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.

Objective To explore the implementation effects and application value of the Clinical Rehabilitation Integration Plan based on the graded management of rehabilitation treatment programs in a 3A general hospital.Methods The details of the programme were firstly formulated according to the needs of clinical rehabilitation and the implementation plan was formed,and then the integrated clinical rehabilitation work was carried out for 1 year accordingly,and finally the effects before and after the implementation of the programme were compared and analysed by selecting the indicators of departmental operation and patient satisfaction.Results The rehabilitation programme was classified into 4 levels according to the degree of technical difficulty and medical risk,and its connotation and management requirements were defined in detail.The implementation of the programme included organisational structure,training and assessment,authorisation management and quality control.The programme was carried out in 8 clinical departments in the hospital,and the overall willingness of the clinical departments to develop early rehabilitation was improved since 2022.Conclusion This program can improve the operational efficiency of clinical departments and patient prognosis.

Drug use monitoring and evaluation play a key role in promoting drugs to return to clinical value,optimizing the basic medicine system,and improving the drug supply guarantee system.In order to promote the implementation of drug use monitoring and evaluation in medical institutions,the Pharmaceutical Affairs Committee of the Chinese Hospital Association led the efforts of organizing relevant domestic experts to follow the group standard development process.It successfully formulated the group standard of Drug Use Monitoring and Evaluation through the steps of problem sorting,framework construction,evidence collection,draft writing,opinion consultation,and standard formation.This article introduces the standard formulation process in detail,and explains and analyzes the content of the standard,aiming to help readers better understand the connotation of drug use monitoring and evaluation,and provide practical guidance.

Objective To investigate the influencing factors of falls and serious falls among individuals aged 45 years and above in China,as well as explore the association between falls and multimorbidity,thereby pro-viding empirical evidence for the formulation of effective strategies to prevent falls.Methods The study utilized data from the CHARLS 2020 dataset and employed various statistical methods,including descriptive statistics,χ2 test,quadratic regression,and logistic regression.Additionally,subgroup analyses were conducted on key vari-ables.Results The prevalence of falls and serious falls among individuals aged 45 and above in China was found to be 17.42%and 6.86%,respectively.Multimorbidity emerged as a significant determinant influencing both falls and serious falls,with a higher number of diseases being associated with an increased prevalence of these events.Conclusion In order to effectively address the issue of falls in middle-aged and elderly individuals,particularly those with multimorbidity,it is imperative to integrate multimorbidity considerations into the comprehensive fall intervention process.

Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-‍1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Humans ; Carcinoma, Hepatocellular/pathology* ; Cell Hypoxia ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Liver Neoplasms/pathology* ; Signal Transduction/genetics* ; tRNA Methyltransferases/metabolism*

Objective To understand the relationship between air pollutants and digestive system cancers, and to provide a reference for future research and prevention and control of digestive system cancer. Methods All relevant literature published in English between 1970-2022 was searched through the databases of PubMed, web of science and Embase, and meta-analysis was used to explore the effects of specific air pollutants on digestive system cancers. Results PM_2.5 was able to increase the risk of incidence or mortality of total digestive cancers by 11% (1.05 to 1.17). For specific cancers, PM_2.5 was only associated with an increased risk of liver cancer in this study, with a combined RR (95% CI) of 1.31 (1.19 to 1.46), while there was no statistically significant association with other specific digestive cancers ( P>0.05）. NO2 increased the risk of incidence or mortality of total digestive cancers by 3% (1.00 to 1.07). Conclusion For specific digestive system cancers, PM_2.5 has the most pronounced effect on liver cancer. More evidence is needed to support the relationship between NO₂ and cancer. Currently, it has been observed that NO2 has a negative effect on overall digestive cancers. This study provides insights for the prevention and control of digestive system cancer in countries and regions with high PM_2.5 and NO₂ concentrations.

OBJECTIVE: To explore the clinical characteristics and molecular genetic mechanism of a fetus with recombinant chromosome 8 (Rec8) syndrome. METHODS: A fetus who was diagnosed with Rec8 syndrome at the Provincial Hospital Affiliated to Shandong First Medical University on July 20, 2021 due to high risk for sex chromosomal aneuploidy indicated by non-invasive prenatal testing (NIPT) (at 21st gestational week) was selected as the study subject. Clinical data of the fetus was collected. G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out on the amniotic fluid sample. Peripheral blood samples of the couple were also subjected to G banded karyotyping analysis. RESULTS: Prenatal ultrasonography at 23rd gestational week revealed hypertelorism, thick lips, renal pelvis separation, intrahepatic echogenic foci, and ventricular septal defect. The karyotype of amniotic fluid was 46,XX,rec(8)(qter→q22.3::p23.1→qter), and CMA was arr[GRCh37]8p23.3p23.1(158049_6793322)×1, 8q22.3q24.3(101712402_146295771)×3. The karyotype of the pregnant woman was 46,XX,inv(8)(p23.1q22.3), whilst that of her husband was normal. CONCLUSION The Rec8 syndrome in the fetus may be attributed to the pericentric inversion of chromosome 8 in its mother. Molecular testing revealed that the breakpoints of this Rec8 have differed from previously reported ones.
Humans ; Fetus/abnormalities* ; Chromosomes, Human, Pair 8 ; Female ; Pregnancy ; Karyotyping

