Objective To characterize Schistosoma japonicum Class F G protein-coupled receptors (GPCRs), and to decipher the biological function of S. japonicum Smoothened receptor (SjSMO), so as to provide insights into screening of novel anti-schistosomal drug targets. Methods Six Class F GPCRs were identified from the S. japonicum GPCR library using a hidden Markov model (HMM) and genome annotation filese, including five frizzled (FZD) receptors (SjFZD4, SjFZD5, SjFZD7, SjFZD8, SjFZD10) and one Smoothened receptor (SjSMO). Protein domain analysis was performed at the SMART website, and a phylogenetic tree was built with the software MEGA 11.0 and refined with the Interactive Tree Of Life (iTOL) tool. The expression profile and tissue localization of S. japonicum class F GPCRs were analyzed using the real-time fluorescence-based quantitative PCR (RT-qPCR) assay and in situ hybridization, and the effects of SjSMO on parasite growth, development, reproduction, and oviposition were examined using in vivo and in vitro RNA interference (RNAi). S. japonicum adult worms were selected for double-stranded RNAi (dsRNA) in in vitro experiments, and a green fluorescent protein (GFP) negative control group and SjFZD4, SjFZD5, SjFZD7, SjFZD8, SjFZD10, and SjSMO dsRNAi groups were assigned to observe the parasite vitality and state and calculate the female and male rating rate. For in-vivo animal experiments, 6-week-old SPF female mice of the Kunming strain were randomly divided into a GFP dsRNA negative control group and SjFZD4, SjFZD5, SjFZD7, SjFZD8, SjFZD10, and SjSMO dsRNAi groups. Worms and liver tissues were collected for measurement of the worm length and estimation of the worm burdens, and changes in the parasite reproductive organs were observed using alum carmine staining. In addition, the number of S. japonicum eggs in mouse livers was counted and the pathological damages of mouse livers were recorded. Results The five FZD receptors and one Smoothened receptor all contained a conserved Frizzled domain. Phylogenetic analysis revealed that SjSMO formed an independent evolutionary clade, which exhibited a far genetic distance from the FZD family. RT-qPCR assay quantified stable SjSMO expression in male worms but gradually decreased in female worms with worm development, and in situ hybridization revealed high systemic expression of SjSMO. In vitro RNAi results revealed a significant difference in pairing rates among all groups (χ² = 130.530, P < 0.000 1). Only the SjSMO interference group exhibited a markedly reduced worm pairing rate of 20.00%, which was significantly lower than that of the control group (94.74%) (P < 0.000 1), accompanied by decreased worm vitality. In contrast, no statistically significant differences in pairing rates were observed between each FZD family gene interference group and the control group (all P > 0.05). In vivo RNAi assay revealed that SjSMO dsRNAi 1 to 26 days post-infection resulted in a significant reduction in worm length, with reductions in the male worm length by 32.27% and female worm length by 36.77% as compared to controls [male worms: (6.51 ± 1.77) mm vs. (9.62 ± 1.44) mm, t = 7.196, P < 0.000 1; female worms: (5.49 ± 1.36) mm vs. (8.68 ± 2.60) mm, t = 5.953, P < 0.000 1], as well as arrest of testicular development in male worms and ovarian development in females. In addition, SjSMO dsRNAi 26 to 42 days post-infection was found to significantly reduce hepatic egg burdens in mice, with a 49.10% reduction in the count of liver eggs in the SjSMO dsRNAi group relative to the GFP dsRNA negative control group [(2 824 ± 844) eggs per gram vs. (5 548 ± 797) eggs per gram; t = 4.064, P < 0.05], and to alleviate granuloma formation and severity of hepatic fibrosis. Conclusion SjSMO is a key receptor that regulates the growth, development, reproduction, and oviposition of S. japonicum, which provides a new potential target for development of anti-schistosomal drugs.

