Subacute cholecystitis complicated by gallbladder perforation often manifests as inflammatory lesions around the gallbladder， and it is extremely rare for this condition to cause massive hemorrhage into the omental bursa with secondary infection and result in massive hemorrhagic abscess. This article reports a case of a female patient， aged 68 years， who experienced massive hemorrhagic abscess in the omental bursa due to localized perforation and bleeding caused by a stone impacted in the gallbladder neck. The patient had a history of gallstones for 30 years and was admitted to Tianjin Nankai Hospital， Tianjin Medical University， after tertiary referral due to aggravated abdominal pain， chills， and fever. After comprehensive assessment by a multidisciplinary team， the patient underwent emergency laparoscopic cholecystectomy and clearance of the hemorrhagic abscess in the omental bursa. The patient recovered well and was discharged on day 10 after surgery， with good conditions during follow-up.

OBJECTIVE To evaluate the efficacy and safety of cholesterol absorption inhibitors （ezetimibe and hybutimibe） combined with statins for the treatment of dyslipidemia. METHODS Randomized controlled trials （RCTs） about above-mentioned drug combination in patients with dyslipidemia were retrieved from CNKI，PubMed and other Chinese and English databases. The retrieval time limit was from the establishment of the database to October 2025. After screening the literature，extracting the data，and evaluating the quality of the literature，network meta-analysis was performed using R software. RESULTS A total of 36 RCTs were included. Results showed that in reducing low-density lipoprotein cholesterol （LDL-C） and total cholesterol （TC）， ezetimibe+statins and hybutimibe+statins were significantly superior to statins+placebo and placebo alone （ P ＜0.05）. The top two interventions according to surface under the cumulative ranking curve （SUCRA） rankings were both ezetimibe+statins and hybutimibe+statins. In terms of triglyceride （TG） lowering， both hybutimibe+statins and ezetimibe+statins were significantly better than statins alone， statins+placebo and placebo alone （ P ＜0.05）， with hybutimibe+statins and ezetimibe+statins ranking top two by SUCRA. For apolipoprotein B （ApoB） reduction， ezetimibe+statins was significantly superior to statins alone and placebo alone （ P ＜0.05）， and the top two SUCRA rankings were ezetim ibe+statins and statins+placebo. In terms of high-density lipoprotein cholesterol （HDL-C） increase， placebo was significantly better than statins alone， hybutimibe+statins， statins+placebo， and ezetimibe+statins （ P ＜0.05）， and the top two SUCRA rankings were placebo alone and statins alone.There was no statistically significant difference in the overall incidence of adverse reactions among the interventions （ P ＞0.05）. CONCLUSIONS Ezetimibe combined with statins shows significant advantages in reducing LDL-C， TC and ApoB， while the hybutimibe combined with statins may have potential advantages in lowering TG； both combination regimens have good safety.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To investigate the role of serotonergic (5-HT) neurons activation in the dorsal raphe nucleus (DRN) in heat-induced seizures and its influence on breathing patterns in Scn1a + /- mice. Methods:24-day-old male Scn1a + /- mice were used for experiments, and sudden unexpected death in epilepsy(SUDEP) model was established through heat induction for 5 consecutive days. (1) Fluoxetine intervention experiment: 20 male mice were randomly divided into model group( n=10) and fluoxetine group ( n=10) according the weight-matched method. The fluoxetine group received intraperitoneal injection of fluoxetine (10 mg/kg) 45 min before heat induction each day for 5 consecutive days, while the model group received equal volume of 0.9% NaCl solution. (2) Chemogenetic activation experiment: 20 male mice were randomly divided into vector control group( n=10) and chemogenetic activation group ( n=10) according the weight-matched method. Empty vector or rAAV-TPH2-hM3d(Gq)-EGFP-WPREs was stereotaxically injected into DRN 14 d prior to seizure induction, and deschloroclozapine (5 mg/kg) was intraperitoneally injected 30 min before heat induction. Seizure characteristics