OBJECTIVE To ensure the safety of patients’ drug use and control the risk of medical insurance expenditure by upgrading the pre-prescription review system to conduct pre-review on prescriptions from internet hospitals and external prescriptions， as well as to review the payment methods of drugs （including in-hospital and external drug dispensing）. METHODS The data interfaces of prescriptions from internet hospitals and external prescriptions were integrated to achieve real-time rational drug use intervention. Additionally， an intelligent review project for payment method was added to precisely intervene in the medical insurance payment methods of drugs. The effect of the system upgrade was evaluated by comparing the qualification rates of prescriptions from internet hospitals and external prescriptions and the suspected amounts of drug violations from January to April 2025 （before the system upgrade） and May to August 2025 （after the system upgrade）. RESULTS After the upgrade of the pre-prescription review system， the qualification rates of prescriptions from internet hospitals and external prescriptions increased by 3.5% [95% confidence interval （CI）＝0.3%-6.7%， P ＝0.037 ] ； the suspected amounts of drug violations decreased to 52.9% of the pre-upgrade level （95%CI＝31.6%-88.5%， P ＝0.026）， and the average monthly sequential decrease was 29.5% （95%CI＝12.2%-43.4%， P ＝0.012）. Moreover， the addition of the intelligent review project for payment methods promoted the management of off-label drug use in our hospital. After the upgrade， a total of 79 filling valid applications for off-label drug use were received and archived. CONCLUSIONS The upgrade of the pre-prescription review system effectively improves the review qualification rates of prescriptions from internet hospitals and external prescriptions and the accuracy of medical insurance payment for drugs， and strengthens the supervision of off-label drug use， achieving dual guarantees of clinical rationality and medical insurance compliance.

ObjectiveTo investigate the effect of Niuhuang Qingxinwan （NHQXW） in improving intracerebral hemorrhage （ICH） with Tanre Fushi （phlegm-heat and fu-organ excess） syndrome by maintaining blood-brain barrier （BBB） integrity， and to explore its potential mechanism. MethodsMale mice were administered with 15% autologous feces for 3 consecutive days to simulate spontaneous Tanre Fushi syndrome， followed by surgical induction of collagenase-induced ICH on the fourth day. Mice were randomly assigned to seven groups： Sham， Sham+NHQXW-H， collagenase， collagenase+feces， and NHQXW intervention groups at low （NHQXW-L， 0.225 g·kg^-1）， medium （NHQXW-M， 0.45 g·kg^-1）， and high （NHQXW-H， 0.9 g·kg^-1） doses. Treatments were administered for 3 days after surgery. NHQXW effects on Tanre Fushi syndrome were assessed via fecal water content and small intestinal carbon propulsion rate. Protective effects of NHQXW against ICH with Tanre Fushi syndrome were evaluated by measuring hematoma volume， neurological deficits， and brain water content. BBB integrity was further assessed using Evans blue staining， hematoxylin-eosin （HE） staining， immunofluorescence， and Western blot for Claudin-5， plasmalemma vesicle-associated protein （PLVAP）， matrix metalloproteinase （MMP）-2， and MMP-9. The potential mechanism of NHQXW was investigated by detecting protein expression of protein kinase B （Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， signal transducer and activator of transcription 3 （STAT3）， Yes-associated protein （YAP）， and their phosphorylated forms. ResultsCompared with the collagenase+feces group， NHQXW-M and NHQXW-H significantly reduced fecal water content （P<0.05， P<0.01） and intestinal propulsion rate （P<0.01）， alleviated neurological deficits （P<0.01）， decreased hematoma volume （P<0.01） and Evans blue extravasation （P<0.01）， increased Claudin-5 protein expression （P<0.05， P<0.01） and fluorescence intensity （P<0.01）， and decreased PLVAP protein expression （P<0.01） and fluorescence intensity （P<0.05， P<0.01）， as well as MMP-2 （P<0.05， P<0.01） and MMP-9 （P<0.01） expression. NHQXW-H downregulated p-Akt （P<0.05）， p-ERK1/2 （P<0.05）， p-STAT3 （P<0.01）， and p-YAP （P<0.05）， with the most significant effect observed on STAT3 phosphorylation. ConclusionNHQXW effectively alleviates neurological deficits and BBB injury in ICH mice with Tanre Fushi syndrome， primarily by inhibiting STAT3 activation.

Thermal ablation, an established minimally invasive technique, is increasingly utilized in treating thyroid nodules and microthyroid papillary carcinoma.Compared to conventional surgery, it offers advantages including minimal trauma, rapid recovery, and fewer complications.Recent technological advances have revealed its potential for managing primary hyperthyroidism. This review examines current evidence on thermal ablation applications in hyperthyroidism, analyzes its efficacy and safety, and discusses future challenges to inform clinical practice and research.