Objective To investigate the effect of body position angle on gastric insufflation during the induction of general anesthesia in pediatric patients undergoing day surgery.Methods A total of 111 children scheduled for elective tracheal intubation under general anesthesia at the First Affiliated Hospital of Guangxi Medical University from December 2022 to March 2023 were selected as study subjects.Six children were ex-cluded due to unclear sonographic visualization of the gastric antrum,resulting in 105 children ultimately in-cluded in the study.The children were divided into three groups using a random number table method:Group D0(supine position),Group D5(5° head-up position),and Group D10(10° head-up position),with 35 children in each group.The presence of a"comet-tail artifact"on ultrasound was used as the criterion for determining gastric insufflation during anesthesia induction.The gastric antrum cross-sectional area(CSA)of the gastric antrum was measured before mask ventilation after loss of consciousness(T1)and immediately after tracheal intubation following mask ventilation(T2).The incidence of gastric insufflation,changes in CSA and their differences,and vital sign changes at T1 and T2,were compared among the three groups.Results Compared with Group D0,the incidence of gastric insufflation was significantly lower in Groups D5 and D10[25.7％(9/35)vs.20.0％(7/35)vs.54.0％(19/35)],and the difference was statistically significant(P＜0.05).Howev-er,there was no significant difference between Group D5 and Group D10(P＞0.05).No significant difference was observed in CSA at T1 among the three groups(P＞0.05).At T2,a statistically significant difference in CSA was found among the three groups(P＜0.05),with Group D10 showing a smaller CSA than Group D0(P＜0.05).The difference in CSA changes was statistically significant among the three groups(P＜0.05),with Groups D5 and D10 exhibiting smaller changes than Group D0,and Group D10 showing a smaller change than Group D5(P＜0.05).No significant differences were observed in mean artery pressure(MAP),heart rate,pulse oxygen saturation(SpO2)and pressure of end-tidal carbon dioxide(PETCO2)at T1 and T2 among the three groups(P＞0.05).A total of 6 children(5.7％)required brief adjustments in jaw support due to irregular PETCO2 waveforms or abnormal peak airway pressure.Conclusion In pediatric patients undergoing day sur-gery under general anesthesia,a 5° head-up position during induction significantly reduces the incidence of gas-tric insufflation and minimizes changes in gastric antral CSA,while a 10° head-up position does not provide ad-ditional benefits.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective:To evaluate the safety and effectiveness of fuzuloparib for the treatment of ovarian epithelial cancer patients in the real world setting.Methods:A retrospective analysis was conducted on the baseline data of 4 620 ovarian cancer patients who had received fuzuloparib monotherapy or combination therapy. Another 224 ovarian cancer patients who were willing to receive fuzuloparib monotherapy or combination therapy were prospectively enrolled, and their baseline characteristics, drug effectiveness, and safety data were analyzed.Results:(1) Among the 4 620 patients in the retrospective cohort, the median age of patients was 60 years; tumor types: 89.8% (4 149/4 620) had ovarian cancer. Among patients with clearly documented information, the vast majority had a histological type of serous carcinoma (82.9%, 3 770/4 546) and International Federation of Gynecology and Obstetrics (FIGO) staging of Ⅲ-Ⅳ (90.9%, 1 537/1 691). (2) Among the 224 patients in the prospective cohort, the median age of patients was 57 years; tumor types: 83.9% (188/224) had ovarian cancer. Among patients with clearly documented records, the predominant pathologic type was serous carcinoma (91.9%, 193/210), and FIGO stage was Ⅲ-Ⅳ in 79.9% (139/174). (3) Among the 224 prospective patients: 84 patients received first-line fluzoparib maintenance therapy, 92 patients received fluzoparib maintenance therapy after platinum-sensitive recurrence, 23 patients received direct fluzoparib treatment after platinum-sensitive recurrence, 19 patients received direct fluzoparib treatment after platinum-resistant recurrence. The median follow-up durations were 8.5, 8.7, 7.9, and 6.7 months, respectively. The median durations of fluzoparib treatment were 6.7, 4.8, 3.1, and 1.9 months, respectively. The median progression-free survival (PFS) times were not reached during follow-up, 12.6 months, not reached during follow-up, and 4.8 months, respectively. The 1-year PFS rates were 84.1%, 55.0%, 69.8%, and 45.5%, respectively. The remaining 6 patients received other fluzoparib regimens. (4) Among the 224 patients in the prospective dataset, 205 had safety data recorded. Of these, 127 patients (62.0%, 127/205) experienced treatment-related adverse events, with common events including anemia (24.4%, 50/205), thrombocytopenia (21.0%, 43/205), and leukopenia (19.5%, 40/205). Among the 205 patients, 43 (21.0%, 43/205) experienced grade 3 or higher treatment-related adverse events, with common events including anemia (8.3%, 17/205) and thrombocytopenia (8.3%, 17/205).Conclusions:The effectiveness of fuzuloparib in clinical application is generally consistent with other drugs in the same class, with good safety. This study provids new clinical evidence for the treatment of ovarian cancer with fuzuloparib.

