OBJECTIVE To standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Life science and medical research involving human beings cannot be separated from the support of research participants.The safety,health,and rights and interests of research participants are the primary considerations in clinical research,and their rights and interests include the right of compensation,privacy protection,health and so on.Protecting the compensation rights of research participants is a necessary responsibility of the research-related departments and personnel.Based on laws and regulations and literature review,and combined with practical experience,this paper made an in-depth discussion on compensation rights.It puts forward the types of compensation(conventional compensation,research-related damage compensation),compensation principles(necessity,timeliness,appropriateness,fairness),compensation elements(method,amount,plan,consent,notification,and reference of compensation),compensation under special circumstances(compensation for participants without or with limited informed consent ability and withdraw from the study midway),protection measures of compensation right(sponsor/contract research organizations,research institutions,research management departments,(main)researchers and research teams,ethics(review)committee).The compensation rights should be implemented to protect research participants.

With the reform of the medical and health system entering a critical period,public hospitals have also exposed new risks and challenges in economic operation.As an important means of hospital standardized management,internal control can better prevent and resolve the risk of hospital economic operation and ensure the sustainable operation of the hospital.By interpreting the requirements of current national policies on hospital internal control,it analyzes the functional positioning of financial and accounting supervision in hospital internal control,shares the internal control implementation path of sample hospitals from the perspective of financial and accounting supervision,and puts forward suggestions on strengthening internal control construction of public hospitals in the new era,in order to lay a good foundation for the high-quality development of hospitals.

Objective To establish an HPLC fingerprint of Dingdang Qigui Decoction and analyze and evaluate it using chemical pattern recognition technology;To determine the contents of 5 effective chemical components in Dingdang Qigui Decoction;To provide a basis for its quality control.Methods The analysis was performed on Agilent 5 TC-C18(2)column(250 mm×4.6 mm).The mobile phase comprised of acetonitrile-0.1%phosphoric acid aqueous solution with the gradient elution at a flow rate of 1.0 mL/min.The detection wavelength was set at 260 nm.The column temperature was maintained at 30℃and the injection volume was 10 μL.SPSS 26.0 and SIMCA 14.1 were used to perform clustering analysis and principal component analysis on the 10 batches of Didang Qigui Decoction.The landmark components for inter batch differences were selected through orthogonal partial least squares discriminant analysis(OPLS-DA).Results The HPLC fingerprint with eighteen common peaks of Didang Qigui Decoction in 10 batches of sample was established,and the similarities of samples were between 0.828 and 0.989.Five indicative components were identified and quantitatively analyzed by comparing with the reference substances,which were paeoniflorin,mauroisoflavone glucoside,hesperidin,cinnamaldehyde and aloe rhodopsin.The linear ranges was 10.000 0-320.000 0 μg/mL,2.500 0-80.000 0 μg/mL,10.000 0-320.000 0 μg/mL,10.000 0-320.000 0 μg/mL,0.078 1-5.000 0 μg/mL,respectively,and their mean recovery ranged from 100.30%to 104.09%.Clustering analysis and principal component analysis divided 10 batches of samples from Didang Qigui Decoction into 2 categories.Through OPLS-DA screening,hairy pistil isoflavone glycosides,paeoniflorin,and hesperidin were selected as landmark components for quality differences.Conclusion The quality evaluation method for Didang Qigui Decoction established in this study is simple,sensitive,accurate,and reproducible,which can provide a basis for the quality evaluation of Didang Qigui Decoction.

