015 (57.73 publications), and reduced to 15.11 publications during the period from 2016 to 2024, with Chinese Journal of Schistosomiasis Control as the most productive journal (241 publications). The three most productive authors included Wang Wanxian (18 publications), Sun Qixiang (16 publications), and Dai Jianrong (16 publications), and the three most productive institutions included Jiangsu Institute of Parasitic Diseases (55 publications), Chinese Center for Disease Control and Prevention (47 publications), and Hubei Uni-versity (38 publications). Among the 158 English publications, molluscicidal effect, climate change, geographic information, biological control, machine learning were current research hotspots, and the Yangtze River and elimination were emerging research hotspots. Among the 771 Chinese publications, molluscicidal effect, niclosamide, comprehensive management, molluscicide, effectiveness evaluation, marshland, and endophyte were current research hotspots, and the future research hotspots shifted to molluscicidal effect and pyriclobenzuron. Conclusions Limited attention is paid to the research on O. hupensis control across the world. The Yangtze River, elimination, molluscicidal effect, and pyriclobenzuron may be future research hotspots. High attention is recommended to be paid to the research on O. hupensis control, and development of diverse approaches for O. hupensis control is of urgent needs. We should continue to attach importance to the control research of O. hupensis and strengthen the exploration of diverse snail extermination and control methods.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Objective To explore the effects of drug-coated balloons(DCB)on the patency rate of target lesion vessels,coagulation function and vascular endothelial function in patients with in-stent restenosis(ISR)after percutaneous endovascular angioplasty(PTA)for lower extremity arteriosclerosis obliterans(ASO).Methods A total of 62 patients with ISR and ASO admitted to the hospital were retrospectively enrolled between March 2020 and March 2022.According to different treatment methods,they were divided into DCB group(n=38)and common balloon(SAB)group(n=24).All were followed up for 12 months after surgery.The changes in primary patency rate of target lesion vessel,clinically driven-target lesion revascularization(CD-TLR)rate,late loss of values in the lumen(LLL),ankle-brachial index(ABI),coagulation function indexes[prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),D-dimer(D-D)]and vascular endothelial function indexes[serum endothelin-1(ET-1),nitric oxide(NO),flow-mediated dilatation(FMD)]were observed,and the occurrence of postoperative complications in the two groups was recorded.Results At 12 months after surgery,primary patency rate of target lesion vessels in DCB group was higher than that in SAB group(86.84％vs 50.00％),CD-TLR rate,LLL and ABI were lower than those in SAB group[13.16％,(1.39±0.52)mm,(0.76±0.12)vs 50.00％,(1.79±0.64)mm,(0.62±0.11);P＜0.05].At24h and 2 weeks after surgery,there was no significant difference in PT,APTT,FIB or D-D between the two groups(P＞0.05).At 24h and 2 weeks after surgery,levels of serum ET-1 in DCB group were lower than those in SAB group[(66.65±7.12)pg/ml,(65.58±6.98)pg/ml vs(71.74±6.92)pg/ml,(68.84±6.51)pg/ml)],while NO levels were higher than those in SAB group[(32.21±4.17)pg/ml,(34.62±3.32)pg/ml vs(28.53±5.23)pg/ml,(31.21±4.19)pg/ml;P＜0.05].At 2 weeks after surgery,FMD in DCB group was higher than that in SAB group[(12.49±5.33)％vs(9.14±4.42)％,P＜0.05].There was no significant difference in the total incidence of complications between the two groups(21.50％vs 12.50％,P＞0.05).Conclusion Compared with SAB,DCB can effectively protect vascular endothelial function and improve the primary patency rate of ISR after PTA in patients with lower extremity ASO.

This study investigated the infection status,drug resistance,and molecular characteristics of Shiga toxin-producing Escherichia coli(STEC)in domestic goats in Chengkou county,Chongqing.In August 2023,283 fecal samples were collected from households in Chengkou county.After enrichment with EC broth and inoculation onto selective media,samples that tested positive for stx1/stx2 were selected for further isolation.The positive strains were investigated with antimicrobial susceptibility testing and whole genome sequencing.According to the whole genomic sequences,the stx subtypes,serotypes,multi-locus sequence types,virulence genes,drug resistance genes,and phylogenetic relationships of the STEC strains were analyzed.Forty-six strains of STEC were isolated from 283 goat fecal samples,thus resulting in a detection rate of 16.25%.The 46 STEC strains were categorized into 12 O∶H serotypes,among which O76∶H19 and O8∶H7 predominated,each represented by 9 strains.Five STEC strains were identified as serotype O157∶H7.The 46 STEC strains were categorized into 11 sequence types(STs),among which ST675 and ST196 predominated,each represented by nine strains,accounting for a 19.57%proportion.The strains were categorized into 7 stx subtypes,among which stx1c(26/46,56.52%),followed by stx2k(9/46,19.57%)predominated.All nine Stx2k-STEC strains were identified as serotype O8∶H7 and sequence type ST196.In antimicrobial susceptibility testing,2 STEC strains were resistant to ampicillin,one strain was resistant to ampicillin/sulbactam,one strain was resistant to cefazolin,and one strain was resistant to cefoxitin.Nine Stx2k-STEC strains were found to carry the beta-lactam resistance gene blaEC-18.Antimicrobial sensitivity tests revealed that the nine Stx2k-STEC strains were sensitive to all 15 tested antibiotics.Moreover,phylogenetic analysis indicated that the 9 Stx2k-STEC strains were remarkably similar but showed high genetic diversity with respect to that of the Stx2k-STEC strains isolated from other regions in China.Goatsare an important animal reservoir for STEC in theChengkou district of Chongqing,and novel sequence type Stx2k-STEC strains distinct from those found in other regions of China were identified in this region.

