ObjectiveTo optimize and validate the optimal sequential alcohol-water extraction process of modified Banxia Xiexintang（MBXT） based on pharmacodynamic evaluation， combined with the G1-entropy weight method and Box-Behnken response surface methodology， and to systematically and comprehensively analyze the material basis of this formula， providing a scientific basis for its quality control and industrial production. MethodsRats were randomly divided into the normal group， model group， metformin group， and MBXT water extraction， water extraction and ethanol precipitation， sequential ethanol-water extraction groups. Except for the normal group， a polycystic ovary syndrome with insulin resistance（PCOS-IR） model was established in all rats via a high-fat diet combined with letrozole induction. Enzyme-linked immunosorbent assay（ELISA） biochemical assay kits and hematoxylin-eosin（HE） staining were used to compare sex hormone levels in serum and ovarian histopathology， thereby screening extraction process routes. Based on this， a comprehensive score was constructed using the G1-entropy weight method based on the transfer rates of index components（berberine hydrochloride and baicalin） and the dry extract rate. Box-Behnken response surface methodology was then utilized to optimize the extraction process parameters. Finally， the chemical constituents of the sample from the optimal process were qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS）. ResultsPharmacodynamic findings revealed that compared with the normal group， serum testosterone（T） and luteinizing hormone（LH） levels were significantly elevated in the model group， while estradiol（E₂） and follicle-stimulating hormone（FSH） levels were significantly decreased（P<0.01）， with polycystic changes observed in ovarian tissues. Compared with the model group， all treatment groups significantly reversed the changes in sex hormone levels， with the sequential ethanol-water extraction group showing the optimal effect in improving the aforementioned indicators and pathological morphology， followed by subsequent process optimization. The optimized process involved adding 12 times the amount of 70% ethanol for extracting twice， each lasting 120 min， and adding 12 times the amount of water for extracting thrice， each lasting 90 min. Validation test results showed that under optimal process conditions， the average transfer rates of berberine hydrochloride and baicalin were 76.05% and 93.38%， respectively. MS analysis identified a total of 377 compounds， including 112 flavonoids， 41 terpenoids， 28 organic acids， 22 coumarins， and 8 alkaloids， while elucidating the cleavage patterns of key components. ConclusionThe optimized sequential ethanol-water extraction process is stable and feasible， effectively preserving the material basis of MBXT for treating PCOS-IR. It further clarifies the main chemical composition of this formula， providing a scientific basis for the development and quality control of its preparations.

ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang（MBXT） on polycystic ovary syndrome with insulin resistance（PCOS-IR） rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected， and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， and metformin group（0.158 g·kg^-1）， with a normal group set up separately. After 14 days of administration， the estrous cycle was observed， ovarian morphology was examined by hematoxylin-eosin（HE） staining， and the levels of testosterone（T）， estradiol（E₂）， follicle-stimulating hormone（FSH）， and luteinizing hormone（LH） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS） and RNA-Seq technology， respectively， followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats， improve polycystic ovarian lesions， and normalize dysregulated serum hormone levels（T， LH， E₂， FS， P<0.05， P<0.01）. Metabolomic analysis revealed that compared with the model group， MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione， mainly involving pathways such as steroid hormone biosynthesis， glutathione metabolism， and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes， and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems， including glutathione metabolism， peroxisome function， and fatty acid metabolism， thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes［such as Ras-related C3 botulinum toxin substrate 2 gene（Rac2） and Fas ligand gene（Faslg）］ showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network， particularly by regulating MHC-mediated immune responses， inhibiting local ovarian ferroptosis， and enhancing steroid hormone synthesis pathways.