Objective:To investigate the factors contributing to frailty in very elderly patients with multimorbidity.Methods:This cross-sectional study enrolled 119 very elderly patients with multimorbidity who were hospitalized in the Department of Geriatrics of Huadong Hospital Affiliated to Fudan University from August 2022 to March 2023.The study aimed to understand the basic status of multimorbidity by collecting general information, the number and types of diseases, and frailty status.The subjects were divided into frail and non-frail groups through comprehensive geriatric assessment.Various factors including gender, age, Tinetti balance gait score, risk of sarcopenia, dementia, depression, risk of deep vein thrombosis, dysphagia, comorbidity index, medication count, Basic Activities of Daily Living(BADL)score, Instrumental Activities of Daily Living(IADL)score, Nutritional Risk Screening 2002(NRS-2002)score, Norton pressure injury risk assessment score, and Social Support Rating Scale(SSRS)score were compared.The correlation between each factor and the occurrence of frailty was analyzed using univariate analysis and multivariate Logistic regression analysis.Results:A total of 119 elderly inpatients with multimorbidity, with an average age of 90.8±5.9 years old, were included in the study.The incidence of frailty was 68.9%(82 cases).Univariate analysis revealed significant statistical differences between the frail group and the non-frail group in various factors including age( t=-3.131, P=0.002), Tinetti score( Z=-5.544, P<0.001), risk of sarcopenia( χ2=39.205, P<0.001), dysphagia( χ2=5.937, P=0.015), Charlson comorbidity index( Z=-2.565, P=0.010), medication count( Z=-3.325, P<0.001), BADL( Z=-5.871, P<0.001), IADL( Z=-5.062, P<0.001), Norton score( Z=-5.922, P<0.001), and SSRS social support( Z=-2.637, P=0.008).Multivariate logistic regression analysis showed that the Tinetti score( OR=0.843, 95% CI: 0.737-0.966, P=0.014), decreased muscle strength( OR=11.226, 95% CI: 2.157-58.432, P=0.004), sarcopenia( OR=18.084, 95% CI: 2.041-106.211, P=0.009), Norton score( OR=0.462, 95% CI: 0.254-0.838, P=0.011), and medication count( OR=1.153, 95% CI: 1.000-1.329, P=0.049)were independently associated with frailty. Conclusions:In very elderly patients with multimorbidities, the occurrence of frailty is notably increased.Frailty is linked to multiple risks including falls, muscle weakness/sarcopenia, pressure ulcer risk, and polypharmacy, and these risks are independent of other factors.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

The aquatic grass Zizania latifolia grows symbiotically with the fungus Ustilago esculenta producing swollen structures called Jiaobai, widely cultivated in China. A new disease of Z. latifolia was found in Zhejiang Province, China. Initial lesions appeared on the leaf sheaths or sometimes on the leaves near the leaf sheaths. The lesions extended along the axis of the leaf shoots and formed long brown to dark brown streaks from the leaf sheath to the leaf, causing sheath rot and death of entire leaves on young plants. The pathogen was isolated and identified as the bacterium Pantoea ananatis, based on 16S ribosomal RNA (rRNA) gene sequencing, multilocus sequence analysis (atpD (β-subunit of ATP synthase F1), gyrB (DNA gyrase subunit B), infB (translation initiation factor 2), and rpoB (β‍-subunit of RNA polymerase) genes), and pathogenicity tests. Ultrastructural observations using scanning electron microscopy revealed that the bacterial cells colonized the vascular tissues in leaf sheaths, forming biofilms on the inner surface of vessel walls, and extended between vessel elements via the perforated plates. To achieve efficient detection and diagnosis of P. ananatis, species-specific primer pairs were designed and validated by testing closely related and unrelated species and diseased tissues of Z. latifolia. This is the first report of bacterial sheath rot disease of Z. latifolia caused by P. ananatis in China.
Pantoea/genetics* ; Plant Diseases/microbiology* ; Poaceae/microbiology* ; Virulence

Objective:To investigate the role and mechanism of miR-146b in the proliferation, metastasis and apoptosis of thyroid papillary carcinoma cells.Methods:qRT-PCR was used to detect the expression of miR-146b in thyroid papillary carcinoma cells (NPA, GLAG-66, ONCNO-DG1 and B-CPAP) and normal human thyroid cell line HTori3. After B-CPAP cells were transfected with miR-146b inhibitor, the inhibition efficiency was detected by qRT-PCR, the effect of miR-146b on PTC cells proliferation was detected by MTT assay, the effect of miR-146b on PTC cells invasion was studied by Transwell assay, and the effect of miR-146b on tumor cell apoptosis was detected by flow cytometry. SiRNA-IRAK1 was transfected into B-CPAP cell line. The cell proliferation rate, migration ability and apoptosis rate were detected by MTT, cell scratch test and flow cytometry respectively. The target gene of miR-146b, interleukin-1 associated receptor kinase 1 (IRAK1) , was predicted by bioinformatics software, and the regulatory effect of miR-146b on IRAK1 was verified by double fluorescein reporter gene experiment.Results:QRT-PCR showed that the expression of miR-146b in NPA87, KAT-5, FTC-133 and B-CPAP cell lines was significantly higher than that in normal cell HTori3, especially B-CPAP ( P<0.05) . MiR-146b inhibitor transfection could significantly reduce the expression level of miR-146b in B-CPAP cells ( P<0.01) . MTT results showed that miR-146b inhibitor could inhibit the proliferation of B-CPAP cells ( P<0.05) . Flow cytometry showed that miR-146b inhibitor could promote the apoptosis of B-CPAP cells ( P<0.05) . Transwell results showed that miR-146b inhibitor could reduce the invasive ability of B-CPAP cells ( P<0.05) . After transfection with siRNA-IRAK1, the proliferation rate of B-CPAP cells increased significantly (MTT test) , the migration ability increased (cell scratch test) , and the apoptosis rate decreased significantly (flow cytometry) ( P<0.05) . The results of double luciferase reporter gene showed that irak1 was the target gene of miR-146b, and miR-146b inhibitor could significantly up regulate the expression level of irak1 protein in B-CPAP cells. Conclusion:miR-146b may play a role in promoting the proliferation and metastasis and inhibiting cell apoptosis of PTC cells by inhibiting the downstream target protein IRAK1.

