Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

OBJECTIVE: To evaluate the anti-hepatocellular carcinoma (HCC) activity of total alkaloids from Gelsemium elegans Benth. (TAG) in vivo and in vitro and to elucidate their potential mechanisms of action through transcriptomic analysis. METHODS: TAG extraction was conducted, and the primary components were quantified using high-performance liquid chromatography (HPLC). The effects of TAG (100, 150, and 200 µg/mL) on various tumor cells, including SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116, were assessed. Effects of TAG on HCC proliferation and apoptosis were detected by colony formation assays and cell stainings. Caspase-3, Bcl-2, and Bax protein levels were detected by Western blotting. In vivo, a tumor xenograft model was developed using H22 cells. Totally 40 Kunming mice were randomly assigned to model, cyclophosphamide (20 mg/kg), TAG low-dose (TAG-L, 0.5 mg/kg), and TAG high-dose (TAG-H, 1 mg/kg) groups, with 10 mice in each group. Tumor volume, body weight, and tumor weight were recorded and compared during 14-day treatment. Immune organ index were calculated. Tissue changes were oberseved by hematoxylin and eosin staining and immunohistochemistry. Additionally, transcriptomic and metabolomic analyses, as well as quatitative real-time polymerase chain reaction (RT-qPCR), were performed to detect mRNA and metabolite expressions. RESULTS: HPLC successfully identified the components of TAG extraction. Live cell imaging and analysis, along with cell viability assays, demonstrated that TAG inhibited the proliferation of SMMC-7721, HepG2, H22, CAL27, MCF7, HT29, and HCT116 cells. Colony formation assays, Hoechst 33258 staining, Rhodamine 123 staining, and Western blotting revealed that TAG not only inhibited HCC proliferation but also promoted apoptosis (P<0.05). In vivo experiments showed that TAG inhibited the growth of solid tumors in HCC in mice (P<0.05). Transcriptomic analysis and RT-qPCR indicated that the inhibition of HCC by TAG was associated with the regulation of the key gene CXCL13. CONCLUSION TAG inhibits HCC both in vivo and in vitro, with its inhibitory effect linked to the regulation of the key gene CXCL13.
Animals ; Apoptosis/drug effects* ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Humans ; Alkaloids/therapeutic use* ; Gelsemium/chemistry* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Mice ; Xenograft Model Antitumor Assays

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major health concern in northwest China; however, the impact of particulate matter (PM) exposure during sand-dust storms (SDS) remains poorly understood. Therefore, this study aimed to investigate the association between PM exposure on SDS days and COPD hospitalization risk in arid regions. METHODS: Data on daily COPD hospitalizations were collected from 323 hospitals from 2018 to 2022, along with the corresponding air pollutant and meteorological data for each city in Gansu Province. Employing a space-time-stratified case-crossover design and conditional Poisson regression, we analyzed 265,379 COPD hospitalizations. RESULTS: PM exposure during SDS days significantly increased COPD hospitalization risk [relative risk ( RR) for PM _2.5, lag 3:1.028, 95% confidence interval ( CI): 1.021-1.034], particularly among men and the elderly, and during the cold season. The burden of PM exposure on COPD hospitalization was substantially high in Northwest China, especially in the arid and semi-arid regions. CONCLUSION Our findings revealed a positive correlation between PM exposure during SDS episodes and elevated hospitalization rates for COPD in arid and semi-arid zones in China. This highlights the urgency of developing region-specific public health strategies to address adverse respiratory outcomes associated with SDS-related air quality deterioration.
Humans ; China/epidemiology* ; Pulmonary Disease, Chronic Obstructive/chemically induced* ; Particulate Matter/analysis* ; Hospitalization/statistics & numerical data* ; Male ; Female ; Middle Aged ; Aged ; Air Pollutants/analysis* ; Environmental Exposure/adverse effects* ; Spatio-Temporal Analysis ; Adult ; Sand ; Air Pollution