Objective To investigate the effect of electroacupuncture(EA)on the behaviors of lipopolysaccharide(LPS)-induced depression-like mice and explore the potential molecular mechanism of the antidepressant effect of EA using transcriptomics sequencing technology.Methods Thirty-six male specific pathogen-free-grade C57BL/6J mice were divided into the normal,the model,and the EA groups using the random number table method,with 12 mice per group.The EA group received a daily 20-minute EA at the"Baihui"and"Yintang"acupoints for 7 days.After 7 days of EA treatment,1.5 mg/kg LPS was injected intraperitoneally into the model and EA groups,whereas the normal group received an injection of an equal volume of saline solution.Depressive behaviors were assessed using the open-field test,tail-suspension test,and other relevant tests.Pathologic morphology of the hippocampus tissue was determined using hematoxylin-eosin staining.Transcriptomics technology was used to identify differentially expressed genes in the hippocampus,and bioinformatics analysis was performed.Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of hematopoietic cell kinase(Hck),adhesion G protein-coupled receptor E1(Adgre1),Toll-like receptor 2(Tlr2),and Gm49037 in the hippocampus.Results Compared to the normal group,mice in the model group exhibited a decrease in total travel distance,central travel distance,center area time(P＜0.01),as well as an increase in tail-suspension immobility time(P＜0.05).Hippocampal neurons were loosely arranged,and some neurons had blurred boundaries.Compared to the model group,mice in the EA group showed an increase in open-field total travel distance,central travel distance,center area time(P＜0.05),as well as a decrease in tail-suspension immobility time(P＜0.01);Additionally,hippocampal neurons were more tightly arranged,exhibiting clearer morphology and structure.Transcriptomic analysis revealed that 779 differentially expressed genes were identified in the model group compared to the normal group,whereas 172 genes differed between the EA and model groups.Nineteen genes were upregulated in the model group but downregulated in the EA group,and ten genes were down-regulated in the model group but up-regulated in the EA group.Gene Ontology Functional Analysis indicated that these genes primarily function in immune responses,Toll-like receptor activity,cell surface receptor signaling pathways,and interleukin-10 production.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment in inflammation-related pathways,including Toll-like receptor signaling pathway and tumor necrosis factor signaling pathway.Compared to the normal group,Hck,Adgre1,and Tlr2 mRNA expressions were elevated in the model group(P＜0.01),whereas there was a decrease tendency for Gm49037 mRNA expression and there was no significant difference(P＞0.05);compared to the model group,Hck,Adgre1,and Tlr2 mRNA expressions were decreased in the EA group(P＜0.05),whereas there was an increase tendency for Gm49037 mRNA expression and there was no significant difference(P＞0.05).Conclusion EA alleviated depressive-like behavior and pathological damage in the hippocampus in LPS-induced mice,which may be related to attenuating hippocampal inflammatory pathways,and Hck,Adgre1,and Tlr2 genes may be the potential targets for its effect.

Objective To investigate the effect of electroacupuncture(EA)on the behaviors of lipopolysaccharide(LPS)-induced depression-like mice and explore the potential molecular mechanism of the antidepressant effect of EA using transcriptomics sequencing technology.Methods Thirty-six male specific pathogen-free-grade C57BL/6J mice were divided into the normal,the model,and the EA groups using the random number table method,with 12 mice per group.The EA group received a daily 20-minute EA at the"Baihui"and"Yintang"acupoints for 7 days.After 7 days of EA treatment,1.5 mg/kg LPS was injected intraperitoneally into the model and EA groups,whereas the normal group received an injection of an equal volume of saline solution.Depressive behaviors were assessed using the open-field test,tail-suspension test,and other relevant tests.Pathologic morphology of the hippocampus tissue was determined using hematoxylin-eosin staining.Transcriptomics technology was used to identify differentially expressed genes in the hippocampus,and bioinformatics analysis was performed.Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of hematopoietic cell kinase(Hck),adhesion G protein-coupled receptor E1(Adgre1),Toll-like receptor 2(Tlr2),and Gm49037 in the hippocampus.Results Compared to the normal group,mice in the model group exhibited a decrease in total travel distance,central travel distance,center area time(P＜0.01),as well as an increase in tail-suspension immobility time(P＜0.05).Hippocampal neurons were loosely arranged,and some neurons had blurred boundaries.Compared to the model group,mice in the EA group showed an increase in open-field total travel distance,central travel distance,center area time(P＜0.05),as well as a decrease in tail-suspension immobility time(P＜0.01);Additionally,hippocampal neurons were more tightly arranged,exhibiting clearer morphology and structure.Transcriptomic analysis revealed that 779 differentially expressed genes were identified in the model group compared to the normal group,whereas 172 genes differed between the EA and model groups.Nineteen genes were upregulated in the model group but downregulated in the EA group,and ten genes were down-regulated in the model group but up-regulated in the EA group.Gene Ontology Functional Analysis indicated that these genes primarily function in immune responses,Toll-like receptor activity,cell surface receptor signaling pathways,and interleukin-10 production.Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed enrichment in inflammation-related pathways,including Toll-like receptor signaling pathway and tumor necrosis factor signaling pathway.Compared to the normal group,Hck,Adgre1,and Tlr2 mRNA expressions were elevated in the model group(P＜0.01),whereas there was a decrease tendency for Gm49037 mRNA expression and there was no significant difference(P＞0.05);compared to the model group,Hck,Adgre1,and Tlr2 mRNA expressions were decreased in the EA group(P＜0.05),whereas there was an increase tendency for Gm49037 mRNA expression and there was no significant difference(P＞0.05).Conclusion EA alleviated depressive-like behavior and pathological damage in the hippocampus in LPS-induced mice,which may be related to attenuating hippocampal inflammatory pathways,and Hck,Adgre1,and Tlr2 genes may be the potential targets for its effect.

