Randomized controlled trial (RCT) are considered the "gold standard" for evaluating the causal effects of interventions on outcome measures. However, due to high research costs and ethical constraints, conducting RCT in clinical practice, especially in the surgical field, faces numerous challenges such as difficulties in subject recruitment, implementation of blinding, and standardization of interventions. In such cases, using real-world data to perform causal inference under the framework of target trial emulation (TTE), based on the principles of RCT design, helps to identify and reduce biases arising from design flaws in traditional observational studies, such as immortal time bias, confounding, selection bias, or collider bias. This approach can produce high-quality evidence comparable to that of RCT, thereby enhancing the clinical guidance value of real-world data studies. However, TTE has limitations, such as the inability to completely eliminate confounding, high quality requirements for source data, and the current lack of reporting standards. Therefore, researchers should be fully aware of these limitations to avoid making incorrect causal inferences. This article intends to provide an overview of the TTE framework, implementation points, application scope, application cases, and advantages and disadvantages of the framework.

Objective:To evaluate the associations of sociodemographic characteristics and lifestyle factors with longevity status in older adults in China.Methods:After excluding those born after 31 st December 1938, a total of 51 870 older adults from the China Kadoorie Biobank (CKB) were included. The attained age was defined according to the survival age or age on 31 st December 2018. According to the attained age, the old persons were categorized into non-longevity (died before age 80 years) and longevity (attained age ≥80 years). The longevity group was further divided into two groups: longevity with death occurring before 2019, and longevity and survival to 2019. The information about socio-demographic characteristics and lifestyles was collected at the 2004-2008 baseline survey. Multinomial logistic regression models were used to analyze the associations between exposure factors and outcomes by taking the non-longevity group as the reference group. Results:A total of 51 870 older adults aged 65-79 years in the baseline survey were included for analysis. During a follow-up for (10.2±3.5) years, 38 841 participants were longevity, and 30 354 participants still survived at the end of 2018. Compared to men, rural populations, non-married individuals, those with an annual household income of less than 10 000 yuan, and those with education levels of primary school or below, the adjusted ORs(95% CI) for longevity and survival to 2019 in women, urban residents, married individuals, those with annual household incomes ≥20 000 yuan, and those with education levels of college or university were 1.68 (1.58-1.78), 1.69 (1.61-1.78), 1.15 (1.10-1.21), 1.44 (1.36-1.53), and 1.32 (1.19-1.48), respectively. The OR (95% CI) for longevity and survival to 2019 was 1.09 (1.08-1.10) for those with an increase of 4 MET-hour/day in total physical activity level. With those who never or almost never smoked, had no alcohol drinking every week, had normal weight (BMI: 18.5-23.9 kg/m 2), and WC <85 cm (man)/<80 cm (woman) as the reference groups, the ORs(95% CI) of longevity and survival to 2019 were 0.64 (0.60-0.69) for those smoking ≥20 cigarettes per day, 1.29 (1.14-1.46) for those with alcohol drinking every week, 1.13 (1.01-1.26) for those with pure alcohol drinking <30 g per day, 0.56 (0.52-0.61) for those being underweight, 1.27 (1.19-1.36) for those being overweight, 1.23 (1.11-1.36) for those with obesity, and 0.86 (0.79-0.93) for those with central obesity. Further stratified analysis by WC was performed. In the older adults with WC <85 cm (man)/<80 cm (woman), the ORs (95% CI) of longevity and survival was 1.80 (1.69-1.92) for those with each 5 kg/m 2 increase in BMI and 1.02 (0.96-1.08) for those with WC ≥85 cm (man)/≥80 cm (woman). There was a statistically significant difference in the association between BMI and longevity between the two WC groups (interaction test P<0.001). Conclusion:This study showed that women, the married, those with higher socioeconomic status and education level, and those with healthy lifestyles were more likely to achieve longevity.

Mirabilis jalapa L. is a plant of the family of Miraceae, native to tropical America and introduced to China during the Ming Dynasty. Its main medicinal part is the root. After sorting, it was found that the research on the medicinal properties of the Mirabilis Radixis incomplete, and the records of medicinal properties do not fully match the current application, and there is a situation of "the raw and processed for different treatments". This study further explored its medicinal properties. The Mirabilis Radix is bitter, pungent, and slight cold; belonging to the bladder, liver, and stomach meridians; it has the functions of clearing heat and dampness, detoxifying and reducing swelling, promoting blood circulation and regulating menstruation, dispelling wind and dampness, and nourishing yin. It was taken orally, with decoction, and adults should take 15-30 g, not in the form of original powder. People with spleen and stomach deficiency and cold should take it with caution, and pregnant women should not take it; for external use, an appropriate amount of fresh products should be applied and mashed. Processed Mirabilis Radix, recorded by Tujiazu medicine and Uyghur medicine, after boiling or steaming, the medicinal properties change and the nourishing effect is enhanced, but there is a lack of relevant research. Further exploration of the medicinal properties of the Mirabilis Radix can provide reference for clinical application, standard improvement, and product development.