Twelve pre-processing protocols for formalin-fixed paraffin-embedded(FFPE)tissue samples were developed by orthogonal experimental design,incorporating different dewaxing buffers(Triton X-100 and xylene),lysis buffers(TFE and RapiGest),and enzyme digestion methods(iST,SP3,and FASP)to explore the optimal experimental conditions.These protocols were assessed based on protein and peptide identification depth,identification stability,and quantitative levels of protein abundance.The results indicated that Triton X-100 and xylene minimally impacted proteomics identification,whereas the TFE lysis buffer and iST digestion method significantly enhanced the proteomics analysis of FFPE samples.Considering the potential toxicity of xylene,the TTI protocol based on Triton X-100,TFE,and iST was determined to be the optimal choice.This protocol exhibited the best repeatability and stability,and a higher number of proteins associated with significant biological functions were identified.In conclusion,the established TTI protocol offered an efficient and comprehensive approach for proteomic analysis of FFPE samples,significantly enhancing the repeatability and stability of protein identification.

Objective: To analyze the serological characteristics of anti-Mur antibodies and investigate the distribution frequency of the Mur antigen among voluntary blood donors in Shiyan, thereby providing a basis for guiding clinical transfusion and establishing a Mur blood type database. Methods: ABO blood grouping of donors and patients was performed using an automated blood typing analyzer and the gel card method, respectively. Unexpected antibody screening and identification were performed using the saline, tube anti-human globulin, and polybrene methods. The specificity of anti-Mur antibodies was confirmed using Fisher's exact probability test. Plasma treated with 2-mercaptoethanol was used to distinguish IgM and IgG antibodies. IgM and IgG anti-Mur titers were determined by the saline tube method and the anti-human globulin tube method, respectively, at 4℃, room temperature, and 37℃. A total of 1 659 donor red blood cell samples were initially screened for the Mur antigen phenotype using three samples of human-derived anti-Mur plasma by the micro-tube method. Donors who tested positive for Mur antigen were further tested by the direct antiglobulin test (DAT); those with negative results were confirmed for Mur antigen by the gel card and polybrene methods. Results: Three blood samples were identified to contain mixed IgG and IgM anti-Mur antibodies. The titers of both IgM and IgG anti-Mur antibodies were highest at 4℃, intermediate at room temperature, and lowest at 37℃. The positive frequency of the Mur antigen among voluntary blood donors in Shiyan was 1.99% (33/1 659). Conclusion: anti-Mur antibodies were detected in both blood donors and patients in our region. The Mur antigen shows a certain distribution frequency among voluntary blood donors in Shiyan. Screening for the Mur blood type and establishing a corresponding database could enhance transfusion safety.

Objective:To explore patterns of traditional Chinese medicine (TCM) use among patients with inflammatory bowel disease (IBD) in Jiangsu Province, China from 2019 to 2023.Methods:Using data from the IBD health data platform of the National Healthcare Big Data (Eastern) Center, a retrospective cohort study was conducted. We performed descriptive analyses on hospitalised patients diagnosed with IBD between 2019 and 2023, who received TCM treatment.Results:The study included 11 095 case records from 4 760 patients, with TCM diagnoses primarily indicating diarrhoea and abdominal pain. Ulcerative colitis (UC) accounted for 4 782 hospitalizations (3 103 patients), while Crohn's disease (CD) accounted for 6 313 hospitalizations (1 657 patients). Patient demographics showed a trend towards younger age and a higher proportion of males. Treatment utilisation was highest in southern Jiangsu compared with the central and northern regions. In terms of disease burden, all treatment costs showed a downward trend. In terms of external TCM therapies, UC patients tend to prefer plasters and enemas, while CD patients are more inclined to use acupuncture. Regarding herbal medicine, licorice, white atractylodes, and white peony root are commonly used single herbs for IBD patients.Conclusions:The number of IBD patients treated with TCM in Jiangsu Province has steadily increased from 2019 to 2023. It is important to identify effective TCM treatment methods to reduce the burden of patients.