Objective:To evaluate the efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy.Methods:In this multicenter, non-inferiority, randomized controlled trial, 300 American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 18-60 yr, with body mass index of 18-28 kg/m 2, who underwent daytime laparoscopic cholecystectomy under general anesthesia with tracheal intubation at Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Jinhua Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou First People′s Hospital Affiliated to Westlake University School of Medicine, Ningbo No. 2 Hospital, and the Second Affiliated Hospital of Nanchang University from August 2021 to August 2023, were selected and divided into 2 groups ( n=150 each) using a random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced as follows: Sufentanil was intravenously injected at a rate of 0.5 μg/kg, remimazolam was intravenously injected at a rate of 0.3 mg/kg in group R, propofol was intravenously injected at a rate of 2.0-2.5 mg/kg in group P, and cisatracurium besilate was intravenously injected at a rate of 0.2 mg/kg after loss of consciousness in two groups. The patients were mechanically ventilated after tracheal intubation. Anesthesia was maintained as follows: Remimazolam was intravenously injected at a rate of 0.5-1.0 mg·kg -1·h -1 in group R, propofol was intravenously injected at a rate of 4-10 mg·kg -1·h -1 in group P, and remifentanil was intravenously infused at a rate of 0.25-2.00 μg·kg -1·min -1, maintaining intraoperative bispectral index value of 40-60. The success rate of sedation was recorded, and non-inferiority tests were conducted. The time to loss of consciousness, emergence time, extubation time, recovery time of orientation, time of stay in post-anesthesia care unit and occurrence of delayed emergence were recorded. Liver function and renal function were measured before operation and within 24 h after operation. The occurrence of abnormal alanine transaminase, abnormal aspartate transaminase, abnormal creatinine and abnormal urea was recorded. The occurrence of adverse reactions during and after operation was recorded. Results:The success rates of sedation were 98.6% and 99.3% in group R and group P, respectively, there was no statistically significant difference in the success rate of sedation between the two groups ( P>0.05), and the difference in the success rates of sedation between the two groups was -0.007 (95% confidence interval-0.0301-0.0161), which met the pre-set non-inferiority criteria(95% confidence interval >-0.055). Compared with group P, the time to loss of consciousness and recovery time of orientation were significantly prolonged, and the incidence of delayed emergence was increased ( P<0.05), and no statistically significant changes were found in the emergence time, extubation time, time of stay in post-anesthesia care unit and severity of postoperative nausea and vomiting in group R ( P>0.05). There was no statistically significant difference in the abnormal rates of alanine transaminase, aspartate transaminase, creatinine and urea before and after operation between the two groups ( P>0.05). Conclusions:The efficacy of remimazolam-based anesthesia in daytime laparoscopic cholecystectomy is not inferior to that of propofol-based anesthesia.

Objective:To investigate the efficacy of fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet count ratio (APRI), liver stiffness value (LSM), and Agile 3+ score and their combined model in predicting advanced-stage liver fibrosis in patients with chronic hepatitis B (CHB) combined with metabolic-associated fatty liver disease (MAFLD).Methods:A multicenter retrospective cohort study was conducted on the BMOVE population.Nine hundred twenty CHB cases combined with MAFLD who underwent liver biopsy at seven medical centers in China from April 2006 to December 2023 were included. The patients were divided into advanced-stage liver fibrosis (159 cases) and non-advanced-stage liver fibrosis (761 cases) according to the Scheuer's scoring system.The area under the receiver operating characteristic curve (AUROC), decision curve, and calibration curve analysis were used to evaluate the efficacy of the firbrosis-4 index (FIB-4) score, NFS score, APRI index, LSM, and Agile 3+ score and their combined model in predicting advanced-stage fibrosis. The liver fibrosis grade of all patients was diagnosed by liver biopsy. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each scoring model and combined model, as well as the proportion of correctly classified patients, were calculated based on different cutoff values.Results:AUROC analysis showed that Agile 3+ (0.814, 95% CI: 0.787-0.838) and LSM (0.805, 95% CI: 0.778-0.829) had similar accuracy and were superior to FIB-4 (0.721, 95% CI: 0.691-0.749), NFS (0.687, 95% CI: 0.656-0.716) and APRI ( 0.689, 95% CI: 0.658-0.718); however, HBV DNA level and HBV e antigen status had no effect on this outcome. Decision curve analysis showed that interventions based on LSM and Agile 3+ had provided higher net benefits compared with serological scores. Calibration curves showed that Agile 3+ had better predicitive accuracy than all other models. Agile 3+ had the highest PPV (0.54), minimal uncertainty interval (11.6%), and the highest proportion of correctly classified patients (76%); followed by LSM (PPV: 0.43, uncertainty interval: 15.5%, correct classification rate: 66%), and FIB-4 (PPV: 0.42, uncertainty interval: 26.1%, correct classification rate: 62.6%) in terms of identifying advanced-stage liver fibrosis. Combined model analysis demonstrated that FIB-4 combined with Agile 3+ had improved the correct classification rate and reduced the proportion of missed patients compared with FIB-4 combined with LSM. Conclusion:The Agile 3+ score is superior than LSM, FIB-4, NFS, and APRI index at identifying advanced-stage fibrosis in patients with CHB combined with MAFLD. This study supports the use of FIB-4 index combined with Agile 3+ for risk stratification in patients with CHB combined with MAFLD.