Diabetic peripheral neuropathy(DPN)is a common and devastating complication of diabetes,for which effective therapies are currently lacking.Disturbed energy status plays a crucial role in DPN pathogenesis.However,the integrated profile of energy metabolism,especially the central carbohy-drate metabolism,remains unclear in DPN.Here,we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry(HPIC-MS/MS)to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats.Furthermore,JinMaiTong(JMT),a traditional Chinese medicine(TCM)formula,was found to be effective for DPN,improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration.JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions,including excessive glycolysis restoration,tricarboxylic acid cycle improvement,and increased adenosine triphosphate(ATP)generation.Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions,which was remarkably corrected by JMT treatment.In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α).Our results expand the thera-peutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs,such as JMT,as an effective strategy for its treatment.

African swine fever(ASF)is an acute and highly pathogenic hemorrhagic disease of pigs,causing huge economic losses to pig industry.In order to quantitatively detect clinical samples of ASF and inactivated ASFV antigens,the IgG of ASF positive serum was used as capture anti-body and the HRP-labeled p72 monoclonal antibody was used as detecting antibody.The standard curve was drawn with the cell-cultured ASFV,and a sandwich ELISA detection of antigen was es-tablished.The specificity,sensitivity and stability of the method were evaluated.The effects of dif-ferent inactivation methods and adjuvant addition on antigen detection were further evaluated.The results showed that the minimum detection limits of the recombinant protein and the ASFV were 0.1 mg/L and 103.7 TCID50/mL,respectively.There was no cross-reaction with five common porcine pathogenic viruses,and the coefficient variations between batches was less than 10％.The total co-incidence rate with real-time fluorescence quantitative PCR was 92％(23/25).The sensitivity of antigen detection was significantly reduced when antigen was treated by BEI inactivation,and the detection results were severely interfered by aluminum adjuvant and nano-adjuvant.In summary,the sandwich ELISA antigen detection method established is specific,sensitive,and repeatable,with a good consistency to the qPCR method,which provides an effective clinical diagnostic meth-od for ASFV antigen.

Objective:To evaluate the predictive value of angiopoietin-2 (Ang-2) for the prognosis in patients with acute respiratory distress syndrome (ARDS).Methods:A retrospective study was conducted, and ARDS patients admitted to the department of emergency medicine of Tongde Hospital of Zhejiang Province from December 2020 to September 2022 were enrolled. General information including gender, age, causes of ARDS, disease severity scores, plasma Ang-2 levels before treatment and at 24, 48, and 72 hours after treatment, and record the 60-day prognosis were collected. Differences in clinical data between groups were compared. Multivariate Logistic regression analysis was used to identify the independent risk factors affecting the 60-day prognosis of ARDS patients, and the receiver operator characteristic curve (ROC curve) was plotted to assess the predictive value of these risk factors for patient outcomes. Pearson correlation analysis was used to assess the correlation between Ang-2 and pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI).Results:A total of 132 ARDS patients were included, of which 49 patients died within 60 days and 83 patients survived. In the death group, plasma Ang-2 levels showed a gradually increasing trend, all significantly higher than before treatment (μg/L: 12.75±1.81, 12.74±1.48, 13.45±2.21 vs. 5.98±0.57, all P < 0.05), while the trend in the survival group was not significant. At 24, 48, and 72 hours after treatment, plasma Ang-2 levels in the death group were significantly higher than those in the survival group (μg/L: 12.75±1.81 vs. 7.48±1.22, 12.74±1.48 vs. 7.41±1.19, 13.45±1.41 vs. 6.88±1.41, all P < 0.05). After adjusting for confounding variables, increased plasma Ang-2 level was an independent risk factor for prognosis in ARDS patients within 60 days [odds ratio ( OR) = 0.998, 95% confidence interval (95% CI) was 0.997-0.999, P < 0.01]. ROC curve analysis demonstrated that Ang-2 levels had predictive value for prognosis in ARDS patients [area under the ROC curve (AUC) = 0.985, 95% CI was 0.971-1.000, approximate maximum Youden's index 0.867, optimal cut-off value 8.43 μg/L]. Pearson correlation analysis showed that plasma Ang-2 levels were positively correlated with PVPI and EVLWI ( r values were 0.620 and 0.712 respectively, both P < 0.01). Conclusions:Elevated level of Ang-2 is an independent risk factor for increased mortality in patients with ARDS. Higher Ang-2 levels within 72 hours after treatment may indicate poorer prognosis.