ObjectiveTo evaluate the proficiency and consistency of domestic and foreign testing institutions in the field of veterinary drug residue detection in food， and to promote international cooperation and mutual recognition of testing results among these institutions. MethodsA robust statistical analysis was conducted on the testing results of 20 laboratories in eight countries and regions across North America， Europe， and Asia. The laboratories’ testing capabilities were evaluated using Z-score comparison. ResultsAmong the 20 participating laboratories， 18 achieved satisfactory results， resulting in a satisfaction rate of 90%， while 2 laboratories （10%） failed to meet the requirements. The satisfaction rate of domestic laboratories （100%） was higher than that of foreign laboratories （81.8%）. ConclusionDomestic laboratories perform better than overseas laboratories in determining veterinary drug residues in food. To enhance testing capabilities， these overseas laboratories with unsatisfactory evaluation results should strengthen their daily quality control and ensure traceability of original records.

This study selected the top five general hospitals in the United States of America, collected the practice information of acupuncturists through the official website, and analyzed the professional department, expertise, professional title, education background, residency, fellowship, board certification, etc. of these acupuncturists to understand the practice situation of acupuncturists in the hospitals. The results of the study showed the practice of acupuncturists in the United States of America is improving. With further localization, locally trained acupuncturists have gradually become the main body of acupuncturists; acupuncture treatment is still mainly for analgesia, but the scope of treatment continues to expand, and departments that accept acupuncturists are gradually increasing. However, the group of licensed acupuncturists is still a minority in the group of acupuncturists in the United States of America. Native American physicians still use acupuncture as an alternative option and neglect to obtain a license. The entry barrier for acupuncturists still needs to be raised.

Objective:To investigate the effects of fluoride exposure on autophagy and the expression levels of adenosine monophosphate activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Unc-51-like kinase 1 (ULK1) in mouse neuroblastoma and rat glioma fusion cells (NG108-15 cells).Methods:NG108-15 cells were cultured in vitro and divided into control group (0 mg/L), low fluoride group (20 mg/L), medium fluoride group (40 mg/L) and high fluoride group (80 mg/L) according to the final concentration of sodium fluoride, and the cells were collected after 24 h of treatment for standby. NG108-15 cells autophagy was detected by immunofluorescence/immunocytochemistry (IF/ICC method, the autophagy positive control group was treated with chloroquine phosphate); the mRNA expression levels of AMPK, mTOR and ULK1 in each group were detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR); the protein expression levels of autophagy related protein microtubule-associated protein 1 light chain 3B (LC3B), AMPK, mTOR, ULK1, phosphorylation (p)-AMPK, p-mTOR, p-ULK1 in each group were detected by Western blotting. Results:No autophagosome was detected in the control group, and autophagosomes were detected in all the fluoride groups. The protein expression level of LC3B in the low, medium and high fluoride groups (1.80 ± 0.59, 2.16 ± 0.60, 2.30 ± 0.57) was significantly higher than that in the control group (1.00 ± 0.29, P < 0.05). The results of qRT-PCR showed that compared with the control group, the mRNA expression levels of AMPK in medium and high fluoride groups were higher (2.30 ± 0.57, 4.41 ± 1.05 vs 1.00 ± 0.01, P < 0.05); the mRNA expression levels of mTOR in the low, medium and high fluoride groups were lower (0.79 ± 0.04, 0.76 ± 0.09, 0.64 ± 0.10 vs 1.00 ± 0.01, P < 0.05), and the mRNA expression levels of ULK1 were higher (1.81 ± 0.39, 1.96 ± 0.35, 4.22 ± 1.03 vs 1.00 ± 0.01, P < 0.05). The results of Western blotting showed that compared with the control group, the protein expression levels of AMPK (1.21 ± 0.05, 1.20 ± 0.04, 1.30 ± 0.07 vs 1.00 ± 0.03), p-AMPK (1.12 ± 0.05, 1.20 ± 0.06, 1.49 ± 0.07 vs 1.00 ± 0.02), ULK1 (1.16 ± 0.05, 1.26 ± 0.05, 1.15 ± 0.05 vs 1.00 ± 0.04) and p-ULK1 (1.19 ± 0.04, 1.17 ± 0.02, 1.24 ± 0.05 vs 1.00 ± 0.05) in the low, medium and high fluoride groups were higher ( P < 0.05), and the protein expression levels of mTOR were lower (0.77 ± 0.03, 0.60 ± 0.03, 0.55 ± 0.04 vs 1.00 ± 0.04, P < 0.05); the protein expression levels of p-mTOR in the medium and high fluoride groups were lower (0.93 ± 0.05, 0.48 ± 0.02 vs 1.00 ± 0.02, P < 0.05). Conclusion:Fluoride exposure can induce autophagy in NG108-15 cells, and the expression of AMPK and ULK1 are up-regulated, while the expression of mTOR is down-regulated.