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.

This study investigates the genetic diversity and evolutionary relationships of different Artemisia argyi germplasm resources to provide a basis for germplasm identification, variety selection, and resource protection. A total of 192 germplasm resources of A. argyi were studied, and EST-based simple sequence repeat(EST-SSR) primers were designed based on transcriptomic data of A. argyi. Polymerase chain reaction(PCR) amplification was performed on these resources, followed by fluorescence capillary electrophoresis to detect genetic diversity and construct DNA fingerprints. From 197 pairs of primers designed, 28 pairs with polymorphic and clear bands were selected. A total of 278 alleles were detected, with an average of 9.900 0 alleles per primer pair and an average effective number of alleles of 1.407 2. The Shannon's diversity index(I) for the A. argyi germplasm resources ranged from 0.148 1 to 0.418 0, with an average of 0.255 7. The polymorphism information content(PIC) ranged from 0.454 5 to 0.878 0, with an average of 0.766 9, showing high polymorphism. Cluster analysis divided the A. argyi germplasm resources into three major groups: Group Ⅰ contained 136 germplasm samples, Group Ⅱ contained 45, and Group Ⅲ contained 11. Principal component analysis also divided the resources into three groups, which was generally consistent with the clustering results. Mantel test results showed that the genetic variation in A. argyi populations was to some extent influenced by geographic distance, but the effect was minimal. Structure analysis showed that 190 germplasm materials had Q≥ 0.6, indicating that these germplasm materials had a relatively homogeneous genetic origin. Furthermore, 8 core primer pairs were selected from the 28 designed primers, which could distinguish various germplasm types. Using these 8 core primers, DNA fingerprints for the 192 A. argyi germplasm resources were successfully constructed. EST-SSR molecular markers can be used to study the genetic diversity and phylogenetic relationships of A. argyi, providing theoretical support for the identification and molecular-assisted breeding of A. argyi germplasm resources.
Artemisia/classification* ; Microsatellite Repeats ; Genetic Variation ; Expressed Sequence Tags ; DNA Fingerprinting ; Phylogeny ; Polymorphism, Genetic ; DNA, Plant/genetics* ; Genetic Markers

This study aims to explore the mechanism through which Yishen Jiangtang Decoction(YSJTD) regulates endoplasmic reticulum stress(ERS)-mediated NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome to improve diabetic nephropathy(DN) in db/db mice. Thirty db/db mice were randomly divided into the model group, YSJTD group, ERS inhibitor 4-phenylbutyric acid(4-PBA) group, with 10 mice in each group. Additionally, 10 db/m mice were selected as the control group. The YSJTD group was orally administered YSJTD at a dose of 0.01 mL·g~(-1), the 4-PBA group was orally administered 4-PBA at a dose of 0.5 mg·g~(-1), and the control and model groups were given an equal volume of carboxylmethyl cellulose sodium. The treatments were administered once daily for 8 weeks. Food intake, water consumption, and body weight were recorded every 2 weeks. After the intervention, fasting blood glucose(FBG), glycosylated hemoglobin(HbA1c), urine microalbumin(U-mALB), 24-hour urine volume, serum creatinine(Scr), and blood urea nitrogen(BUN) were measured. Inflammatory markers interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected using the enzyme-linked immunosorbent assay(ELISA). Renal pathology was assessed through hematoxylin-eosin(HE), periodic acid-Schiff(PAS), and Masson staining, and transmission electron microscopy(TEM). Western blot was used to detect the expression levels of glucose-regulated protein 78(GRP78), C/EBP homologous protein(CHOP), NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), cysteinyl aspartate-specific proteinase(caspase-1), and gasdermin D(GSDMD) in kidney tissues. The results showed that compared to the control group, the model group exhibited poor general condition, increased weight and food and water intake, and significantly higher levels of FBG, HbA1c, U-mALB, kidney index, 24-hour urine volume, IL-1β, and IL-18. Compared to the model group, the YSJTD and 4-PBA groups showed improved general condition, increased body weight, decreased food intake, and lower levels of FBG, U-mALB, kidney index, 24-hour urine volume, and IL-1β. Specifically, the YSJTD group showed a significant reduction in IL-18 levels compared to the model group, while the 4-PBA group exhibited decreased water intake and HbA1c levels compared to the model group. Although there was a decreasing trend in water intake and HbA1c in the YSJTD group, the differences were not statistically significant. No significant differences were observed in BUN, Scr, and kidney weight among the groups. Renal pathology revealed that the model group exhibited more severe renal damage compared to the control group. Kidney sections from the model group showed diffuse mesangial proliferation in the glomeruli, tubular edema, tubular dilation, significant inflammatory cell infiltration in the interstitium, and increased glycogen staining and blue collagen deposition in the basement membrane. In contrast, the YSJTD and 4-PBA groups showed varying degrees of improvement in renal damage, glycogen staining, and collagen deposition, with the YSJTD group showing more significant improvements. TEM analysis indicated that the model group had extensive cytoplasmic edema, homogeneous thickening of the basement membrane, fewer foot processes, and widening of fused foot processes. In the YSJTD and 4-PBA groups, cytoplasmic swelling of renal tissues was reduced, the basement membrane remained intact and uniform, and foot process fusion improved.Western blot results indicated that compared to the control group, the model group showed upregulation of GRP78, CHOP, GSDMD, NLRP3, ASC, and caspase-1 expression. In contrast, both the YSJTD and 4-PBA groups showed downregulation of these markers compared to the model group. These findings suggest that YSJTD exerts a protective effect against DN by alleviating NLRP3 inflammasome activation through the inhibition of ERS, thereby improving the inflammatory response in db/db DN mice.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Diabetic Nephropathies/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Inflammasomes/drug effects* ; Male ; Kidney/pathology* ; Endoplasmic Reticulum Chaperone BiP ; Humans ; Interleukin-18/genetics* ; Mice, Inbred C57BL