Objective To analyze the evaluation value of whole brain computed tomography perfusion imaging(CTPI)scanning parameters on collateral circulation in ischemic stroke.Methods One hundred and two patients with ischemic stroke were selected,according to the condition they were divided into mild group(n=26),moderate group(n=56),and severe group(n=20).The col-lateral circulation status was evaluated based on the modified American Society of Interventional and Therapeutic Neuroradiology(ASITN)/Society of Interventional Radiology(SIR)score of dynamic CT angiography,and was divided into good group(n=61)and poor group(n=41).CTPI parameters were compared between different groups of patients with cerebral blood flow(CBF),cerebral blood volume(CBV),mean transit time(MTT),and time to peak(TTP).Results The CBF and CBV in the severe group were lower than those in the mild and moderate groups,while the MTT and TTP were higher than those in the mild and moderate groups(P<0.05);The CBF and CBV in the moderate group were lower than those in the mild group,while the MTT and TTP were higher than those in the mild group(P<0.05).The CBF and CBV in the good group were higher than those in the poor group,while the MTT and TTP were lower than those in the poor group(P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity of CBF,CBV,MTT,and TTP in predicting poor collateral circulation was 0.820,0.672,0.803,and 0.820,respectively;The specificity was 0.854,0.756,0.732,and 0.780,respectively.Conclusion CTPI scanning parameters have certain values to assess the intracranial collateral circulation status in patients with ischemic stroke.

BACKGROUND: Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited. METHODS: This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed. RESULTS: Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]-3rd quartile [Q3]: 11-44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P  = 0.021) and transitioning to plaque psoriasis ( P  = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1-Q3: 2-41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1-Q3: 13.0-23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. CONCLUSIONS The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.
Humans ; Male ; Female ; Psoriasis/pathology* ; Adult ; Cross-Sectional Studies ; Adolescent ; Child ; Young Adult ; Quality of Life ; Middle Aged ; China/epidemiology* ; Recurrence ; Risk Factors ; Surveys and Questionnaires ; East Asian People

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

Objective To analyze the evaluation value of whole brain computed tomography perfusion imaging(CTPI)scanning parameters on collateral circulation in ischemic stroke.Methods One hundred and two patients with ischemic stroke were selected,according to the condition they were divided into mild group(n=26),moderate group(n=56),and severe group(n=20).The col-lateral circulation status was evaluated based on the modified American Society of Interventional and Therapeutic Neuroradiology(ASITN)/Society of Interventional Radiology(SIR)score of dynamic CT angiography,and was divided into good group(n=61)and poor group(n=41).CTPI parameters were compared between different groups of patients with cerebral blood flow(CBF),cerebral blood volume(CBV),mean transit time(MTT),and time to peak(TTP).Results The CBF and CBV in the severe group were lower than those in the mild and moderate groups,while the MTT and TTP were higher than those in the mild and moderate groups(P<0.05);The CBF and CBV in the moderate group were lower than those in the mild group,while the MTT and TTP were higher than those in the mild group(P<0.05).The CBF and CBV in the good group were higher than those in the poor group,while the MTT and TTP were lower than those in the poor group(P<0.05).Receiver operating characteristic(ROC)curve analysis showed that the sensitivity of CBF,CBV,MTT,and TTP in predicting poor collateral circulation was 0.820,0.672,0.803,and 0.820,respectively;The specificity was 0.854,0.756,0.732,and 0.780,respectively.Conclusion CTPI scanning parameters have certain values to assess the intracranial collateral circulation status in patients with ischemic stroke.