O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer Escherichia coli HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing aspB, aspA, and thrA^C1034T) were enhanced to obtain an initial strain accumulating 13.37 g/L OAH. Subsequently, the co-factor synthesis genes were integrated to supply reducing power and energy, which increased the yield to 15.79 g/L. The OAH yield of the engineered strain OAH28 was further increased to 17.49 g/L by strengthening the acetic acid reuse pathway, improving the supply of acetyl-CoA, and regulating the expression of MetX from different sources. Finally, in a 5 L fermenter, OAH28 achieved an OAH titer of 47.12 g/L, with a glucose conversion rate of 32% and productivity of 0.59 g/(L·h). The results lay a foundation for increasing the OAH production by metabolic engineering and give insights into the industrial production of OAH.
Metabolic Engineering/methods* ; Escherichia coli/genetics* ; Homoserine/biosynthesis* ; Fermentation

Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10～12 weeks old,weighing 20～25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.

Objective:To investigate the effects and mechanisms of angiotensin-converting enzyme 2 (ACE2) and Captopril (CAP) on mechanical ventilation-induced lung injury (VILI) in mice.Methods:Seventy-two healthy male BALB/c mice were randomly assigned (using a random number table) into six groups ( n=12 per group): normal control (NC) group, VILI group, ACE2 group, VILI+ACE2 group, CAP group, and VILI+CAP group. One hour prior to mechanical ventilation, the ACE2 and VILI+ACE2 groups were intraperitoneally injected with ACE2 at a dose of 0.1 mg/kg, while the CAP and VILI+CAP groups were intraperitoneally injected with CAP at a dose of 2.5 mg/kg. Following mechanical ventilation, serum samples were collected and enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors [platelet activating factor (PAF), endothelin-1 (ET-1), soluble intercellular adhesion molecule-1 (sICAM-1), prostaglandin E2 (PGE2)] and cardiovascular system related indicators [von Willebrand factor (vWF), thrombomodulin (TM), angiotensin (Ang) (1-9), Ang (1-7), prostacyclin I 2 (PGI2)]. Bronchoalveolar lavage fluid (BALF) was gathered, and total protein concentration was determined using BCA method, and sICAM-1 levels were measured by ELISA. Lung tissues were collected and subjected to hematoxylin and eosin staining (HE staining) for the assessment of pathological lung injury and lung injury scoring. Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were utilized to detect the relative expression levels of ACE2 protein and mRNA, respectively. Statistical analysis was performed using IBM SPSS 20.0 software. Intergroup comparisons were conducted using one-way analysis of variance followed by the least significant difference (LSD) test. Results:No statistically significant differences were observed in the levels of PAF, ET-1, sICAM-1, vWF, TM, Ang(1-9), Ang(1-7), and PGI2 in serum and lung tissues between the ACE2/CAP groups and the NC group (all P>0.05). Compared with the VILI group, the VILI+ACE2 and VILI+CAP groups exhibited significantly decreased serum and lung tissue levels of PAF, ET-1, sICAM-1, and vWF (all P<0.05), while the levels of TM, Ang(1-9), Ang(1-7), and PGI2 were significantly increased (all P<0.05). Pathological lung injury was alleviated, and the lung wet/dry weight ratio was significantly reduced (all P<0.05) in the VILI+ACE2 and VILI+CAP groups. Furthermore, both ACE2 protein and mRNA expression levels were significantly increased in these groups (all P<0.05). Conclusion:Both ACE2 and CAP can inhibit inflammation and protect the cardiovascular system, possibly by promoting the ACE2/Ang(1-9)/Ang(1-7) axis, thereby exerting a protective effect against VILI.

Annexin A3（ANXA3）is a member of the membrane associated protein family. It has two subtypes of 36 kDa and 33 kDa. Its gene is located on the fourth chromosome of human. ANXA3, widely expressed in human bone marrow, lung, placenta, prostate and thyroid, is closely related to several biological processes such as exoplasmosis, vascular production, fat cell maturity, and white blood cell migration. Studies have found that ANXA3 is abnormally expressed in various diseases including cancer, cardiovascular disease and inflammation. It can regulate multiple signaling pathways such as JNK, NF-κB, PI3K/AKT, and may become a potential drug target for treatment of related diseases. The structure, functions, the link with diseases and related mechanisms of ANXA3 were summarized in this paper, which could provide reference for ANXA3 related research.

With the continuous development of imaging techniques such as magnetic resonance imaging,the detection rate of brain metastases is increasing.Although the incidence rate of cystic brain metastasis is far lower than that of solid brain metastasis,patients with cystic brain metastasis are in urgent condition and have obvious space occupying effect,which is an urgent clinical problem.Previous literature has reported that cystic brain metastasis is more common in breast cancer and lung adenocarcinoma,especially in lung cancer patients with positive driver gene.This article reports a case of small cell lung cancer with cystic brain metastasis,which started with neurological symptoms,and was clinically cured under a multidisciplinary diagnosis and treatment model.Through dynamic imaging evaluation and molecular residual lesion detection,the patient can avoid overtreatment and achieved a relatively higher quality of life on the basis of prolonging survival.