ObjectiveTo investigate the mechanism of modified Banxia Xiexintang（MBXT） in improving ovarian dysfunction in polycystic ovary syndrome with insulin resistance（PCOS-IR） rats by inhibiting ferroptosis through the adenosine monophosphate（AMP）-activated protein kinase（AMPK）/fatty acid synthase（FASN）/glutathione peroxidase 4（GPX4） signaling pathway. MethodsSeventy-six female SD rats were randomly divided into a normal group（n=13） and a modeling group（n=63）. The modeling group established a PCOS-IR model by intragastric administration of letrozole combined with a high-fat diet for 21 days. After successful modeling， these rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， metformin group（0.158 g·kg^-1）， and high-dose of MBXT combined with ferroptosis inducer Erastin group（15 mg·kg^-1）， with 10 rats in each group. After 14 days of intervention， ovarian pathological morphology was observed by hematoxylin-eosin（HE） staining， the mitochondrial ultrastructure of granulosa cells was observed by transmission electron microscopy（TEM）， ovarian reactive oxygen species（ROS） levels were detected by dihydroethidium（DHE） probe， biochemical methods were used to detect Fe²⁺， malondialdehyde（MDA）， glutathione（GSH） and other indicators in ovarian tissues， serum sex hormone and insulin levels were measured by enzyme-linked immunosorbent assay（ELISA）， and the protein expressions of AMPK， FASN， acyl-CoA synthetase long-chain family member 4（ACSL4）， GPX4， and solute carrier family 7 member 11（SLC7A11） in ovarian tissues were detected by Western blot. ResultsCompared with the normal group， the model group showed polycystic changes in the ovaries， with atrophy of mitochondria in granulosa cells and increased membrane density. Serum levels of testosterone（T）， luteinizing hormone（LH）， and insulin were significantly increased（P<0.01）. The levels of ROS， MDA， 4-hydroxynonenal（4-HNE）， and Fe²⁺ in ovarian tissues were significantly elevated（P<0.01）， while adenosine triphosphate（ATP）， GSH， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） levels were significantly decreased（P<0.01）. The phosphorylation levels of AMPK and acetyl-CoA carboxylase （ACC）， as well as the protein expressions of SLC7A11， GPX4， and ferroptosis suppressor protein 1（FSP1） were significantly downregulated（P<0.01）， whereas the expressions of FASN， ACSL4， and nuclear receptor coactivator 4（NCOA4） were significantly upregulated（P<0.01）. Compared with the model group， MBXT intervention at various doses improved the above pathological changes and biochemical indicators in a dose-dependent manner， with the high-dose group showing the most significant effect（P<0.01）. Compared with the MBXT high-dose group， the high-dose of MBXT combined with ferroptosis inducer Erastin group restored ovarian ferroptosis characteristics in rats， with increased ROS and lipid peroxidation products， and altered expressions of key proteins（P<0.05， P<0.01）. ConclusionMBXT can effectively improve ovarian function and metabolic disorders in PCOS-IR rats. Its mechanism may be related to activating the AMPK/ACC signaling pathway， downregulating FASN and ACSL4 to reduce lipid peroxidation substrates， and restoring glucose-6-phosphate dehydrogenase/phosphoglycerate dehydrogenase（G6PD/PHGDH） metabolic flux to enhance the GPX4/FSP1 antioxidant defense system， thereby inhibiting ferroptosis in ovarian granulosa cells.

Bow hunter's syndrome,also referred to as rotational vertebral artery occlusion syndrome,is a rare etiological factor of posterior circulation infarction.This article reported a case of a young male patient who experienced recurrent posterior circulation infarctions caused by bilateral bow hunter's syndrome.Carotid ultrasonography confirmed a marked reduction in blood flow velocity in both vertebral arteries during neck rotation.High-resolution MR angiography and CT angiography of the head and neck revealed dissection involving the V3 segment of the left vertebral artery.The findings suggested that bow hunter's syndrome may be associated with thrombus formation secondary to repetitive mechanical compression of the vertebral artery intima,which could potentially lead to arterial embolism and subsequent cerebral infarction.This paper presents the patient's diagnostic and therapeutic course and includes a review of relevant literature aimed to enhance clinical awareness and understanding of this uncommon condition.