Objective To explore the mechanism of Yangxue Qingnao Granules(Siwu Decoction modified)in the treatment of hypertension based on network pharmacology and molecular docking.Methods The chemical composition analysis results of Yangxue Qingnao Granules in the early stage of the research group were used as the basis for the screening of active compounds.The oral bioavailability≥30%and drug-likeness≥0.18 were used as the screening conditions,and the blood components were supplemented in combination with the literature.TCMSP,chemical professional database and SWISS database were used to predict the targets of potential active compounds of Yangxue Qingnao Granules.Hypertension-related targets were obtained through GeneCards and DiGSeE databases.The intersection of the targets related to hypertension disease and the targets of the potential active compounds of Yangxue Qingnao Granules(common targets)is the potential target of Yangxue Qingnao Granules for the treatment of hypertension.The potential targets were matched with the potential active compounds of Yangxue Qingnao Granules to obtain the antihypertensive active compounds of Yangxue Qingnao Granules.PPI analysis was performed on the potential targets of serum brain granules in the treatment of hypertension through the STRING database,and the core targets were screened according to the degree value.The David database was used to analyze the GO function and KEGG pathway enrichment of the core targets.The core targets with the top six degrees were selected as the docking target proteins,and molecular docking verification was performed with the antihypertensive active compounds.Results A total of 32 potential active compounds,161 active compound targets and 1 539 hypertension-related targets were obtained.After intersection,88 potential targets(common targets)of Yangxue Qingnao Granules in the treatment of hypertension were obtained,involving 29 antihypertensive active compounds.PPI analysis screened 14 core targets:PPARG,ACHE,IL4,CCL2,JUN,NOS3,APP,IL1B,CAT,PTGS2,CASP3,TP53,TNF,IL6,involving 158 GO entries and 13 signaling pathways.Five key active ingredients,chlorogenic acid,rosmarinic acid,paeoniflorin catechinic acid and aloe emodin,were obtained by molecular docking,which were combined with PTGS2,CASP3,TNF,CAT,TP53 and IL6,respectively.Conclusion Yangxue Qingnao Granules may act on core targets such as PTGS2 and CASP3 through key active components such as chlorogenic acid and rosmarinic acid,regulate key pathways such as TNF signaling pathway,MAPK signaling pathway and Toll-like receptor signaling pathway,and play a role in the treatment of hypertension through anti-inflammatory effects.

Objective:To explore whether thyroxine (T 4) could promote differentiated thyroid cancer (DTC) progression by binding to integrin α vβ 3in vitro and its downstream mechanism. Methods:Papillary thyroid cancer cell lines TPC-1, K1 and follicular thyroid cancer (FTC) cell line FTC133 were cultured in vitro, and the expressions of integrin α vβ 3 in those 3 DTC cell lines were determined with immunofluorescence and flow cytometry analysis. After the treatment of T 4, tetraiodo thyroacetic acid (Tetrac) and Arg-Gly-Asp (RGD) peptide alone or in combination, the proliferation and metastatic potential of DTC cell lines were detected by cell counting kit-8 (CCK-8), Transwell migration and invasion assays. The small interfering RNA (siRNA) transfection was used to verify whether integrin α v or β 3 subunit knockdown could reverse the effect of T 4 on DTC cells. The expression levels of downstream signaling proteins phosphorylated extracellular signal-regulated kinase (p-ERK)1/2 and total extracellular signal-regulated kinase (ERK)1/2 were detected by Western blot. The effects of mitogen-activated protein kinase kinase (MEK)1/2 inhibitor (GSK1120212) on the proliferation, migration and invasion of T 4-treated cells were detected. One-way analysis of variance and Tukey test were used for data analysis. Results:The integrin α vβ 3 expressions in TPC-1, K1 and FTC133 cells were all positive, with the relative mean fluorescence intensity (MFI) of 61.93±18.61, 16.89±2.43 and 32.36±0.83, and the percentages of positive cells of (94.38±1.30)%, (74.11±3.87)% and (50.67±1.78)%, respectively ( F values: 13.36 and 217.30, P=0.006 and P<0.001). Compared with control group, the proliferation, migration and invasion in the three DTC cell lines treated with T 4 were significantly enhanced (96 h, F values: 62.67-297.50, q values: 13.15-20.73, all P<0.001). T 4-induced cell proliferation, migration and invasion were markedly reversed by Tetrac or RGD (96 h, q values: 8.61-17.54, all P<0.001). T 4-induced cell proliferation, migration and invasion were also significantly inhibited by the knockdown of integrin α v or β 3 subunit (72 h, F values: 7.75-70.98, q values: 4.77-15.21, all P<0.05). Western blot results showed that the phosphorylation levels of ERK1/2 in DTC cells were significantly increased by T 4 treatment, and the T 4-induced activation of ERK1/2 signaling pathway could be blocked by Tetrac, RGD, integrin α v or β 3 subunit knockdown. T 4-induced cell proliferation, migration and invasion were significantly reversed by GSK1120212 (96 h, F values: 47.53-151.40, q values: 10.32-16.65, all P<0.001). Conclusion:T 4 can promote cell proliferation and metastasis of DTC cells by binding to integrin α vβ 3 and activating the ERK1/2 pathway.