Objective:To compare the efficacy and safety of crisaborole ointment 2% versus pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged 2 years or older.Methods:A multicenter, randomized, open-label, controlled clinical trial was conducted. A total of 120 pediatric patients aged 2 - 17 years with mild to moderate atopic dermatitis were enrolled from departments of dermatology of 8 hospitals in China between March 2022 and February 2023. The participants were randomly assigned in a 1∶1 ratio to the crisaborole group and the pimecrolimus group, and received the treatment with crisaborole ointment 2% and pimecrolimus cream 1% respectively, twice a day for 4 weeks. Visits were scheduled at baseline/on day 1, as well as on days 8, 15, and 29. The primary efficacy outcome was the percentage of patients achieving the Investigator's Static Global Assessment (ISGA) success (defined as clear [0] or almost clear [1] on the ISGA scale, combined with ≥ 2‐grade improvement from baseline) on day 29. The secondary efficacy outcomes included changes in the Eczema Area and Severity Index (EASI) total scores from baseline to day 29, percentages of patients achieving ISGA improvement (defined as clear [0] or almost clear [1] on the ISGA scale), as well as changes in the Peak Pruritus Numerical Rating Scale (NRS) scores, Dermatology Life Quality Index (DLQI) /Infants' Dermatology Life Quality Index (IDLQI) /Children's Dermatology Life Quality Index (CDLQI) scores, and in the Dermatitis Family Impact (DFI) scores. Drug safety was evaluated according to the incidence of adverse events. Categorical data were compared using the chi-square test. Since measurement data did not follow a normal distribution, the rank sum test was used for comparisons of measurement data between groups.Results:A total of 106 children with mild to moderate atopic dermatitis were included in the per-protocol analysis set, with 52 in the crisaborole group (26 males and 26 females) and 54 in the pimecrolimus group (27 males and 27 females). There were no significant differences in age, disease duration, ISGA and EASI scores at baseline between the two groups (all P > 0.05). On day 29, 22 patients (42.31%) in the crisaborole group and 25 (46.30%) in the pimecrolimus group achieved ISGA success, with no significant difference between the two groups ( χ2 = 0.17, P = 0.68) ; 35 patients (67.31%) in the crisaborole group and 45 (83.33%) in the pimecrolimus group achieved ISGA improvement, also with no significant difference between the two groups ( χ2 = 3.68, P = 0.06) ; additionally, there were no significant differences in the EASI, pruritus NRS, DLQI/IDLQI/CDLQI, or DFI scores between the two groups (all P > 0.05). Adverse reactions to the two topical agents were mainly local reactions such as mild to moderate pain, itching, or worsening of itching, and no obvious systemic adverse reactions occurred. The incidence of drug-related adverse reactions was 46.15% (24 cases) in the crisaborole group and 37.04% (20 cases) in the pimecrolimus group, with no significant difference between the two groups ( χ2 = 0.91, P = 0.34) . Conclusion:The efficacy of crisaborole ointment 2% was comparable to that of pimecrolimus cream 1% in the treatment of mild to moderate atopic dermatitis in children aged ≥ 2 years, and it yielded early and rapid improvement in the quality of life of patients and their families, with good safety and tolerability profiles.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

The mammary gland is one of the most important glands in human body, and the abnormal changes of its tissue mechanics are often closely related to the occurrence and development of mammary gland diseases. With the development of two new interdisciplines, biomechanics and mechanobiology, their theoretical research results have been gradually transformed into clinical applications, resulting in two new clinical disciplines, mechanodiagnostics and mechanotherapy. However, many clinicians still lack a systematic and in-depth understanding of the biomechanical characteristics and mechanobiology of breast tissue, and their potential value in the clinical diagnosis and treatment of breast diseases. In view of this, we elaborated the evolution law of the biomechanical characteristics and mechanobiological mechanism of breast diseases from four aspects: breast biomechanics, breast mechanobiology, breast mechanodiagnostics, and breast mechanotherapy, analyzed their role in the occurrence and development of breast diseases, and discussed the mechanical principles involved in the traditional diagnosis and treatment of breast diseases, to provide new ideas and schemes for the diagnosis and treatment of breast diseases.