Colorectal cancer is the third leading cause of cancer-related mortality worldwide.Hepatic resection is the standard treatment for colorectal cancer liver metastasis.Microwave ablation(MWA),as a minimally invasive therapeutic approach,offers an alternative treatment option for these patients.But the clinical efficacy of hepatic resection and MWA in treating colorectal cancer liver metastasis patients is still inconclusive.Literatures were retrieved on comparative studies about the treatment of colorectal cancer liver metastasis with hepatic resection and MWA from multiple databases,including sinoMed,PubMed,Web of Science,EMBASE,CNKI,Wanfang,etc.The cutoffdate of retrieval was September 2024.Finally,a total of 13 studies comprising 2 057 patients,were included in this study.The papers were assessed using the Newcastle-Ottawa Scale and Jadad Scale.All included studies were of high quality.Data extraction focused on postoperative complications,length of hospital stay,surgical duration,hospitalization costs,and patient survival outcomes,including overall survival(OS)and disease-free survival(DFS).A meta-analysis was performed using Review Manager 5.4 software.There were no significant differences in OS(HR=1.03,95%CI:0.85-1.25,P=0.77)and DFS(HR=1.27,95%CI:0.94-1.71,P=0.13)between the MWA group and the hepatic resection group.In the subgroup analysis of patients with≤5 liver metastases and size of metastases≤3 cm,there were no statistically significant differences in OS and DFS between the MWA group and the hepatic resection group.The MWA group exhibited shorter hospital stay,reduced hospitalization costs,decreased surgical duration,less intraoperative blood loss,and lower incidence of complications compared to the hepatic resection group(P＜0.05).Therefore,for patients with colorectal liver metastases characterized by a number of liver metastases≤5 and size of metastases≤3 cm,MWA serves as an effective alternative to hepatic resection,with a lower morbidity associated with treatment.Further validation of these findings is warranted through additional randomized controlled trials and cohort studies.The registration number of this Meta-analysis on the PROSPERO platform is CRD42024610278.

Purpose To explore the clinicopathological features and potential clinical value of marginal zone lym-phoma(MZL)derived from T-bet positive memory B cell.Methods Clinical data of 67 cases of MZL were collected.Hematoxylin-eosin,immunohistochemistry,and multiple immunofluorescence stains,B cell receptor high throughput sequencing technology were used to study the histology,immunophenotype,and immunoglobulin heavy chain variable gene(IGHV)repertoire.Results T-bet was expressed in some MZL patients(34/67,50.75％),which was correla-ted with clinicopathological characteristics such as gender,clinical stage,and Ki67 proliferation index(P＜0.05),and also the progression-free survival was poor(P=0.012 2).T-bet positivity was a risk factor affecting the progres-sion of MZL.Microscopically,T-bet positive MZL frequently presented T-bet positive tumor B cells surrounded follicu-lar germinal center,"MALT ball"-type lymphoepithelial lesions,and IgG positive neoplastic plasma cells(P＜0.05).T-bet had no biased influence on the VH gene usage(P＞0.05).The common VH families were IGHV4 and IGHV3,and the segments were IGHV4-34 and IGHV3-30.The positivity of T-bet was associated with somatic hypermutation(SHM)state(P=0.014 9).The SHM was mainly in the range of 2％-4.9％in T-bet positive MZL,while in T-bet negative MZL the SHM was mostly greater than 5％.The VH gene usage was not correlated with the clinicopathological features of patients(P＞0.05).IGHV4 was correlated with progression-free survival in T-bet positive MZL(P=0.038 2).Conclusion The expression of T-bet in MZL is closely related to the clinicopathological features such as histology,plasma cell immunophenotype and IGHV gene repertoire,and the prognosis of patients is poor,which may be a potential molecular marker affecting the progression of MZL.

This paper analyzes the treatment process of a patient who developed severe acute respiratory distress syndrome (ARDS) following a chemical leak of dimethyl sulfate caused by factory operational error in February 2023, and explores the efficacy of extracorporeal membrane oxygenation (ECMO) in patient management. The patient developed severe respiratory symptoms five hours after chemical exposure and received sequential treatment with nasal high-flow oxygen therapy and invasive mechanical ventilation upon admission. When the oxygenation index dropped below 100 mmHg, veno-venous (VV) ECMO was initiated alongside 12-hour daily prone position ventilation to improve oxygenation and lung compliance. The patient recovered and was discharged following treatment. For patients with dimethyl sulfate poisoning complicated by severe ARDS, early implementation of VV-ECMO significantly improves treatment outcomes and prognosis.

