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.

Objective To investigate the value of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid(Gd-EOB-DTPA)enhanced MRI and T1 mapping for evaluating vessels encapsulating tumor clusters(VETC)caused by hepatocellular carcinoma(HCC).Methods Totally 112 cases of HCC confirmed by surgical pathology were retrospectively enrolled and categorized into positive group(n=46)and negative group(n=66)based on the presence or absence of VETC.Gd-EOB-DTPA enhanced MRI features and T1 mapping parameters were compared between groups.Multivariate logistic regression analysis was used to identify independent risk factors for HCC VETC,and a combined nomogram model was developed.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the efficacy of the identified independent risk factors and nomogram model for predicting HCC VETC.Results The maximum diameter of HCC,incidence of non-smooth tumor margin,prevalence of peritumoral hypo-intensity on hepatobiliary phase(HBP),as well as T1 value of HBP(T1post)in positive group were all higher,while the change rate of T1 value(ΔT1％)in positive group was lower than those in negative group(all P＜0.05).The increased maximum diameter,non-smooth margin,peritumoral hypo-intensity on HBP and low ΔT1％were all independent risk factors for HCC VETC(all P＜0.05),with AUC for predicting HCC VETC of 0.680,0.675,0.686 and 0.752,respectively.The nomogram model developed based on the combination of the above factors showed sensitivity of 78.79％,specificity of 71.74％and AUC of 0.839 for predicting HCC VETC.Conclusion Gd-EOB-DTPA enhanced MRI combined with T1 mapping could be used to effectively predict HCC VETC.

Objective To examine the quality of Zukamu preparations through the national drug sampling and testing,and further understand their current quality status and existing problems.This work is benefit for improving the quality standard of Zukamu preparations and providing technical support for the drug regulatory authorities.Methods Samples of Zukamu preparations were collected from a total of 29 provinces in China,and were tested for description,identification,other requirements(weight variation,particle size,determination of water,disprsion,and microbial limit items),and assay in accordance with the national pharmaceutical standards.The test data were analyzed to evaluate the quality status of the Zukamu preparations,and exploratory research was carried out to address the problems found in the test.Results A total of 97 batches of Zukamu preparations were sampled,and the passing rate was 100.0%according to the current quality standard.Exploratory study,revealed that Zukamu preparation were subject to 4 testing standards,with uneven test items,missing items,poor operability,and lack of exclusivity in some items.The test based on the existing standards can't comprehensively evaluate the quality of the preparation.Conclusions Based on the national drug sampling and testing,combined with exploratory research on drug safety,authenticity and effectiveness,it is recommended to unify the quality standards of Zukamu preparations by combining with the work of standard improving,revising the identification method of thin-layer chromatography,increasing the content determination,and establishing the quick test method,thereby effectively evaluating and controling the quality of the samples of Zukamu preparations.

Objective:To compare the application of cloning sequencing and third-generation nanopore sequencing technology in the identification of raw materials mixed in Tibetan patent medicine Shiliujianwei powder,and to pro-vide a reference for the establishment of the specific identification method for the formulation of medicinal prepara-tions using the raw powder of medicinal herbs or herbal pieces.Methods:By investigating the different concentra-tions of ExTaq enzyme,genomic DNA,upstream and downstream primers in the PCR amplification system,the suit-able PCR amplification system of genomic DNA universal primers for self-made Tibetan medicine Shiliujianwei powder was determined.The amplified products of Shiliujianwei powder were sequenced by two methods,the first was cloned and sequenced by Sanger sequencing technology,and the second was sequenced by third generation nanopore sequen-cing technology.Results:The addition of ExTaq enzyme,upstream and downstream primers and genomic DNA in 20 μL PCR amplification system of Shiliujianwei powder and single medicinal samples were determined to be 0.4,1.5 and 1 μL,respectively.The amplification products of the DNA from self-made Shiliujianwei powder were cloned and sequenced by Sanger sequencing technology,then only the ITS2 sequence of Carthami flos was obtained.The amplified products of self-made pomegranate Jianwei powder DNA were sequenced by three-generation nanopore se-quencing technology,and the ITS2 sequences of Granati semen,Carthami flos,Piperis longi fructus and Amomi fruc-tus rotundus were finally obtained,but the ITS2 sequence of cinnamomi cortex was not obtained.Conclusion:Both cloning sequencing and the third generation nanopore sequencing could solve the problem of overlapping peaks in the direct sanger sequencing for the universal primer amplification products of patent drugs.The third generation nano-pore sequencing was better than cloning sequencing in the sequencing of the universal primer amplification products of patent drugs,but there were still one raw material medicine that have not been detected.It is of certain reference val-ue for the molecular biological identification and DNA barcoding study of different raw materials in the patent medi-cine to establish the specific identification method of Tibetan patent medicine Shiliujianwei powder.

