Objective:Cardiac arrest (CA) represents a significant public health challenge, posing a substantial threat to individual health and survival. To enhance the survival rates of patients experiencing out-of-hospital cardiac arrest (OHCA), Baoan District in Shenzhen City has undertaken exploratory initiatives and practical interventions, yielding promising preliminary outcomes.Methods:1.Innovate emergency medical services by developing a "four-circle integration" system that connects to the hospital. This system encompasses the social emergency medical system, the out-of-hospital emergency medical system, the in-hospital emergency medical service system, and the intensive care treatment system. 2.Develop a comprehensive model for the construction of a social emergency medical training system, characterized by party leadership, government oversight, departmental coordination, professional guidance, technological support, and community involvement, termed the "Baonan Model." Additionally, establish evaluation criteria to assess the effectiveness of the social emergency medical training system in Baonan District; 3. Develop a cardiac arrest registration system and a social emergency medical training management system for Baonan District; 4. Enhance the proficiency in treatment techniques and the quality of cardiopulmonary resuscitation among emergency medical professionals; 5. Strengthen and advance the development of a "five-minute social rescue network" to address the critical "emergency window period." .Result:In Baonan District, 9.18% of the public is trained in emergency medical skills. The bystander CPR rate for OHCA is 26.11%, AED use is at 4.78%, the 30-day survival rate is 6.31%, and the discharge survival rate is 4.44%.Conclusion:The implementation of the aforementioned measures can substantially enhance the survival rate of patients experiencing OHCA at the time of discharge.

Objective To understand the research hotspots and development trend of Hedyotidis Herba;To provide reference for related clinical studies.Methods The literature on Hedyotidis Herba was retrieved from CNKI,Wanfang Data,VIP and CBM from January 1,2003 to September 5,2023.NoteExpress 3.7 software was used to manage the bibliothems,and CiteSpace 6.2.R2 software was used to visualize the authors,institutions and keywords.Results Totally 2 713 articles were included,and the annual number of publications showed a fluctuating upward trend.There were 617 source journals,among which Shaanxi Journal of Traditional Chinese Medicine published the most articles(136).799 authors were involved,and the core authors included Liu Jian,Lin Jiumao,Peng Jun,etc.The main research institutions were Nanjing University of Chinese Medicine,Shandong University of Traditional Chinese Medicine,Guangzhou University of Chinese Medicine and so on.In recent years,high-frequency keywords were experience of famous doctors,data mining,medication law,apoptosis,lung cancer,liver cancer,etc.The research frontier involved the mechanism,data mining and molecular docking.Conclusion The study of the Hedyotidis Herba mainly focuses on disease treatment,compatibility application,component analysis,mechanism,and the experience summary of clinical application of the Hedyotidis Herba.Data mining for medication law of famous doctors,prediction of potential drug targets through network pharmacology and molecular docking technology and exploration of their mechanisms are the research trends in this field.