and survival were assessed through video monitoring, and respiratory parameters were monitored. Immunofluorescence was used to detect colocalization of tryptophan hydroxylase 2(TPH2) and c-Fos in DRN. Statistical analysis was performed using SPSS 24.0 and GraphPad Prism 9.0. The independent sample t-test or Mann-Whitney test was used for inter-group comparison. Results:(1) In the fluoxetine intervention experiment: the survival rates between the model group and fluoxetine group showed no statistically significant difference ( χ2=2.23, P>0.05). As for the frequency of grade Ⅳ seizures, the model group (1.50(1.25, 2.35)min) demonstrated higher frequency than the fluoxetine group (0.43(0.20, 0.67)min) ( t=-3.40, P<0.05).With respect to respiratory parameters, the model group demonstrated shorter expiratory time ((0.10±0.02) s) and inspiratory time ((0.15±0.02) s) compared to the fluoxetine group ((0.16±0.05) s, (0.19±0.04) s) ( t=-3.47, -3.73, both P<0.01). The respiratory rate in the model group ((269.96±44.84) times/min) was significantly higher compared to the fluoxetine group ((195.04±52.37) times/min) ( t=3.44, P<0.01). The tidal volume in the model group ((0.10±0.02) mL) was significantly lower than the fluoxetine group ((0.13±0.04) mL) ( t=-2.19, P<0.05).The number of TPH2+ /c-Fos+ co-expressing cells in the model group (11.00±4.00) was lower than that in the fluoxetine group (33.00±8.39)( t=-4.16, P<0.05). (2) In the chemogenetic activation experiment: compared to the vehicle group, the chemogenetic activation group demonstrated significantly enhanced survival rates ( χ2=5.83, P<0.05). As for the frequency of grade Ⅴ seizures, the vehicle group (2.11(1.62, 3.44) times/min) showed higher frequency compared to the chemogenetic activation group (0.81(0.00, 1.62) times/min) ( t=18.00, P<0.05). In terms of respiratory parameters, the vehicle group showed shorter expiratory time ((0.10±0.01) s) and inspiratory time ((0.14±0.01) s) compared to the chemogenetic activation group ((0.12±0.01) s, (0.15±0.01) s) ( t=-2.78, -2.50, both P<0.05). The respiratory rate in the vehicle group ((208.37±9.73) times/min) was significantly higher than the chemogenetic activation group ((191.85±8.83) times/min) ( t=3.98, P<0.01). The tidal volume in the vehicle group ((0.09±0.01) mL) was significantly lower than the chemogenetic activation group ((0.12±0.02) mL) ( t=-4.77, P<0.001).The number of TPH2+ /c-Fos+ co-expressing cells in the vehicle group (9.00±3.46) was lower than that in the chemogenetic activation group (43.00±11.02)( t=-5.20, P<0.01). Conclusion:Specific activation of serotonergic neurons in the DRN can ameliorate heat-induced epileptic symptoms, improve respiratory function, and prolong survival time in Scn1a + /- mice.

Objective:To develop evaluation indicators for care ability of caregivers in home-based palliative care based on the Farran caregiver skills model.Methods:Based on the Farran caregiver skills model, a preliminary evaluation index system was constructed through theoretical analysis, literature review, and semi-structured interviews. From July to October 2024, experts in the field were selected to conduct expert consultations, revise and improve the index system, and determine the weight of the indicators through the analytic hierarchy process.Results:A total of two rounds of expert consultations were conducted. The effective response rates for the first and second rounds of expert consultation questionnaires were 90.00% (18/20) and 100.00% (18/18), respectively. In the two rounds of expert consultations, 15 experts (83.33%) and 3 experts (16.67%) respectively proposed revision suggestions. In the two rounds of consultation, the expert authority coefficients were 0.931 and 0.936, respectively, and the Kendall coefficient of concordance were 0.152~0.283、0.183~0.269 ( P<0.05). The final evaluation indicators for care ability of caregivers in home-based palliative care included four first-level indicators, 12 second-level indicators, and 45 third-level indicators. Conclusions:The evaluation indicators for care ability of caregivers in home-based palliative care developed are highly scientific and reliable, and can provide a reference for the evaluation of family caregiver care ability and the formulation of training programs.

