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 explore the role and mechanism of RNA m6A methyltransferase Wilms'tumor 1-associated protein(WTAP)in epithelial-mesenchymal transition(EMT)of glioblastoma cells and its association with transcription factor JUNB.Methods(1)Based on the Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases,the expression levels of transforming growth factor β(TGF-β),WTAP,and JUNB in glioblastoma multiforme(GBM)and normal brain tissues were analyzed,as well as their diagnostic and prognostic values for GBM.The correlation of TGF-β,WTAP,and JUNB with gliomas of different WHO grades was analyzed using the Chinese Glioma Genome Atlas(CGGA)database.Spearman correlation analysis was performed to assess the correlation between TGF-β and m6A methyltransferases.(2)An EMT model was established in human astrocytoma U87-MG cells through TGF-β1 induction.qRT-PCR and Western blotting were employed to detect the expression levels of WTAP,JUNB,matrix metalloproteinase 2(MMP2),and N-cadherin.The migration capacity of U87-MG cells was evaluated by wound-healing and Transwell assays.An m6A RNA methylation quantification kit(colorimetric)was used to detect RNA m6A methylation modification levels.A stable cell line with low expression of WTAP was constructed to investigate the effects of WTAP knockdown on the migration ability of U87-MG cells,as well as the expression of JUNB.(3)A protein-protein interaction network was constructed using STRING database and GeneMANIA database,followed by gene ontology(GO)and KEGG pathway enrichment analyses to explore the biological processes,molecular functions,cellular components,and signaling pathways potentially involved in TGF-β/WTAP/JUNB.Gene set enrichment analysis(GSEA)was performed on JUNB-related genes to investigate their potential downstream signaling pathways.Results(1)The expression levels of TGF-β,WTAP,and JUNB were significantly higher in GBM(P<0.001),positively correlated with WHO grades of glioma(P<0.001).Glioma patients with high expression of all three genes had shorter overall and disease-free survival(P<0.001).Spearman analysis showed that the expression of TGF-β in GBM was positively correlated with WTAP(r=0.175,P=0.023),but no significant correlation with other m6A methyltransferases(P>0.05).(2)After TGF-β1 treatment,the level of m6A methylation modification of total RNA in U87-MG cells significantly increased(P<0.001).Wound-healing assay and Transwell assay results showed that the migration ability of U87-MG cells was significantly increased after TGF-β1 treatment(P<0.01),while WTAP knockdown significantly reduced the migration ability of U87-MG cells(P<0.01).qRT-PCR and Western blotting results showed that the mRNA and protein expression levels of WTAP,N-Cadherin,MMP2,and JUNB in U87-MG cells were significantly increased after 48 h of TGF-β1 induction(P<0.001),while WTAP knockdown significantly reduced the mRNA and protein expression of JUNB(P<0.001).(3)The TGF-β/WTAP/JUNB-related protein-protein interaction network was constructed,which was primary involved in mRNA modification and EMT.GSEA results showed that JUNB-related signaling pathways were closely associated with glioma malignant progression.Conclusions TGF-β,WTAP,and JUNB are all associated with GBM malignant progression and poor patient prognosis.TGF-β may enhance total RNA m6A modification by promoting the expression of m6A methyltransferase WTAP,and WTAP subsquentaly upregulates transcription factor JUNB,thereby promoting EMT and malignant progression of GBM.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To investigate the effect of operation mode,thickness,and number of implanted electrode leads on tricuspid regurgitation.Methods This was a single-center retrospective study.Patients who received their first cardiac implantable electronic device at the Second Affiliated Hospital of Harbin Medical University from January 2019 to January 2024 and were followed up within(10±4)months were continuously enrolled.General clinical data,preoperative and outpatient follow-up echocardiography,and other indicators were collected.According to the different operation modes,patients were divided into delivery sheath group,support wire group,and delivery sheath combined support wire group.Under the premise of only one electrode wire crossing the tricuspid valve,according to the different thicknesses of the electrode wire,they were divided into 3830 69 group(4.1 F),5076 58/Solia S60 group(7 F),and 6935M-65cm defibrillator group(9 F).The number of electrode wires was divided into 3830 69 subgroup and 6935M-65cm defibrillator subgroup under the premise of balanced operation mode and electrode material.The changes in tricuspid valve regurgitation were compared in each group.Results A total of 219 patients,aged(65.92±12.04)years,were enrolled.There was no difference in tricuspid valve regurgitation in the 6935M-65cm defibrillator subgroup before implantation(all P＞0.05).In the 3830 69 subgroup,there was a higher proportion of severe regurgitation in the two-electrode group before implantation(P=0.013).In comparison with the change in tricuspid valve regurgitation before electrode wire implantation and during follow-up,the regurgitation of the tricuspid valve in the 6935M-65cm defibrillator subgroup with≥2 electrodes was unexpectedly improved compared to that in the group with one electrode,and the regurgitation of the valve in the group with one electrode was more severe than that in the group with ≥ 2 electrodes implantation(P=0.019).Conclusions The operation mode and thickness of the implanted electrode lead did not cause significant differences in tricuspid valve regurgitation.Single implantation of a 6935M-65cm defibrillator electrode will lead to increased tricuspid regurgitation,and the effect brought by combination with physiological pacing will offset the adverse effects of electrode leads on the valve,providing directional evidence for future implantation strategy selection.