Objective To investigate the effect of Yiqi Jiedu Recipe(YQ)on the proliferation,migration,and invasion of nasopharyngeal carcinoma cells,and to explore its mechanisms of action on proliferation,migration,and invasion through the TGF-β1/SMAD3 signaling pathway.Methods(1)The 5-8F cells were divided into four groups:solvent control group,YQ 0.5 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and 5-fluorouracil 2 μg·mL-1 group.Cell proliferation was monitored using real-time cell analysis(RTCA).Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using the Western Blot method.(2)The 5-8F cells were divided into five groups:solvent control group,TGF-β1 10 ng·mL-1 group,TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group,YQ 1.0 mg·mL-1 group,and LY3200882 10 μmol·L-1 group.Cell proliferation was monitored using RTCA.Wound healing experiment was conducted to assess cell migration.After 24 hours of drug intervention,transwell assay was employed to measure cell invasion.The protein expression levels of β-catenin,E-cadherin,N-cadherin,TGF-β1,and SMAD3 in the cells were evaluated using Western Blot.(3)The nude mice were randomly assigned into the model group,YQ group,and 5-fluorouracil group.Subcutaneous injection of 5-8F cell suspension was performed to establish the xenograft nude mouse model of nasopharyngeal carcinoma.After the tumors reached a certain size,the 5-fluorouracil group received intraperitoneal injection of 5-Fu once every 2 days,while the other groups were orally administered corresponding drugs once a day for three consecutive weeks.Tumor volume was measured every 3 days.Western Blot was conducted to assess the protein expression levels of β-catenin,E-cadherin,and N-cadherin in the tissues of each group.Results Compared with the solvent control group,the proliferation curves of 5-8F cells in the YQ(0.5 mg·mL-1,1.0 mg·mL-1)groups showed a decrease.The migration and invasion abilities of the cells were both reduced(P＜0.05,P＜0.01).Additionally,the expression of E-cadherin protein significantly increased(P＜0.01),while the protein expression of β-catenin,N-cadherin,TGF-β1,and SMAD3 all decreased(P＜0.05,P＜0.01).Compared with the model group,the transplanted tumor volume of nasopharyngeal carcinoma in the YQ group significantly decreased(P＜0.05).Furthermore,the protein expression of β-catenin and N-cadherin in the transplanted tissues of the YQ group was significantly downregulated(P＜0.05,P＜0.01),while the expression of E-cadherin protein was significantly upregulated(P＜0.01).After the addition of the activator and inhibitor of TGF-β1 signaling pathway,compared with the YQ 1.0 mg·mL-1 group,the TGF-β1 10 ng·mL-1+YQ 1.0 mg·mL-1 group showed a significant increase in the expression of TGF-β1,SMAD3,β-catenin,and N-cadherin proteins(P＜0.05,P＜0.01)and obvious enhancement of the abilities of cell proliferation,migration,and invasion(P＜0.01).Conclusion Yiqi Jiedu Recipe can inhibit the proliferation,migration,and invasion by regulating the TGF-β1/SMAD3 signaling pathway.

Tacrolimus (FK506) is a 23-membered macrolide with immunosuppressant activity that is widely used clinically for treating the rejection after organ transplantation. The research on tacrolimus production was mainly focused on biosynthesis methods, within which there are still some bottlenecks. This review summarizes the progress made in tacrolimus biosynthesis via modification of metabolic pathways and control of fermentation process, with the hope to address the technical bottlenecks for tacrolimus biosynthesis and improve tacrolimus production by fermentation engineering and metabolic engineering.
Tacrolimus ; Immunosuppressive Agents ; Fermentation ; Macrolides ; Anti-Bacterial Agents