Objective:To investigate the clinical value of continuous Bougie tube use in symmetrical three-port laparoscopic sleeve gastrectomy (LSG).Methods:The retrospective cohort study was conducted. The clinical data of 105 patients who underwent symmetrical three-port LSG at The First Hospital of Shanxi Medical University from October 2021 to October 2024 were collected. There were 57 males and 48 females, aged 27(range, 19-59)years. Of the 105 patients, 52 cases with continuous Bougie tube use during the surgery were divided into continuous group, while 53 cases with intermittent Bougie tube use were divided into intermittent group. Observation indicators: (1) surgical situations; (2) complications. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical situations. All 105 patients underwent symmetrical three-port LSG. The operation time was (57±4)minutes versus (76±4)minutes for the continuous group and the intermittent group, volume of intraoperative blood loss was (26±6)mL versus (59±9)mL, time to first out-of-bed activities was (218±8)minutes versus (299±9)minutes, time to first anal exhaust was (19.6±2.9)hours versus (25.8±2.8)hours, visual analogue scale score for pain at 6 hours postoperatively was 2.3±1.0 versus 4.7±1.0, and duration of postoperative hospital stay was (1.5±0.6)days versus (3.1±0.9)days for the two groups, respectively. There were significant differences in the above indicators between the two groups( t=26.92, 22.31, 48.91, 11.15, 13.25, 10.21, P<0.05). (2) Complications. No severe postopera-tive complication occurred in any of the 105 patients. There were 26 cases and 38 cases with nausea and vomiting at 2 hours postoperatively, showing a significant difference between them ( χ2=5.19, P<0.05). Conclusion:Compared to intermittent Bougie tube use, continuous Bougie tube use during symmetrical three-port LSG can significantly shorten operation time and duration of postoperative hospital stay, reduce intraoperative bleeding and postoperative pain, accelerate recovery of patients, and lower the incidence of complications.

Background and purpose:Epithelial ovarian cancer(EOC)has a poor prognosis and is prone to developing resistance to platinum-based chemotherapy.Exosomes are currently believed to be involved in platinum resistance in ovarian cancer.This study explored the role and mechanism of exosomes on platinum resistance of ovarian cancer.Methods:Through ultracentrifugation,exosomes were isolated and analyzed using electron microscopy,particle size studies,and Western blot for detailed exosome analysis.We detected the expression levels of exosomal proteins and related signaling pathways.Exosomal protein expression profile was analyzed by proteomics.Key differential proteins were screened by intersecting with existing drug resistance datasets.Furthermore,patients diagnosed with EOC via pathological analysis at the Fudan University Shanghai Cancer Center from August 2023 to August 2024,who underwent surgery and fulfilled the eligibility requirements,were gathered to examine the link between the expression of interferon-stimulated gene 15(ISG15)in serum exosomes and resistance to platinum medication.The expression levels of related proteins in serum exosomes were quantitatively detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic(ROC)curve was plotted to explore the predictive value of serum exosomal protein in ovarian cancer resistance.Results:Exosomes derived from platinum-sensitive and drug-resistant ovarian cancer cells were extracted and proteomic analysis was further performed.We identified 9 differential proteins associated with platinum-resistance and found the key molecule interferon-stimulated gene 15(ISG15).Compared with sensitive cells,the expression of ISG15 in exosomes of drug-resistant ovarian cancer cells was significantly upregulated.Exosome tracer tests showed that exosomes were successfully taken up by ovarian cancer receptor cells.After coculture with drug-resistant exosomes,the expression level of ISG15 in ovarian cancer receptor cells was increased.Knockdown ISG15 in EOC cells decreased the expression of ISG15 in exosomes,and incubation of ISG15-knockdown exosomes decreased the cell viability on the condition of platinum drugs,indicating that ISG15 in exosomes regulated platinum resistance of ovarian cancer cells.Moreover,ISG15 could regulate the expression of multidrug resistance protein 1(MDR1)through phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/nuclear factor-kappa-light-chain-enchancer of activated B cells(NF-κB)signaling pathway.This study included a total of 87 patients.Clinical serum samples also showed that the expression of ISG15 in exosomes was higher in platinum-resistant ovarian cancer patients than in sensitive ovarian cancer patients.Using serum exosomal ISG15 as an indicator to distinguish between sensitivity and resistance,the area under ROC curve was 0.779(P＜0.05),cutoffvalue was 27.35ng/mL,sensitivity was 70.2%,and specificity was 76.4%.Conclusion:ISG15 in exosomes can regulate the expression of MDR1 in ovarian cancer cells through PI3K/AKT/NF-κB signaling pathway,and promote platinum resistance in ovarian cancer cells.