To improve the quality evaluation system of Hibisci Mutabilis Folium, this study established high performance liquid chromatography(HPLC) fingerprints of Hibisci Mutabilis Folium and evaluated the quality differences of medicinal materials from different places of production by chemometrics. Furthermore, a content measurement method of differential components was established based on quantitative analysis of multi-components by single-marker(QAMS). The fingerprints of 17 batches of Hibisci Mutabilis Folium from different places of production were constructed, with a total of 19 common peaks marked and seven components confirmed. The similarity between the sample fingerprints and the reference fingerprints ranged from 0.890 to 0.974. By utilizing principal component analysis(PCA), hierarchical cluster analysis(HCA), and orthogonal partial least squares-discriminant analysis(OPLS-DA), the chemical patterns of fingerprints were identified. Five components that could be used to evaluate the quality differences of Hibisci Mutabilis Folium were screened, namely peak 6(quercetin 3-O-β-robinobioside), peak 7(rutin), peak 9(kaempferol-3-O-β-robinobioside), peak 10(kaempferol-3-O-rutinoside), and peak 14(tiliroside). The relative correction factors of isoquercitrin, kaempferol-3-O-β-robinobioside, kaempferol-3-O-rutinoside, kaempferol-3-O-β-D-glucoside, and tiliroside were measured with rutin as the internal reference. The QAMS method was established for the content measurement of six flavonoids, and the results showed there was no significant difference compared to the results obtained by an external standard method. In summary, the HPLC fingerprints and QAMS method established in the study, demonstrating stability and accuracy, can provide a reference for the overall quality evaluation of Hibisci Mutabilis Folium.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Principal Component Analysis

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

OBJECTIVES: To investigate the prognostic value of molecular minimal residual disease (Mol-MRD) monitored before and after allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric acute myeloid leukemia (AML). METHODS: Clinical data of 71 pediatric AML patients who underwent HSCT between August 2016 and December 2023 were analyzed. Mol-MRD levels were dynamically monitored in MRD-positive patients, and survival outcomes were evaluated. RESULTS: No significant difference in the 3-year overall survival (OS) rate was observed between patients with pre-HSCT Mol-MRD ≥0.01% and <0.01% (77.3% ± 8.9% vs 80.4% ± 7.9%, P=0.705). However, patients with pre-HSCT Mol-MRD <1.75% had a significantly higher 3-year OS rate than those with Mol-MRD ≥1.75% (86.6% ± 5.6% vs 44.4% ± 16.6%, P=0.020). The median Mol-MRD level in long-term survivors was significantly lower than in non-survivors [0.61% (range: 0.04%-51.58%)] vs 10.60% (range: 1.90%-19.75%), P=0.035]. Concurrent flow cytometry-based MRD positivity was significantly higher in non-survivors (80% vs 24%, P=0.039). There was no significant difference in the 3-year overall survival rate between patients with Mol-MRD ≥0.01% and those with <0.01% at 30 days post-HSCT (P=0.527). For children with Mol-MRD <0.22% at 30 days post-HSCT, the 3-year overall survival rate was 80.4% ± 5.9%, showing no significant difference compared to those with molecular negativity (87.0% ± 7.0%) (P=0.523). CONCLUSIONS Patients with pre-HSCT Mol-MRD <1.75% or post-HSCT Mol-MRD <0.22% may achieve long-term survival outcomes comparable to Mol-MRD-negative cases through HSCT and targeted interventions.
Humans ; Hematopoietic Stem Cell Transplantation ; Neoplasm, Residual ; Leukemia, Myeloid, Acute/genetics* ; Child ; Male ; Female ; Child, Preschool ; Prognosis ; Adolescent ; Infant ; Transplantation, Homologous