Purpose To explore the clinicopathological features and potential clinical value of marginal zone lym-phoma(MZL)derived from T-bet positive memory B cell.Methods Clinical data of 67 cases of MZL were collected.Hematoxylin-eosin,immunohistochemistry,and multiple immunofluorescence stains,B cell receptor high throughput sequencing technology were used to study the histology,immunophenotype,and immunoglobulin heavy chain variable gene(IGHV)repertoire.Results T-bet was expressed in some MZL patients(34/67,50.75％),which was correla-ted with clinicopathological characteristics such as gender,clinical stage,and Ki67 proliferation index(P＜0.05),and also the progression-free survival was poor(P=0.012 2).T-bet positivity was a risk factor affecting the progres-sion of MZL.Microscopically,T-bet positive MZL frequently presented T-bet positive tumor B cells surrounded follicu-lar germinal center,"MALT ball"-type lymphoepithelial lesions,and IgG positive neoplastic plasma cells(P＜0.05).T-bet had no biased influence on the VH gene usage(P＞0.05).The common VH families were IGHV4 and IGHV3,and the segments were IGHV4-34 and IGHV3-30.The positivity of T-bet was associated with somatic hypermutation(SHM)state(P=0.014 9).The SHM was mainly in the range of 2％-4.9％in T-bet positive MZL,while in T-bet negative MZL the SHM was mostly greater than 5％.The VH gene usage was not correlated with the clinicopathological features of patients(P＞0.05).IGHV4 was correlated with progression-free survival in T-bet positive MZL(P=0.038 2).Conclusion The expression of T-bet in MZL is closely related to the clinicopathological features such as histology,plasma cell immunophenotype and IGHV gene repertoire,and the prognosis of patients is poor,which may be a potential molecular marker affecting the progression of MZL.

Objective:To investigate the characteristics and clinical effects of laparoscopic pneumovesical Cohen and laparoscopic Lich-Gregoir ureteral replantations for the treatment of primary obstructive megaloureter (POM) in children.Methods:A randomized controlled study was conducted.The clinical data of 51 children with unilateral POM admitted to the First Affiliated Hospital of Zhengzhou University from October 2018 to October 2023 were collected.Random number table method was used in the selection of surgical methods.They were divided into the laparoscopic pneumovesical Cohen ureteral replantation group (group A, 22 cases) and the laparoscopic Lich-Gregoir ureteral replantation group (group B, 29 cases) according to the surgical method.The anterior-posterior diameter(APD), maximum ureteral diameter and differential renal function parameters on the affected side were measured by color Doppler ultrasound of the urinary system, and compared between and within the two groups before and after surgery.The operation time, blood loss and postoperative intubation time were compared between the two groups.The incidence of postoperative complications such as reflux, bladder spasm, urinary retention and urinary tract infection was recorded.The independent and paired sample t-tests were used for statistical analysis. Results:The operation time and hematuria duration of group B [(125.7±14.2) min, (1.5±0.6) d] were significantly shorter than those of group A [(142.6±14.7) min, (2.8±0.7) d] (all P<0.05). The APD, maximum ureteral diameter, and differential renal function on the affected side of group A were (21.7±7.9) mm, (11.6±3.2) mm, and (28.2±4.9)% before surgery, and (10.3±4.5) mm, (6.0±2.0) mm and (43.8±4.4)% after surgery, respectively.The APD, maximum ureteral diameter, and differential renal function on the affected side of group B were (21.1±5.6) mm, (11.3±4.6) mm, and (30.2±5.5)% before surgery, and (10.2±4.5) mm, (6.6±2.0) mm, and (42.4±5.2)% after surgery, respectively.There was no statistically significant difference in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the two groups of children (all P>0.05). However, there were statistically significant differences in the values of APD, maximum ureteral diameter, and differential renal function before and after surgery between the same group of children (all P<0.01). No significant difference was found in intraoperative blood loss, postoperative intubation time, and postoperative complications between the two groups (all P>0.05). Conclusions:Both surgical methods are effective in the treatment of POM in children.Laparoscopic Lich-Gregoir ureteral replantation has advantages of less operation time compared with laparoscopic pneumovesical Cohen ureteral replantation.

Objective:To conduct a systematic review of risk prediction models for enteral feeding intolerance in ICU patients.Methods:Relevant literature was searched in China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc, VIP, PubMed, Web of Science, Cochrane Library, Embase, CINAHL, and Scopus, with search limits from the establishment of the databases up to July 24, 2024. Two researchers independently screened the literature and extracted data, using Prediction model Risk Of Bias ASsessment Tool to evaluate the quality of the included studies.Results:A total of 12 studies were included, which included 20 prediction models. The area under the receiver operating characteristic curve or C-index for these models ranged from 0.70 to 0.94. The overall bias risk of the 12 studies was high, with three studies having good applicability. The bias risk primarily stemmed from issues such as measurement of prediction factors, variable handling, sample size, outcome definition, and model performance evaluation.Conclusions:Existing risk prediction models for enteral feeding intolerance in ICU patients exhibit a high risk of bias. Further validation, optimization, or development of new models is required in the future.