Objective:To investigate the role of serotonergic (5-HT) neurons activation in the dorsal raphe nucleus (DRN) in heat-induced seizures and its influence on breathing patterns in Scn1a + /- mice. Methods:24-day-old male Scn1a + /- mice were used for experiments, and sudden unexpected death in epilepsy(SUDEP) model was established through heat induction for 5 consecutive days. (1) Fluoxetine intervention experiment: 20 male mice were randomly divided into model group( n=10) and fluoxetine group ( n=10) according the weight-matched method. The fluoxetine group received intraperitoneal injection of fluoxetine (10 mg/kg) 45 min before heat induction each day for 5 consecutive days, while the model group received equal volume of 0.9% NaCl solution. (2) Chemogenetic activation experiment: 20 male mice were randomly divided into vector control group( n=10) and chemogenetic activation group ( n=10) according the weight-matched method. Empty vector or rAAV-TPH2-hM3d(Gq)-EGFP-WPREs was stereotaxically injected into DRN 14 d prior to seizure induction, and deschloroclozapine (5 mg/kg) was intraperitoneally injected 30 min before heat induction. Seizure characteristics and survival were assessed through video monitoring, and respiratory parameters were monitored. Immunofluorescence was used to detect colocalization of tryptophan hydroxylase 2(TPH2) and c-Fos in DRN. Statistical analysis was performed using SPSS 24.0 and GraphPad Prism 9.0. The independent sample t-test or Mann-Whitney test was used for inter-group comparison. Results:(1) In the fluoxetine intervention experiment: the survival rates between the model group and fluoxetine group showed no statistically significant difference ( χ2=2.23, P>0.05). As for the frequency of grade Ⅳ seizures, the model group (1.50(1.25, 2.35)min) demonstrated higher frequency than the fluoxetine group (0.43(0.20, 0.67)min) ( t=-3.40, P<0.05).With respect to respiratory parameters, the model group demonstrated shorter expiratory time ((0.10±0.02) s) and inspiratory time ((0.15±0.02) s) compared to the fluoxetine group ((0.16±0.05) s, (0.19±0.04) s) ( t=-3.47, -3.73, both P<0.01). The respiratory rate in the model group ((269.96±44.84) times/min) was significantly higher compared to the fluoxetine group ((195.04±52.37) times/min) ( t=3.44, P<0.01). The tidal volume in the model group ((0.10±0.02) mL) was significantly lower than the fluoxetine group ((0.13±0.04) mL) ( t=-2.19, P<0.05).The number of TPH2+ /c-Fos+ co-expressing cells in the model group (11.00±4.00) was lower than that in the fluoxetine group (33.00±8.39)( t=-4.16, P<0.05). (2) In the chemogenetic activation experiment: compared to the vehicle group, the chemogenetic activation group demonstrated significantly enhanced survival rates ( χ2=5.83, P<0.05). As for the frequency of grade Ⅴ seizures, the vehicle group (2.11(1.62, 3.44) times/min) showed higher frequency compared to the chemogenetic activation group (0.81(0.00, 1.62) times/min) ( t=18.00, P<0.05). In terms of respiratory parameters, the vehicle group showed shorter expiratory time ((0.10±0.01) s) and inspiratory time ((0.14±0.01) s) compared to the chemogenetic activation group ((0.12±0.01) s, (0.15±0.01) s) ( t=-2.78, -2.50, both P<0.05). The respiratory rate in the vehicle group ((208.37±9.73) times/min) was significantly higher than