ObjectiveThis paper aims to investigate the distribution patterns of traditional Chinese medicine syndromes in patients with chronic hepatitis B （CHB） comorbid with metabolically associated fatty liver disease （MAFLD） and analyze their correlation with clinical characteristics and the progression of liver fibrosis. MethodsA cross-sectional study method was employed， and 506 patients with CHB comorbid with MAFLD who attended the Hepatology Outpatient Department of Public Health Clinical Center of Chengdu from June 2024 to December 2024 were enrolled. General information， traditional Chinese medicine syndromes information， laboratory indicators， and imaging examination results were collected using case report forms （CRF）. Tongue images of patients were acquired using a tongue diagnosis instrument， and tongue feature parameters were extracted using computer image processing technology. Frequency analysis， factor analysis， and cluster analysis， and other methods were used to explore syndrome categories and distribution patterns. Non-parametric tests were used to compare the differences in clinical characteristics among different syndromes. Univariate and multivariate logistic regression analyses were performed to investigate the correlation between traditional Chinese medicine syndromes and the progression of liver fibrosis. ResultsThe main traditional Chinese medicine syndromes in patients with CHB comorbid with MAFLD were mainly dominated by damp-heat accumulation syndrome， liver stagnation and spleen deficiency syndrome， and phlegm-blood stasis syndrome， with damp-heat accumulation syndrome accounting for the highest proportion （41.89%）. Compared with those without damp-heat accumulation syndrome， patients with damp-heat accumulation syndrome had significantly lower tongue proper H value， tongue coating H value， and tongue coating a^* value （P<0.05）， significantly higher tongue coating b^* value （P<0.05）， significantly increased levels of white blood cell （WBC）， red blood cell （RBC）， hemoglobin （HGB）， and glucose （GLU）， increased CAP values （P<0.05）， a higher proportion of males （P<0.05）， and a younger age （P<0.05）. Univariate and multivariate logistic regression analyses show that age， hepatitis B surface antigen （HBsAg）， diabetes， and damp-heat accumulation syndrome are independent risk factors for liver fibrosis （P<0.05）， and that damp-heat accumulation syndrome is predominantly distributed in liver fibrosis stage F0-F1. ConclusionDamp-heat accumulation syndrome is a typical syndrome in patients with CHB comorbid with MAFLD， which is significantly associated with enhanced inflammatory response， metabolic disorders， and early liver fibrosis， and is a key link in disease progression. Clinical attention and early intervention are needed.

Background: Visceral white adipose tissue (vWAT) inflammation is a critical pathology of obesity-caused heart damage and is closely associated with adipocyte endoplasmic reticulum (ER) dysfunction. Serine (or cysteine) peptidase inhibitor, clade A, member 3C (Serpina3c) has been identified as an adipokine with anti-vWAT inflammatory effects. However, it remains unclear whether Serpina3c deficiency promotion of vWAT inflammation involves adipocyte ER dysfunction and whether it further contributes to heart damage in obesity. Methods: Wild type and Serpina3c knockout (Serpina3c–/–) mice were fed a high-fat diet (HFD) for 12 weeks. An adeno-associated virus (AAV) was injected locally into epididymal white adipose tissue (eWAT) of Serpina3c–/– mice to induce eWAT-adipocyte- specific overexpression of Serpina3c (AAV-Serpina3c) or knockdown of hypoxia-inducible factor 1α (AAV-shHIF1α). In vitro experiments were performed in 3T3-L1 adipocytes. Results: Serpina3c–/– mice exhibited more severe eWAT, serum and heart inflammation after HFD feeding. Consistently, these adverse phenotypes were mitigated in AAV-Serpina3c and AAV-shHIF1α mice. Mechanistically, ER oxidoreductase 1α (Ero1α) and protein disulfide isomerase (PDI) family members PDIA3 and PDIA4 were found to be target genes of HIF1α. In the obese mice, Serpina3c deficiency caused adipocyte more hypertrophy, and activated HIF1α-Ero1α/PDI mediated ER overoxidation and ER stress in eWAT. Subsequently, this led to increased adipocyte apoptosis and chemokine production and decreased adiponectin expression, which promoted macrophage infiltration and M1 polarization in eWAT, thus exacerbating eWAT inflammation and ultimately facilitating serum and distal heart inflammation. Conclusion These findings indicate that Serpina3c is a significant regulator of adipocyte ER redox homeostasis, thus highlighting Serpina3c as a potential therapeutic target for obesity-related eWAT inflammation and heart damage.

Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

Objective:To estimate the burden of influenza-associated outpatient consultations in China from 2011 to 2021 surveillance years to provide a reference for developing influenza prevention, control strategies, and vaccination policies.Methods:Data on influenza-like illness (ILI) and virological confirmation of sentinel specimens from 2011 to 2021 surveillance years were extracted from China's national sentinel surveillance system. Generalized additive models were fitted to estimate influenza-associated excess ILI outpatient burden, accounting for seasonal baselines and meteorological factors.Results:Influenza was associated with an average of 1.66 (95% CI: 1.51-1.80) excess ILI consultations per 1 000 person-years (py) in China each year from 2011 to 2021 surveillance years. The influenza-associated outpatient burden was similar across different virus types/subtypes. Influenza A(H1N1)pdm09 led to a higher rate of influenza- associated ILI consultations [0.65 (95% CI: 0.53-0.76) per 1 000 py] compared to other types/subtypes. The age groups with the highest burdens were children aged 0-4 years and 5-14 years, with excess outpatient consultation rates of 15.23 (95% CI: 13.73-16.73) per 1 000 py and 13.53 (95% CI: 12.49-14.52) per 1 000 py, respectively. Conclusions:Influenza caused many outpatient consultations in China, particularly among children aged 0-14. Continuous influenza monitoring and disease burden assessment should be conducted, and close attention should be paid to the changing trends of various influenza virus types/subtypes. When formulating vaccination strategies, priority should be given to recommending vaccination for high-risk populations, such as children.

Objective To investigate the feasibility of hernia needle assisted suture in single-incision laparoscopic transabdominal preperitoneal repair(SIL-TAPP).Methods From February 2023 to April 2024,20 young patients with indirect inguinal hernia were treated with SIL-TAPP.A 2 cm curved incision was made at the navel,and a three channel port was inserted for transabdominal preperitoneal repair.A hernia needle was inserted into the affected side lower abdominal wall to assist in one handed suturing and closure of the peritoneum.Results All the operations were successful.The operation time was 85-125 min,with an average of(91.3±10.0)min.The closure of the peritoneum took 18-30 min,with an average of(23.4±3.2)min.Intraoperative blood loss was 5-25 ml.The Visual Analogue Scale(VAS)score at 24 h after surgery was 1-3 points.Postoperative hospitalization lasted 1-5 d,with an average of(2.4±1.0)d.After surgery,one patient had seroma in the groin area and one patient had fat liquefaction in the umbilical cord.All the patients were followed up for 8-22 months after operation,with an average of(15.3±3.4)months.No recurrence after operation or umbilical hernia was noted.Conclusion The use of hernia needle assisted suturing to close the peritoneum during SIL-TAPP surgery can reduce the difficulty of one handed suturing,especially suitable for the early stage of single-incision laparoscopic surgery.

AIM To establish the near-infrared spectroscopy quantitative models for moisture,23-acetylalismol B and 23-acetylalismol C in Alismatis Rhizoma decoction pieces.METHODS The near-infrared spectroscopy(NIRS)data were collected in 95 batches of decoction pieces,after which drying method was adopted in the content determination of moisture,HPLC was applied to determining the contents of 23-acetylalismol B and 23-acetylalismol C,the quantitative models were established by partial least squares method combined with feature extraction algorithms.RESULTS The model training determination coefficients were 0.952 6,0.958 1 and 0.920 8,along with the prediction determination coefficients of 0.930 0,0.905 2 and 0.906 4,the residual prediction deviations(PRD)of 4.00,3.58 and 3.46,and the root mean square error ratios of prediction values to calibration values(RMSEP/RMSEC)of 1.15,1.11 and 1.06,respectively.CONCLUSION The quantitative models based on NIRS exhibit good prediction effects,which can be used for the rapid quality detection of Alismatis Rhizoma decoction pieces.

As the simplest label-free single-molecule analytical technique in solution,nanopore technology has been widely used in rapid sequencing of protein and nucleic acid,and single-molecule sensing.However,the main challenge is to get this technology out of the lab and achieve automation,miniaturization as well as rapid analysis at high throughput.In this work,a new microfluidic tubing protein nanopore analysis system was designed and constructed by combining microfluidic and nanopore nanofluidic analysis techniques.An arcuate lipid bilayer was formed in the microfluidic device through lipid monolayer at the oil/water interface by developed aperture processing technology at 10 μm level.The arcuate lipid bilayer with the life span of more than 98 h had high biomimetic fluidity and biological activity by which protein channel could be produced and sealed at 18 GΩ level without leakage.When applied+40 mV potential,relative standard deviation of single proteinα-hemolysin mutant(α-HL(M113F/K147N))channel current was less than 0.16 pA(n=3)in 10 mmol/L Tris-HCl(pH 7.4)buffer containing 1 mol/L NaCl.Single-molecule detection for aptamer and its host-guest interactions with biotin in protein channel demonstrated that this microfluidic tube protein nanopore sensor could well work with high sensitivity without the need of anti-vibration table and shielding cage.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*