Objective To evaluate the effect of electroacupuncture at Chize and Shangjuxu on the prognosis and respiratory dynamics in patients with acute respiratory distress syndrome(ARDS).Methods A prospective randomized controlled study was conducted to collect patients with ARDS admitted to the Department of Emergency Medicine of Tongde Hospital of Zhejiang Province from December 2020 to September 2022.A total of 142 patients with ARDS from the Department of Emergency Medicine of Tongde Hospital of Zhejiang Province were selected for this study.Seven patients were excluded due to rapid deterioration,3 patients withdrew the informed consent,and finally 132 patients were enrolled.According to the order of enrollment,they were randomly divided into the electroacupuncture group and the conventional treatment group based on the random number table.The conventional treatment group received conventional treatment for ARDS,while the electroacupuncture group combined with electroacupuncture at Chize and Shangjuxu,the treatment lasted for 30 minutes.The mortality at day 60 and secondary efficacy indicators such as hospital stay,ventilator-free days at 28 day,and mechanical ventilation time of two groups were compared,and the indicators of respiratory mechanics and oxygenation such as inhalation oxygen concentration(FiO2),tidal volume(VT),positive end-expiratory pressure(PEEP),plateau pressure(Pplat),lung static compliance(Cst),oxygenation index(PaO2/FiO2)were also compared.Then the Kaplan-Meier survival curves were drawn to compare the differences in cumulative survival rates within 60 days between the two groups.Results The mortality at day 60 in the electroacupuncture group was lower than that in the conventional treatment group[33.33％(22/66)vs.40.91％(27/66)],but the difference was not statistically significant(P>0.05),and the hospital stay in the electroacupuncture group was significantly shorter than that in the conventional treatment group(days:25.09±11.57 vs.30.21±15.94,P<0.05).The ventilator-free days at 28 days in the electroacupuncture group were significantly higher than those in the conventional treatment group(days:10.06±7.35 vs.7.67±5.72,P<0.05).There was no statistically significant difference in mechanical ventilation time between the two groups(days:15.70±9.05 vs.18.39±9.55,P>0.05).After 72 hours of treatment,the FiO2,VT,and PaCO2 levels in the electroacupuncture group were significantly lower than those in the conventional treatment group[FiO2:0.39±0.07 vs.0.44±0.09,VT(mL/kg):6.27±0.74 vs.6.62±0.74,PaCO2(mmHg,1 mmHg≈0.133 kPa):39.94±4.52 vs.41.95±4.19,all P<0.05].Conclusion Electroacupuncture at Chize and Shangjuxu can effectively shorten the course of ARDS and improve prognosis,which may be related to the improvement of respiratory dynamics by electroacupuncture treatment.

Androgen deprivation therapy is one of the main treatments for prostate cancer patients. In recent years, many studies have revealed that androgen deprivation therapy increases the risk of cardiovascular disease, which leads to the cause of death alongside tumor-related deaths. The mechanism may be related to the elevation of testosterone levels, follicle-stimulating hormone levels and unstable atherosclerotic plaque. Standardized cardiovascular disease management in this population is a key issue to improve survival and prognosis. This paper summarizes a management plan covering 5 areas, including history collecting and data examination, assessment, referral, health education, and regimen selection.