the chemogenetic activation group ((191.85±8.83) times/min) ( t=3.98, P<0.01). The tidal volume in the vehicle group ((0.09±0.01) mL) was significantly lower than the chemogenetic activation group ((0.12±0.02) mL) ( t=-4.77, P<0.001).The number of TPH2+ /c-Fos+ co-expressing cells in the vehicle group (9.00±3.46) was lower than that in the chemogenetic activation group (43.00±11.02)( t=-5.20, P<0.01). Conclusion:Specific activation of serotonergic neurons in the DRN can ameliorate heat-induced epileptic symptoms, improve respiratory function, and prolong survival time in Scn1a + /- mice.

Objective:Using bacterial culture as the gold standard, to evaluate the agreement of rapid antigen detection test (RADT) and rapid nucleic acid test (RNAT) in diagnosing group A Streptococcus (GAS) pharyngitis in pediatric outpatients, and assess their potential clinical utility. Methods:This cross-sectional study prospectively collected throat swab specimens and clinical data of 338 children diagnosed with acute pharyngitis at the Department of Outpatient Beijing Children′s Hospital, Capital Medical University, between July 2023 and February 2024. The specimens were tested for GAS bacterial culture, RADT and RNAT. Using bacterial culture results as the reference standard, Kappa consistency analysis was performed to assess the diagnostic concordance between RADT and RNAT. Chi-square test was used to compare clinical characteristics between cases diagnosed by different methods.Results:In the 338 children diagnosed with pharyngitis, 195 were male and 143 were female, with an age at the visit of 7.4 (5.9, 7.4) years. The positivive rates for GAS detection were 25.7% (87/338) by bacterial culture, 20.7% (70/338) by RADT, and 41.7% (141/338) by RNAT. In terms of diagnostic performance, RADT exhibited a higher specificity (96.8% (243/251)) and better agreement with bacterial culture results ( κ=0.73), whereas RNAT showed greater sensitivity (95.4% (83/87)) but lower specificity (76.9% (193/251)) and moderate agreement ( κ=0.61). Among the 87 children with positive bacterial culture for GAS, 56 were male and 31 were female, with an age at visit of 7.3 (6.2, 8.8) years. Clinically, body temperature predominantly ranged from 38.1 to 39.0 ℃ in 48 cases (55.2%), and common accompanying symptoms included sore throat 62 cases (71.3%), cough 33 cases (37.9%), and cervical lymphadenopathy or tenderness 16 cases (18.4%). On physical examination, tonsillar enlargement was present in 73 cases (83.9%) and exudate in 37 cases (42.5%). The McIsaac score was most frequently 4 points, observed in 37 cases (42.5%). Laboratory tests showed a peripheral white blood cell (WBC) count of 14.5 (12.3, 18.7)×10?/L and C-reactive protein (CRP) concentration of 22.0 (10.1, 41.4) mg/L. There were no statistically significant differences in the proportion of fever, sore throat, cough, tender cervical lymphadenopathy, tonsillar exudates, or tonsillar enlargement, nor in WBC count or CRP, among children who tested positive by RADT, RNAT, or bacterial culture (all P>0.05). Conclusions:Compared with bacterial culture,the RADT demonstrates higher specificity, while the RNAT exhibits greater sensitivity. Both methods show good concordance with culture results and may serve as effective adjunctive tools for the early screening of GAS pharyngitis.