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.

The wear debris generated during artificial joint prosthesis service can react with bone tissues to form osteolysis,seriously affecting the life-time of artificial joint prostheses.This paper reviews,summarizes,and analyzes domestic and international research literature on the extraction,characterization,and identification of wear debris from different artificial joint materials,aiming to provide references and feasible ideas for the future construction of a systematic and hierarchical research system for artificial joint wear debris.The main findings are as follows:strong alkali protein degradation test,strong acid protein degradation test,and protease protein degradation test are the commonly used method for extracting artificial joint wear debris,and researchers have clarified the protein degradation mechanisms of these three debris extraction methods.The characterization of wear debris in-vitro and in-vivo is mostly for hip and knee joints,with a small amount involving cervical spine and ankle joints.Studies have shown that the size,quantity,shape,and volume of wear particles are influenced by factors such as joint type,contact area,material selection,and implantation time.Both domestic and international studies have conducted characterization research on wear debris after in-vitro simulation testing,but there is still a lack of wear debris characterization analysis of clinical retrievals in China.Currently,most research is on the recognition of wear debris in the traditional mechanical field,but research on the intelligent recognition of artificial joint wear debris is relatively few,indicating that there is a certain lag in the application of computer technology in the field of artificial joint wear debris recognition.

A 14-year-old boy was admitted to the hospital due to a single episode of afebrile seizure and four hours of impaired consciousness. Three months prior to admission, he had a history of bilateral uveitis. Cerebrospinal fluid analysis revealed a mild elevation in white blood cell count. Cranial magnetic resonance imaging and contrast-enhanced scans showed multiple abnormal signals in both cerebral hemispheres, with punctate and nodular enhancement. Susceptibility-weighted imaging revealed multiple punctate hemorrhages within lesions in the bilateral frontal and left parietal lobes, suggestive of vasculitis. Brain biopsy demonstrated inflammatory granulomatous lesions. No secondary causes were identified, and the final diagnosis was granulomatous primary central nervous system vasculitis. The patient's condition improved after treatment with methylprednisolone sodium succinate and mycophenolate mofetil. This report describes a rare case of granulomatous central nervous system vasculitis in a child and provides valuable insights for the diagnosis and treatment of this disease.
Humans ; Male ; Vasculitis, Central Nervous System/diagnosis* ; Adolescent ; Magnetic Resonance Imaging ; Granuloma/diagnosis*

The wear debris generated during artificial joint prosthesis service can react with bone tissues to form osteolysis,seriously affecting the life-time of artificial joint prostheses.This paper reviews,summarizes,and analyzes domestic and international research literature on the extraction,characterization,and identification of wear debris from different artificial joint materials,aiming to provide references and feasible ideas for the future construction of a systematic and hierarchical research system for artificial joint wear debris.The main findings are as follows:strong alkali protein degradation test,strong acid protein degradation test,and protease protein degradation test are the commonly used method for extracting artificial joint wear debris,and researchers have clarified the protein degradation mechanisms of these three debris extraction methods.The characterization of wear debris in-vitro and in-vivo is mostly for hip and knee joints,with a small amount involving cervical spine and ankle joints.Studies have shown that the size,quantity,shape,and volume of wear particles are influenced by factors such as joint type,contact area,material selection,and implantation time.Both domestic and international studies have conducted characterization research on wear debris after in-vitro simulation testing,but there is still a lack of wear debris characterization analysis of clinical retrievals in China.Currently,most research is on the recognition of wear debris in the traditional mechanical field,but research on the intelligent recognition of artificial joint wear debris is relatively few,indicating that there is a certain lag in the application of computer technology in the field of artificial joint wear debris recognition.