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Due to its high sensitivity and non-destructive nature, Raman spectroscopy has become an essential analytical tool in biopharmaceutical analysis and drug development. Despite of the computational demands, data requirements, or ethical considerations, artificial intelligence (AI) and particularly deep learning algorithms has further advanced Raman spectroscopy by enhancing data processing, feature extraction, and model optimization, which not only improves the accuracy and efficiency of Raman spectroscopy detection, but also greatly expands its range of application. AI-guided Raman spectroscopy has numerous applications in biomedicine, including characterizing drug structures, analyzing drug forms, controlling drug quality, identifying components, and studying drug-biomolecule interactions. AI-guided Raman spectroscopy has also revolutionized biomedical research and clinical diagnostics, particularly in disease early diagnosis and treatment optimization. Therefore, AI methods are crucial to advancing Raman spectroscopy in biopharmaceutical research and clinical diagnostics, offering new perspectives and tools for disease treatment and pharmaceutical process control. In summary, integrating AI and Raman spectroscopy in biomedicine has significantly improved analytical capabilities, offering innovative approaches for research and clinical applications.

OBJECTIVE: To explore the feasibility and effectiveness of repairing surgical defect in pharyngo-laryngeal malignant tumor with free rectus femoris flap. METHODS: The clinical data of 34 patients with surgical defects in pharyngo-laryngeal malignant tumor who met the selection criteria between July 2014 and August 2024 were retrospectively analyzed. There were 25 males and 9 females, aged 25-82 years, with a median age of 54 years. The disease duration ranged from 2 months to 2 years, with a median of 7 months. The tumor locations included the oropharynx, hypopharynx, cervical esophagus, and larynx. Pathological types included squamous cell carcinoma (29 cases), myoepithelial carcinoma (2 cases), adenoid cystic carcinoma (1 case), and diffuse large B-cell lymphoma (2 cases). TNM staging: 16 cases of T ₄N ₁M ₀, 3 cases of T ₄N ₂M ₀, 3 cases of T ₄N ₀M ₀, 10 cases of T ₃N ₁M ₀, and 2 cases of T ₃N ₀M ₀. The 2017 American Joint Committee on Cancer (AJCC) staging was stage Ⅲ in 2 cases and stage Ⅳ in 32 cases. The blood supply of the proximal rectus femoris muscle was observed by enhanced CT of the lower limb vessels before operation, and the surgical defects ranged from 3.0 cm×2.0 cm to 12.0 cm×8.5 cm. The blood supply and perforators of rectus femoris muscle were explored during operation, and the free rectus femoris flap pedicled with the direct vascular stem of rectus femoris muscle was used to repair the defect. For the patients with pharyngeal fistula or obvious neck swelling after operation, the blood supply of the flap was analyzed by vascular enhanced CT to determine the corresponding strategies of nutritional support, anti-infection, dressing change and drainage. Radiotherapy and chemotherapy were supplemented in 27 patients with lymph node metastasis after operation. RESULTS: All the 34 patients were followed up 1-10 years, with an average of 3 years. The flap was found to be necrotic by fibrolaryngoscopy at 1 week after operation in 2 cases, and the incision healed after dressing change and nutritional support, and no reoperation was performed. The flap was in good condition at 1 week after operation in 4 cases, and the signs of gradual necrosis of the flap were found within 1 month after operation, of which 2 cases were healed after dressing change, 1 case was removed the necrotic tissue by reoperation, and 1 case was healed after pectoralis major myocutaneous flap was used to repair the pharyngeal tissue defect. The flaps survived in 28 cases, including 4 cases of pharyngeal fistula, which healed by dressing change. Twenty-two cases achieved satisfactory results in swallowing or phonation. Two patients with total laryngectomy and voice reconstruction underwent reoperation to seal the voice tube because of postoperative aspiration. During the follow-up, 1 case had tracheal stomal recurrence, 2 cases had bone metastasis, and 1 case had bone and lung metastasis. CONCLUSION The free rectus femoris flap has good flexibility, the volume of the flap is easy to adjust, and the incision of the donor site is concealed, which is expected to become a new choice for the repair of the surgical defect in pharyngo-laryngeal malignant tumor.
Humans ; Male ; Middle Aged ; Female ; Aged ; Adult ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Laryngeal Neoplasms/pathology* ; Aged, 80 and over ; Pharyngeal Neoplasms/pathology* ; Free Tissue Flaps/blood supply* ; Quadriceps Muscle/transplantation* ; Surgical Wound/surgery* ; Treatment Outcome