OBJECTIVE: To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion. METHODS: Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively. RESULTS: The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984). CONCLUSION The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans ; Lymphoma, T-Cell, Peripheral/pathology* ; Prognosis ; Retrospective Studies ; Central Nervous System Neoplasms/pathology* ; Neoplasm Invasiveness ; Male ; Female ; Central Nervous System/pathology* ; Middle Aged ; Adult

OBJECTIVE: To analyze the factors associated with mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with severe aplastic anemia (SAA). METHODS: The clinical data of 90 children with SAA who received allo-HSCT in the Department of Hematology, Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from August 2016 to July 2023 were collected. The clinical features and causes of death were analyzed retrospectively. Cox proportional hazards model was used to screen the risk factors of death. RESULTS: Only 9 children died with a median time of 6.3(2.6, 8.3) months among the 90 children with SAA after allo-HSCT. Among the 5 deaths due to infection, 3 were pulmonary infection, including 2 cases of cytomegalovirus pneumonia. One case developed septic shock due to gastrointestinal infection. One case experienced graft failure, which was complicated by bloodstream infection, and developed septic shock. Three cases died of transplantation-associated thrombotic microangiopathy (TA-TMA). One case died of gastrointestinal graft-versus-host disease (GVHD). The results of multivariate analysis showed that post-transplant +60 d PLT≤30×10⁹/L (HR=7.478, 95%CI : 1.177-47.527, P =0.033), aGVHD Ⅲ-Ⅳ (HR=7.991, 95%CI : 1.086-58.810, P =0.041), and TA-TMA occurrence (HR=13.699, 95%CI : 2.146-87.457, P =0.006) were independent risk factors for post-transplant mortality. CONCLUSION Allo-HSCT is an effective therapy for SAA in children. Post-transplant +60 d PLT≤30×10⁹/L, aGVHD Ⅲ-Ⅳ, and TA-TMA occurrence are independently associated with post-transplant mortality, which may be helpful for early detection of potential high-risk children and optimization of clinical diagnostic and treatment strategies.
Humans ; Anemia, Aplastic/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Risk Factors ; Retrospective Studies ; Child ; Transplantation, Homologous ; Male ; Female ; Graft vs Host Disease ; Child, Preschool ; Proportional Hazards Models ; Adolescent ; Infant

OBJECTIVE: To investigate the clinical features and risk factors associated with cutaneous chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: A retrospective analysis was conducted on the clinical data of children who underwent allo-HSCT in the Wuhan Children's Hospital from August 1, 2016, to December 31, 2023, and were regularly followed up for 1 year or more. The differences in clinical features between children with and without cutaneous cGVHD were compared, and the risk factors affecting the occurrence of cutaneous cGVHD were analyzed. RESULTS: During the study period, 296 children received allo-HSCT. Until December 31, 2024, follow-up showed that 20 children (6.8%) developed cutaneous cGVHD, which manifested as cutaneous lichenification, hyperpigmentation, keratosis pilaris, sclerotic changes, and hair or nail involvement. According to their skin lesion area and degree of grading, 5 cases were mild, 10 cases were moderate, and 5 cases were severe. Multivariate logistic regression analysis revealed that female donors and previous acute GVHD were risk factors for the development of cutaneous cGVHD after allo-HSCT. All 20 children were treated with glucocorticoid ± calcineurin inhibitors (tacrolimus/cyclosporine) as first-line therapeutic agents. Only 1 child improved after first-line treatment. The remaining 19 children treated with a second-line regimen of combination interventions based on individualized status, including 10 children who could not tolerate hormonotherapy or first-line treatment, and showed no significant improvement after 3 months, as well as 9 children with multi-organ cGVHD. After comprehensive second-line treatment, 17 children showed improvement in cutaneous symptoms. There were 3 deaths, including 1 due to primary disease recurrence and 2 due to pulmonary infections. CONCLUSION The skin is the first manifestation and most common organ involved in cGVHD in children. Cutaneous cGVHD severely affects the daily activities of transplanted children and requires prolonged immunosuppressive therapy, but has a favorable prognosis. First-line treatments for adults are not applicable to children who usually require a combination treatment with multiple drugs.
Humans ; Graft vs Host Disease/etiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Retrospective Studies ; Risk Factors ; Female ; Child ; Skin Diseases/etiology* ; Chronic Disease ; Transplantation, Homologous ; Male ; Child, Preschool ; Adolescent