Objective:To investigate the value of 95% spectral edge frequency (SEF) in identifying the depth of anesthesia in patients with schizophrenia subjected to modified electroconvulsive therapy center.Methods:A total of 195 patients with schizophrenia who received treatment in The Affiliated Kangning Hospital of Wenzhou Medical University in April to December 2020 were included in this study. They were randomly divided into three groups with 65 patients each. Three groups of patients received different doses of anesthesia before undergoing MECT as follows: group A: propofol 1.5 mg/kg, atropine 0.5 mg/kg, succinylcholine chloride 1.0 mg/kg; group B: propofol 2.0 mg/kg, atropine 0.5 mg/kg, succinylcholine chloride 1.0 mg/kg; group C: propofol 2.5 mg/kg, atropine 0.5 mg/kg, succinylcholine chloride 1.0 mg/kg. 95% SEF and bispectral index (BIS) were measured when patients were awake before treatment (T 1), when eyelash reflex disappeared (T 2), at the beginning of electrical stimulation (T 3), at 3 minutes after electrical stimulation (T 4), and when patients were completely awake (T 5) and compared between groups. The incidence of adverse reaction was recorded at 1 day after treatment. Results:At T 1-T 5, 95% SEF in the group A was (28.50 ± 0.87) Hz, (21.49 ± 0.91) Hz, (21.99 ± 0.92) Hz, (28.42 ± 1.29) Hz, (28.40 ± 1.15) Hz respectively, and it was (28.34 ± 0.91) Hz, (18.93 ± 0.86) Hz, (19.05 ± 0.83) Hz, (27.54 ± 0.73) Hz, (28.42 ± 1.21) Hz respectively in group B and (28.26 ± 0.90) Hz, (16.41 ± 0.75) Hz, (16.36 ± 0.75) Hz, (26.58 ± 0.64) Hz, (28.48 ± 1.19) Hz respectively in group C. 95% SEF measured at T 2 ( t = 24.49, 48.60, both P < 0.05), T 3 ( t = 28.47, 54.51, both P < 0.05), and T 4 ( t = 7.61, 15.91, both P < 0.05) in groups B and C were significantly lower than those in group A. 95% SEF measured at T 2 ( t = 24.11, P < 0.05), T 3 ( t = 26.04, P < 0.05) and T 4 ( t = 8.30, P < 0.05) in group C were significantly lower than those in group B. At T 1-T 5, BIS in group A was (94.16 ± 2.07), (55.34 ± 1.93), (56.61 ± 1.84), (76.29 ± 1.94) and (93.84 ± 2.39) respectively, and it was (94.51 ± 2.25), (52.39 ± 1.58), (52.45 ± 1.94), (73.58 ± 2.19), (93.28 ± 2.52) respectively in group B and (93.97 ± 2.16), (50.57 ± 1.96), (51.60 ± 2.03), (69.51 ± 2.12), (93.57 ± 2.66) respectively in group C. BIS values measured at T 2 ( t = 24.49, 48.60, both P < 0.05), T 3 ( t = 28.34, 54.28, both P < 0.05), and T 4 ( t = 7.61, 15.91, both P < 0.05) in groups B and C were significantly lower than those in group A. BIS measured at T 2 ( t = 24.11, P < 0.05), T 3 ( t = 25.93, P < 0.05), and T 4 ( t = 8.30, P < 0.05) in group C were significantly lower than those in group B. Correlation analysis showed that 95% SEF measured at T 2 ( r = 0.65, P < 0.05), T 3 ( r = 0.68, P < 0.05) and T 4 ( r = 0.49, P < 0.05) were positively correlated with BIS measured at corresponding time points. There were no significant differences in duration of electrical stimulation [(61.25 ± 4.32) seconds, (45.19 ± 3.68) seconds, and (27.54 ± 2.54) seconds, F = 1 434.14, P < 0.05], post-onset inhibition index [(87.68 ± 5.82)%, (81.59 ± 5.35)%, (75.27 ± 4.87)%, F = 87.09, P < 0.05], and average seizure energy index [(5 668.38 ± 1 264.01) μV2, (4 555.61 ± 1 058.96) μV2, (3 642.25 ± 792.68) μV2, F = 59.97, P < 0.05] among the three groups. Duration of electrical stimulation ( t = 36.07, 75.71, both P < 0.05), post-onset inhibition index ( t = 9.15, 18.66, both P < 0.05), and average seizure energy index ( t = 8.49, 15.46, both P < 0.05) in groups B and C were significantly lower than those in group A. Duration of electrical stimulation, post-onset inhibition index and average seizure energy index in group C were significantly lower than those in group B ( t = 39.64, 9.50, 6.97, all P < 0.05). BIS was positively correlated with duration of electrical stimulation ( r = 0.68, P < 0.05), post-onset inhibition index ( r = 0.55, P < 0.05) and average seizure energy index ( r = 0.42, P < 0.05). There were no significant differences in the incidences of headache, myalgia, nausea and vomiting among the three groups ( P > 0.05). Conclusion:95% SEF was positively correlated with BIS in patients with schizophrenia. BIS measured at T 2 was positively correlated with effect of modified electroconvulsive therapy center.