Objective:To investigate the correlation between pulmonary arteriovenous fistula (PAVF) and ischemic stroke, and to improve the diagnosis and treatment of embolic strokes of undetermined source.Methods:Five patients with ischemic stroke caused by PAVF admitted to Xiangya Hospital of Central South University from January 2017 to December 2020 were collected. The diagnosis, treatment and prognosis of stroke caused by PAVF were summarized based on literature review.Results:Among the 5 patients, 1 is male and 4 are females, with age of (34.4±9.3) years. Weakness of unilateral limb, slurred speech, vision changes, drooping eyelids, etc., were the first manifestations of stroke. The location of cerebral infarction was indefinite. In this study, 5 patients were all isolated PAVF, including 3 cases of left lower lung, 1 case of left upper lung and 1 case of right lower lung. All 5 patients underwent interventional therapy, were followed-up for 6 months and 12 months after surgery, and none of them had a new stroke attack, and only 1 case had recanalization of PAVF.Conclusions:PAVF is a rare vascular lesion, stroke caused by which is even rarer, with a lack of specificity in clinical manifestations. For young patients with unexplained embolic stroke, if the stroke has a sudden onset, the anterior and posterior circulation can be involved, and multiple vascular distribution regions are often involved, and it is difficult to find a clear emboli basis, with manifestations such as hypoxemia, PAVF should be considered. Percutaneous catheter intervention for PAVF is safe and effective, and is the preferred method for the treatment of PAVF.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Objective:To study the features as well as the diagnosis and differential diagnosis values by conventional MRI morphometrics in different clinical subtypes of progressive supranuclear palsy(PSP).Methods:Forty five patients with PSP were included, comprising three PSP subtypes: 15 cases of Richardson's syndrome(PSP-RS), 15 cases of Parkinson's syndrome(PSP-P)and 15 cases of progressive frozen gait(PSP-PFG). In addition, three control groups were established: 15 cases of multiple system atrophy-Parkinson's syndrome(MSA-P), 30 cases of primary Parkinson's disease(PD)and 40 healthy controls(HC). Midbrain area-to-Pons area ratio(M/P), Magnetic Resonance Parkinsonism Index(MRPI, MRPI2.0), width ratio of middle cerebellar peduncle to superior cerebellar peduncle(MCP/SCP), Midbrain-to-Pons ratio(MTPR), Angle of cerebral peduncle(A cp), third ventricle width/frontal horns width ratio(V 3rd/FH), and Humming bird sign rating scale(HBS-RS)scores were calculated.Diagnostic sensitivity and specificity were performed by ROC curve to assess the accuracy of these imaging indicators in the diagnosis and differential diagnosis of PSP and its subtypes. Results:The MRPI, MRPI2.0, MCP/SCP and HBS-RS scores were significantly higher in PSP group than in other control groups( H=69.351, 66.776, 33.926 and 84.694, all P<0.05), while M/P and MTPR were significantly lower in PSP group than in other control groups(H=60.101 and 77.276, all P<0.05). PSP group also had higher V 3rd/FH compared with PD or HC group( F=17.168, P<0.05), but not with MSA-P group( Z=-1.602, P>0.05). The above differences also existed between each PSP subgroup and control groups.Among PSP subgroups, PSP-PFG subgroup had a larger A cp than did PSP-RS( Z=-2.510, P<0.05), and had higher HBS-RS score than did PSP-P group( Z=-2.380, P<0.05). No significant differences in other MRI morphometric indexes were identified among PSP subtypes.The M/P, MRPI, MTPR, MRPI2.0, HBS-RS score showed good accuracy in diagnosing PSP and its each subgroup, with HBS-RS score being the most accurate indicator, when the cutoff value was 2, the AUC values were all higher than 0.99, and the sensitivity and specificity were all above 90%.PSP and its subtypes were best distinguished from MSA-P by MRPI, when the cutoff value was 9.94, the AUC values were all higher than 0.90, with the sensitivity of 100% and specificity of 86.67%.PSP and its subtypes were best distinguished from PD by MTPR, AUC values were all above 0.95, with slightly different cutoff values.Almost all the morphological measurement parameters failed to show significant sensitivity and specificity in discriminating subtypes of PSP.The sensitivity and specificity of almost all MRI morphometry indicators in differentiating different subtypes of PSP are not high. Conclusions:MRI morphometrics have a high value both in the diagnosis of PSP and its subtypes, and also in specific application fields.MRI morphometrics have a limited value in discriminating PSP subtypes.

OBJECTIVE: To investigate the prevalence, risk factors, duration and outcome of delirium in intensive care unit (ICU) patients. METHODS: A prospective observational study was conducted for critically ill patients admitted to the department of critical care medicine, the Affiliated Hospital of Guizhou Medical University from September to November 2021. Delirium assessments were performed twice daily using the Richmond agitation-sedation scale (RASS) and confusion assessment method of ICU (CAM-ICU) for patients who met the inclusions and exclusion criteria. Patient's age, gender, body mass index (BMI), underlying disease, acute physiologic assessment and chronic health evaluation (APACHE) at ICU admission, sequential organ failure assessment (SOFA) at ICU admission, oxygenation index (PaO₂/FiO₂), diagnosis, type of delirium, duration of delirium, outcome, etc. were recorded. Patients were divided into delirium and non-delirium groups according to whether delirium occurred during the study period. The clinical characteristics of the patients in the two groups were compared, and risk factors for the development of delirium were screened using univariate analysis and multivariate Logistic regression analysis. RESULTS: A total of 347 ICU patients were included, and delirium occurred in 57.6% (200/347) patients. The most common type was hypoactive delirium (73.0% of the total). Univariate analysis showed statistically significant differences in age, APACHE score and SOFA score at ICU admission, history of smoking, hypertension, history of cerebral infarction, immunosuppression, neurological disease, sepsis, shock, glucose (Glu), PaO₂/FiO₂ at ICU admission, length of ICU stay, and duration of mechanical ventilation between the two groups. Multivariate Logistic regression analysis showed that age [odds ratio (OR) = 1.045, 95% confidence interval (95%CI) was 1.027-1.063, P < 0.001], APACHE score at ICU admission (OR = 1.049, 95%CI was 1.008-1.091, P = 0.018), neurological disease (OR = 5.275, 95%CI was 1.825-15.248, P = 0.002), sepsis (OR = 1.941, 95%CI was 1.117-3.374, P = 0.019), and duration of mechanical ventilation (OR = 1.005, 95%CI was 1.001-1.009, P = 0.012) were all independent risk factors for the development of delirium in ICU patients. The median duration of delirium in ICU patients was 2 (1, 3) days. Delirium was still present in 52% patients when they discharged from the ICU. CONCLUSIONS The prevalence of delirium in ICU patients is over 50%, with hypoactive delirium being the most common. Age, APACHE score at ICU admission, neurological disease, sepsis and duration of mechanical ventilation were all independent risk factors for the development of delirium in ICU patients. More than half of patients with delirium were still delirious when they discharged from the ICU.
Humans ; Prevalence ; Critical Care ; Risk Factors ; Sepsis ; Intensive Care Units