Objective:To investigate the relationships among coping styles,negative life events,meaning in life,and psychological resilience in adolescents.Methods:A total of 1 434 adolescents aged 13 to 17 years comple-ted online questionnaire survey.The Simplified Coping Style Questionnaire(SCSQ),Adolescent Self-Rating Life E-vents Checklist(ASLEC),Chinese Meaning in Life Questionnaire(C-MLQ),and Connor-Davidson resilience scale(CD-RISC)were used to assess coping styles,perceived impact of negative life events,experience and pursuit of meaning in life,and ability to cope with and adapt to adversity,respectively.Logistic regression was used to explore the associations among these variables.Results:A total of 723 students(50.4％)tended to adopt negative coping styles when facing adverse events.Positive coping styles were negatively associated with being in senior high school(OR=0.62,P＜0.05)and impact of life events(OR=0.97,P＜0.001),while positively associated with sense of meaning in life(OR=1.04,P＜0.001)and psychological resilience(OR=1.04,P＜0.001).Conclusion:Among adolescents,positive coping styles are inversely associated with impact of negative life events,and positively associ-ated with both the sense of life meaning and psychological resilience.

Objective:To investigate the relationships among coping styles,negative life events,meaning in life,and psychological resilience in adolescents.Methods:A total of 1 434 adolescents aged 13 to 17 years comple-ted online questionnaire survey.The Simplified Coping Style Questionnaire(SCSQ),Adolescent Self-Rating Life E-vents Checklist(ASLEC),Chinese Meaning in Life Questionnaire(C-MLQ),and Connor-Davidson resilience scale(CD-RISC)were used to assess coping styles,perceived impact of negative life events,experience and pursuit of meaning in life,and ability to cope with and adapt to adversity,respectively.Logistic regression was used to explore the associations among these variables.Results:A total of 723 students(50.4％)tended to adopt negative coping styles when facing adverse events.Positive coping styles were negatively associated with being in senior high school(OR=0.62,P＜0.05)and impact of life events(OR=0.97,P＜0.001),while positively associated with sense of meaning in life(OR=1.04,P＜0.001)and psychological resilience(OR=1.04,P＜0.001).Conclusion:Among adolescents,positive coping styles are inversely associated with impact of negative life events,and positively associ-ated with both the sense of life meaning and psychological resilience.

The invasive arterial blood pressure(ABP)monitoring technique is widely utilized in the management of critically ill patients,providing medical professionals with real-time,continuous,and dynamic blood pressure data that plays a crucial role in guiding patient treatment.However,current traditional methods for arterial catheter blood collection and zero setting and measurement technology for ABP and central venous pressure(CVP)present certain issues such as complex operation procedures,inaccurate zero setting,and the inability to simultaneously monitor both ABP and CVP.Additionally,these methods may increase the risk of bloodstream infection and occupational exposure.Therefore,the department of critical care medicine at Tianjin Medical University General Hospital has developed a vascular access convenient blood collection device which has been granted a National Utility Model Patent(patent number:ZL 202322581247.4).This device includes a connecting tube,a specimen collection structure,a blood suction structure,a multifunctional pressure measurement device with laser emission structure,a pressure measurement conversion structure,and an efficient vascular access blood collection device.By optimizing the blood collection procedure and simplifying the manometry process,this design reduces the risk of bloodstream infection for patients and minimizes occupational exposure for medical staff.The device ensures accurate zero point adjustment of pressure measurements while guaranteeing the authenticity and reliability of collected data.Additionally,it supports synchronous monitoring of ABP and CVP,thereby saving medical consumables and reducing workload for healthcare professionals.This simple yet safe and efficient device meets clinical requirements effectively and is highly recommended for widespread use.

Objective:To investigate and analyze the safety of empirical or experimental medication (EEM) for adult-onset Still disease (AOSD) before diagnosis.Methods:The AOSD inpatients admitted to the Second Hospital of Jilin University from January 1, 2019 to December 31, 2023 were collected through hospital information system, and those who were misdiagnosed on admission were screened out. The main clinical characteristics, laboratory tests, misdiagnosis situation, the use of EEM and their adverse drug reactions (ADR), and the potential drug-drug interactions in the misdiagnosed patients were analyzed by descriptive statistics.Results:During the set time period, a total of 49 patients with AOSD were admitted to the hospital, of which 16 (32.7%) were misdiagnosed with other diseases on admission. Among the 16 patients, 10 were male and 6 were female, with a median age of 53 years. The main clinical manifestations were fever (in 15 patients), arthralgia/arthritis (in 10 patients), lymphadenopathy (in 10 patients), rash (in 9 patients), pleural or pericardial effusion (in 6 patients), pneumonia (in 5 patients), splenomegaly (in 4 patients) and sore throat (in 4 patients). Abnormalities in laboratory tests included white blood cell count elevation (in 13 patients), platelets count elevation (in 8 patients), serum ferritin elevation (>500 μg/L, in 12 patients), and abnormal liver function (in 9 patients). The median time of treatment before admission was 5.5 months (11 days to 27.0 months), and the median time from admission to diagnosis of AOSD was 12 days. Before the diagnosis of AOSD, all patients received a long time of EEM, including antibiotics, traditional Chinese medicine preparations, liver-protection drugs, anti-allergic drugs and antiviral drugs in 15, 12, 11, 3 and 2 patients, respectively. Four patients experienced ADRs related to EEM, all of which were caused by antibiotics. There were potential interactions in the therapeutic drugs in 4 patients.Conclusion:The misdiagnosis rate of AOSD was high. Patients might had accepted multiple EEMs before the definite diagnosis, which posed risks of ADRs and drug interactions.