Objective To investigate the infection status and changing trend of hepatitis C virus(HCV)infection in hospitalized patients in medical institutions,and provide reference for formulating HCV infection prevention and control strategies.Methods HCV infection surveillance results from cross-sectional survey data reported to China Healthcare-associated Infection(HAI)Surveillance System in 2020 were summarized and analyzed,HCV positive was serum anti-HCV positive or HCV RNA positive,survey result was compared with the survey results from 2003.Results In 2020,1 071 368 inpatients in 1 573 hospitals were surveyed,738 535 of whom underwent HCV test,4 014 patients were infected with HCV,with a detection rate of 68.93％and a HCV positive rate of 0.54％.The positive rate of HCV in male and female patients were 0.60％and 0.48％,respectively,with a statistically sig-nificant difference(x2=47.18,P＜0.001).The HCV positive rate in the 50-＜60 age group was the highest(0.76％),followed by the 40-＜50 age group(0.71％).Difference among all age groups was statistically signifi-cant(x2=696.74,P＜0.001).In 2003,91 113 inpatients were surveyed.35 145 of whom underwent HCV test,resulting in a detection rate of 38.57％;775 patients were infected with HCV,with a positive rate of 2.21％.In 2020,HCV positive rates in hospitals of different scales were 0.46％-0.63％,with the highest in hospital with bed numbers ranging 600-899.Patients'HCV positive rates in hospitals of different scales was statistically signifi-cant(X2=35.34,P＜0.001).In 2020,12 provinces/municipalities had over 10 000 patients underwent HCV-rela-ted test,and HCV positive rates ranged 0.19％-0.81％,with the highest rate from Hainan Province.HCV posi-tive rates in different departments were 0.06％-0.82％,with the lowest positive rate in the department of pedia-trics and the highest in the department of internal medicine.In 2003 and 2020,HCV positive rates in the depart-ment of infectious diseases were the highest,being 7.95％and 3.48％,respectively.Followed by departments of orthopedics(7.72％),gastroenterology(3.77％),nephrology(3.57％)and general intensive care unit(ICU,3.10％)in 2003,as well as departments of gastroenterology(1.35％),nephrology(1.18％),endocrinology(0.91％),and general intensive care unit(ICU,0.79％)in 2020.Conclusion Compared with 2003,HCV positive rate decreased significantly in 2020.HCV infected patients were mainly from the department of infectious diseases,followed by departments of gastroenterology,nephrology and general ICU.HCV infection positive rate varies with gender,age,and region.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

OBJECTIVE: To investigate the expression of pyruvate kinase M2 (PKM2) in bone marrow mesenchymal stem cells (BMSCs) in myeloma bone disease (MBD) and its effect on osteogenic and adipogenic differentiation of BMSCs. METHODS: BMSCs were isolated from bone marrow of five patients with multiple myeloma (MM) (MM group) and five with iron deficiency anemia (control group) for culture and identification. The expression of PKM2 protein were compared between the two groups. The differences between osteogenic and adipogenic differentiation of BMSCs were assessed by using alkaline phosphatase (ALP) and oil red O staining, and detecting marker genes of osteogenesis and adipogenesis. The effect of MM cell line (RPMI-8226) and BMSCs co-culture on the expression of PKM2 was explored. Functional analysis was performed to investigate the correlations of PKM2 expression of MM-derived BMSCs with osteogenic and adipogenic differentiation by employing PKM2 activator and inhibitor. The role of orlistat was explored in regulating PKM2 expression, osteogenic and adipogenic differentiation of MM-derived BMSCs. RESULTS: Compared with control, MM-originated BMSCs possessed the ability of increased adipogenic and decreased osteogenic differentiation, and higher level of PKM2 protein. Co-culture of MM cells with BMSCs markedly up-regulated the expression of PKM2 of BMSCs. Up-regulation of PKM2 expression could promote adipogenic differentiation and inhibit osteogenic differentiation of MM-derived BMSCs, while down-regulation of PKM2 showed opposite effect. Orlistat significantly promoted osteogenic differentiation in MM-derived BMSCs via inhibiting the expression of PKM2. CONCLUSION The overexpression of PKM2 can induce the inhibition of osteogenic differentiation of BMSCs in MBD. Orlistat can promote the osteogenic differentiation of BMSCs via inhibiting the expression of PKM2, indicating a potential novel agent of anti-MBD therapy.
Humans ; Adipogenesis ; Bone Diseases/metabolism* ; Bone Marrow Cells ; Cell Differentiation ; Cells, Cultured ; Mesenchymal Stem Cells/physiology* ; Multiple Myeloma/metabolism* ; Orlistat/pharmacology* ; Osteogenesis/genetics*

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.