Objective:To evaluate the efficacy and safety of apatinib in combination with chemoradiotherapy for head and neck squamous cell carcinoma (HNSCC).Methods:37 patients orally received apatinib at 250 mg/d during concurrent chemoradiotherapy until completion of radiotherapy, complete remission assessed by imaging examination, the onset of unacceptable toxicity or death. Baseline characteristics, objective response rates (ORR) and adverse events were assessed in all enrolled patients with complete baseline and safety data. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic factors were statistically identified using Cox regression models.Results:The ORR was 85%(95% CI: 72%-98%). The median PFS was 17.9 months and the 2-year OS rate was 62%(95% CI: 48%-80%). Ineffective short-term efficacy ( HR=0.035, 995% CI: 0.02-0.652, P=0.025) was an independent risk factor for poor OS. In addition, ineffective short-term efficacy ( HR=0.104, 95% CI: 0.017-0.633, P=0.014) and lymphocytopenia ( HR=17.539, 95% CI: 2.040-150.779, P=0.009) were independent risk factors for poor PFS. Common adverse events (>60%) included lymphocytopenia (76%), leukopenia (68%) and irradiation-induced mucosal injury (65%). The most common treatment-associated grade 3 adverse event was lymphopenia (49%). Conclusions:Apatinib combined with chemoradiotherapy yield significant anti-tumor activity for HNSCC with controllable toxicity. For patients with advanced HNSCC, short-term efficacy and lymphocytopenia may be potential predictors for clinical efficacy of apatinib combined with chemoradiotherapy.

Background: Chicken anemia virus (CAV) causes chicken infectious anemia, which results in immunosuppression; the virus has spread widely in chicken flocks in China. Objectives: The aim of this study was to understand recent CAV genetic evolution in chicken flocks in Guangxi Province, southern China. Methods: In total, 350 liver samples were collected from eight commercial broiler chicken farms in Guangxi Province in southern China from 2018 to 2020. CAV was detected by conventional PCR, and twenty CAV complete genomes were amplified and used for the phylogenetic analysis and recombination analysis. Results: The overall CAV-positive rate was 17.1%. The genetic analysis revealed that 84 CAVs were distributed in groups A, B, C (subgroups C1-C3) and D. In total, 30 of 47 Chinese CAV sequences from 2005-2020 belong to subgroup C3, including 15 CAVs from this study. There were some specific mutation sites among the intergenotypes in the VP1 protein. The amino acids at position 394Q in the VP1 protein of 20 CAV strains were consistent with the characteristics of a highly pathogenic strain. GX1904B was a putative recombinant. Conclusions Subgroup C3 was the dominant genotype in Guangxi Province from 2018–2020.The 20 CAV strains in this study might be virulent according to the amino acid residue analysis. These data help improve our understanding of the epidemiological trends of CAV in southern China.