Objective To design a centrifugal agtomization principle-based disinfection and disinsection device for plateau areas.Methods A disinfection and disinsection device was developed based on centrifugal atomization principle,which was composed of a spraying body,lifting and rotating mechanisms,an electrical control system,a spray tank and a sprayer carriage.The spraying body consisted of spraying components,a motor,an air blower,a fan and etc,and the spraying components adopted the structural form of multi-layer disc stacking to realize the atomization of liquid medicine;the lifting mechanism implemented up-and-down adjustment of the air blower through an electric actuartor,and the rotating mechanism executed left-and-right adjustment of the air blower thrgouth the worm gear motor and limit switch;the electrical control system was made up of a power source,electrical devices,a distribution system and a control system,in which a lead-acid battery pack was used for power supply and a DGUS touch screen and a DCS001 controller were involved in the control system;the spray tank was formed of a tank body,a needle valve,a water pump,float switch,etc;the sprayer carriage comprised a frame,a pusher,two sealing plates and four wheels.Some disc samples with different diameters were trial produced,and comparison experiments were carried out to investigate the relationship between disc diameter,motor speed,spray flow rate and atomization effect;a prototype was manufactured for performance testing of the device.Results The disc diameter and motor speed were inversely proportional to the droplet size;the spray flow rate was directly proportional to the droplet size,when the spray flow rate increased by 60%,the increment of the droplet size was restrained within 2%to 11%.The prototype test results indicated that the device could be used for ultra-low-volume disinfection and insecticide in plateau areas,with the D50 and D90 of the droplet size being 31 and 48 μm,respectively.Conclusion The device developed gains advantages in atomiztion,and meets the requirements for epidemic prevention,disinfection and disinsection in plateau areas.[Chinese Medical Equipment Journal,2025,46(4):35-39]

Objective To explore the application of goal-directed fluid therapy based on pulse pressure variation rate(PPV)combined with low central venous pressure(LCVP)technique in liver surgery.Methods A total of 86 patients who underwent liver lobe/segment resection in our hospital from January 2022 to December 2023 were included,and randomly divided into two groups by random sequence method.Patients in the conventional group were treated with LCVP technique,while patients in the test group were given PPV goal-directed intervention on the basis of the conventional group.The surgical indicators,hemodynamic indicators,cognitive function,adverse reactions and recovery of gastrointestinal function of patients in the two groups were compared.Results There was no statistically significant difference in the operation time,Pringle maneuver time,first postoperative exhausting time or first postoperative defecation time of patients between the two groups(P>0.05).However,the intraoperative blood loss,intraoperative fluid infusion volume and hospital stay of patients in the test group were all less/shorter than those in the conventional group(P<0.05).Compared with the time point of T0,patients in the two groups showed increased heart rate(HR)but decreased mean arterial pressure(MAP)and central venous pressure(CVP)at time points of T1 and T2(P<0.05).There was no statistically significant difference in the HR or MAP of patients between the two groups at time points of T0,T1,T2 and T3(P>0.05).At time points of T1 and T2,the CVP of patients in the test group was lower than that in the conventional group(P<0.05).One day after operation,the mini-mental state examination(MMSE)score of patients in the test group was higher than that in the conventional group(P<0.05).The MMSE scores 7 days after operation of patients in the two groups were higher than those 1 day after operation(P<0.05).Patients in the test group had a lower total incidence of adverse reactions and a shorter recovery time of gastrointestinal function than those in the conventional group(P<0.05).Conclusion The goal-directed fluid therapy based on PPV combined with LCVP technique has a good application effect in liver surgery,which can reduce intraoperative blood loss and fluid infusion volume of patients,shorten hospital stay,increase hemodynamic stability,improve postoperative cognitive dysfunction,and promote the recovery of gastrointestinal function,with a relatively high treatment safety.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*

An 11-year-old boy presented with erythematous plaques over the bilateral mandibular and mental regions for 2 years, accompanied by cough and dyspnea for more than 2 months. Chest computed tomography angiography revealed marked stenosis of the right pulmonary artery, irregular aortic caliber, and aortic wall thickening. Histopathological examination of the skin lesion, including immunohistochemistry and special stains, confirmed a chronic suppurative inflammation. Whole-exome sequencing was negative. A final diagnosis of granuloma faciale and Takayasu arteritis was established. Combination therapy with systemic tocilizumab, prednisone, and methotrexate, along with topical 0.1% tacrolimus ointment, resulted in a favorable clinical response. This report summarizes the clinical features of a pediatric case of granuloma faciale and Takayasu arteritis and reviews the etiology, diagnostic approach, and current treatment strategies for the disorders, aiming to enhance clinicians' understanding of these conditions.
Humans ; Male ; Child ; Takayasu Arteritis/diagnosis* ; Facial Dermatoses/diagnosis*