Objective:To investigate the efficacy of magnesium sulfate combined with labetalol on severe preeclampsia and the effects on serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular endothelial growth factor (VEGF) and pregnancy associated plasma protein-A (PAPP-A).Methods:Eighty-five patients with severe preeclampsia who received treatment in Jinhua Municipal Central Hospital between January 2019 and June 2020 were included in this study. They were randomly assigned to receive treatment either with magnesium sulfate (control group, n = 42) or magnesium sulfate combined with labetalol (observation group, n = 43). Before and after treatment, 24-hour dynamic blood pressure, 24-hour urinary protein excretion and umbilical artery hemodynamics were determined. In addition, serum levels of sICAM-1, VEGF and PAPP-A were detected. Results:After treatment, 24-hour mean arterial pressure, 24-hour urine protein excretion in the control and observation groups were significantly decreased compared with before treatment. After treatment, the 24-hour mean arterial pressure [(116.45 ± 9.63) mmHg vs. (120.74 ± 9.48) mmHg] and 24-hour urine protein excretion [(1.85 ± 0.52) g vs. (2.33 ± 0.75) g] were significantly lower than those in the control group ( t = 2.069, 3.436, both P < 0.05). The umbilical artery resistance index in the control group, and the peak systolic velocity/end-diastolic velocity ratio and the umbilical artery resistance index in the observation group were significantly decreased after treatment compared with before treatment (all P < 0.05). After treatment, the peak systolic velocity/end-diastolic velocity ratio in the observation group was significantly lower than that in the control group [(2.80 ± 0.50) vs. (3.01 ± 0.45), t = 2.034, P < 0.05]. After treatment, serum sICAM-1 and PAPP-A levels were significantly decreased, and serum VEGF level was significantly increased, in each group (all P < 0.05). After treatment, serum levels of sICAM-1 [(548.52 ± 102.74) mg/L vs. (647.52 ± 124.15) mg/L, t = 4.009, P < 0.05] and PAPP-A [(111.74 ± 28.52) U/L vs. (134.24 ± 35.96) U/L, t = 3.200, P < 0.05] in the observation group were significantly lower than those in the control group, and serum VEGF level in the observation group was significantly higher than that in the control group [(32.12 ± 7.45) ng/L vs. (28.17 ± 6.23) ng/L, t =2.659, P < 0.05]. There was no significant difference in the incidence of poor pregnancy outcome between the control and study groups ( P > 0.05). Conclusion:Magnesium sulfate combined with labetalol exhibits good therapeutic effects on severe preeclampsia. The treatment method can improve umbilical artery hemodynamics, and its mechanism may be related to its effect on vascular endothelial function.