Comparison of clinical medicine proficiency tests of China and Japan and the enlightenment / 中华医学教育探索杂志

The Clinical Medicine Proficiency Test developed by the National Medical Examination Center of China in 2020 aims to assess whether clinical medical students possess the necessary medical humanities and basic medical theoretical knowledge and skills required for clinical internships. Since 2002, Japan has implemented the pre-clinical clerkship objective structured clinical examination and computer-based testing, which share similarities with China's proficiency test in terms of examination objectives, content, format, and score evaluation. Through comparing the examinations of China and Japan, this article concludes that it is necessary to learn from Japan's experience to expedite the process of promoting the Clinical Medicine Proficiency Test as an industry admission examination in China. We suggest that medical schools should keep tracking the development of the proficiency test and fully leverage its role in urging students to pay more attention to clinical internships. We also urge medical schools to establish a three-level examination system based on post competency criteria in line with the standards of the National Medical Licensing Examination to improve the quality of medical education.

Clinical Research Progress of L-carnitine in the Treatment of Primary Carnitine Deficiency / 医药导报

L-carnitine is a carrier that assist in transport of long-chain fatty acids into mitochondria and an effective drug for treating primary carnitine deficiency(PCD).Starting supplementation as early as possible before irreversible organ damage oc-cured can alleviate organ damage,reduce the risk of sudden death,and improve the quality of life.However,in recent years,some studies have suggested that long-term oral L-carnitine has potential risks,the metabolism of L-carnitine through intestinal flora re-sults in the production of trimethylamine oxide(TMAO),which can increase the risk of cardiovascular disease(CVD).There-fore,this paper summarizes the clinical research progress of L-carnitine in treating PCD to provide a theoretical basis for the clini-cal application of L-carnitine in PCD.

Comparative Study on the Payment of Medical Insurance for Innovative Drugs Between China and Foreign Countries / 医药导报

Payment by diagnosis related groups(DRG)is an important research direction in China's current medical insurance payment reform.However,it limits the clinical development and utilization of innovative medicines to a certain extent.Additional payments for innovative medicines have been thoroughly studied in many countries.This paper conducted an analysis and summary of the global experience regarding additional payment for innovative medicines under the DRG payment system.U-sing the United States,France,and Germany as case studies,this paper also examined the current state of medical insurance pay-ment for innovative medicines in China and the influence of DRG payment on the development of such medicine.In addition,it has put forward explicit policy recommendations,including the establishment of inclusion criteria,the selection of appropriate payment modes,the implementation of dynamic adjustment mechanisms,the enhancement of payment methods,etc.This paper aims to provide references to comprehensively promote DRG payment reform while further establishing and enhancing medical in-surance payment mechanisms related to innovative medicines in the context of China's national conditions.

Exploration of signaling pathways with unclear action status and possible effects on related diseases or functions after knockdown of silencing information regulator 1 gene in chondrocytes / 中国组织工程研究

BACKGROUND:silencing information regulatory 1(SIRT1)regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation,thereby promoting cartilage defect repair. OBJECTIVE:To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes,as well as diseases or functions that produce changes using high-throughput technology. METHODS:ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups:the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group.GeneChip? Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection.Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors.Moreover,enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION:After knocking down the SIRT1 gene,there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes.According to the ranking of-Log(P-value),we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status,including IGFBP4,TGFBR1,CTGF,COL4A5,LHX2,IL1RL1,and KLF6.According to the ranking of-Log(P-value),there were significant changes in 14 disease or function modules,including cellular growth and proliferation,organism survival,cell death and survival.According to the number of differentially expressed genes,there were significant changes in three disease or function modules,including organismal injury and abnormalities,cancer,and cell death and survival.According to the comprehensive ranking of-Log(P-value)and the number of differentially expressed genes,the disease or function module related to intrinsic immune response was significantly activated.

Antitumor Drugs Targeting Mutant p53 Protein / 生物化学与生物物理进展

The p53 protein is an essential tumor suppressor in the human body that plays a critical role in preventing tumor formation by controlling cell cycle arrest and promoting apoptosis. Mutations in the p53 gene are frequently observed in more than 50% of tumor tissues and lead to the generation of mutant p53 proteins, which not only have a dominant-negative effect (DN) that hinders the function of wild-type p53 protein but also have gain-of-function (GOF) effects that stimulate tumor development by regulating cell metabolism, invasion, migration, and other processes. Therefore, mutant p53 protein has become a specific drug target for cancer therapy. However, the lack of a drug-binding pocket and smooth surface of mutant p53 proteins have made them undruggable targets for a long time. In recent years, with the development of high-throughput screening technology and an enhanced understanding of the structure and conformational changes exhibited by mutant p53 proteins, a multitude of small molecule compounds directed against mutant p53 protein have been identified, exhibiting substantial in vitro anti-tumor efficacy. Moreover, some of these compounds have entered clinical trials. This review summarized the direct and indirect strategies for the treatment of cancers targeting mutant p53, with a primary focus on the mechanisms of action of small molecule compounds that reactivate mutant p53 protein or degrade mutant p53 protein. The aim is to provide assistance for the development of innovative drugs targeting mutant p53 protein in the future.

Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway / 中国中药杂志

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.

Conservative treatment of supination and external rotation for type Ⅲ and Ⅳankle fracture by bone setting / 中国骨伤

OBJECTIVE@#To explore curative effect of conservative treatment of supination-lateral rotation (SER) with type Ⅲ and Ⅳ ankle fracture by bone setting technique.@*METHODS@#From January 2017 to December 2019, 64 patients diagnosed with SER with type Ⅲ and Ⅳ ankle fracture were treated with manipulative reduction and conservative treatment (manipulation group) and surgical treatment with open reduction and internal fixation (operation group), 32 patients in each group. In manipulation group, there were 17 males and 15 females, aged from 15 to 79 years old with an average of (51.42±13.68) years old;according to Lauge-Hansen classification, there were 8 patients with supination external rotation type Ⅲ and 24 patients with type Ⅳ. In operation group, there were 13 males and 19 females, aged from 18 to 76 years old with an average of (47.36±15.02) years old;7 patients with type Ⅲ and 25 patients with type Ⅳ. Displacement of ankle fracture was measured by Digimizer software, and compared before treatment, 3 and 12 months after treatment between two groups. Lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement were measured and compared between two groups. Mazur score was used to evaluate ankle joint function.@*RESULTS@#All patients were followed up from 12 to 36 months with an average of (17.16±9.36) months. There were statistical differences in lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement in manipulation group before and after reduction(P<0.05). Compared with operation group, there were no statistically significant differences in lateral malleolus shift, lateral malleolus shift, lateral malleolus contraction shift(P>0.05), while there were statistically significant differences in lateral malleolus shift, posterior malleolus shift up and down (P<0.05). Mazur scores of ankle joint at 3 months after treatment in manipulation group and operation group were 68.84±13.08 and 82.53±7.31, respectively, and had statistical differences(P<0.05), while there was no difference in evaluation of clnical effect(P>0.05). There were no differences in Mazur score and evaluation of clnical effect between two groups at 12 months after treatment (P>0.05).@*CONCLUSION@#Bone setting technique could effectively correct lateral displacement of medial malleolus, lateral displacement of medial malleolus, lateral displacement of lateral malleolus and lateral contraction displacement of lateral malleolus in supination lateral rotation type Ⅲ and Ⅳ ankle fracture, and has good long-term clinical effect, which could avoid operation for some patients and restore ankle function after fracture.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅰ): classification of processing routes / 中国中药杂志

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (Ⅱ): classification of tablets disintegration behavior / 中国中药杂志

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.

Patent application of intelligent quality control technology in traditional Chinese medicine production process: a review / 中国中药杂志

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.

Status and associated factors of pre-exposure prophylaxis use among men who have sex with men in 24 cities in China / 中华流行病学杂志

Objective: To understand the cognition and medication use of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in China and its associated factors. Method: From August 25 to September 5, 2021, 2 447 MSM were recruited in 24 cities to complete the online questionnaire through a male social interaction platform, Blued 7.5 software. The survey contents included demographic information of the respondents, PrEP awareness and usage, and risk behaviors. Descriptive analysis and multi-level logistic regression were performed for data analysis. SPSS 24.0 and SAS 9.4 software were used for statistical analysis. Results: Among the 2 447 respondents of MSM, 1 712 (69.96%) had heard of PrEP, 437 (17.86%) ever used PrEP, 274 (11.20%) were on PrEP, and 163 (6.66%) had discontinued PrEP; among the 437 cases (whoever used PrEP), more than 61.88% (388/627) adopted emtricitabine/tenofovir disoproxil fumarate regimen, and most of them adopted on-demand regimen. The average PrEP dosage reported in the past year is 1.12 tabletsper person per week. PrEP purchase was primarily via an online channel, and the most concerned factor was the PrEP effectiveness on HIV prevention. The most common reasons for discontinuing PrEP, reported by 163 cases, were the lack of HIV risk perception, the use of a condom to prevent HIV, and the economic burden of PrEP use. The logistic regression analysis showed that PrEP use among MSM in 24 cities was statistically associated with age, monthly income, ever having unprotected anal sex in the past year, used sexual drugs and sexually transmitted disease (STD) diagnosis in the past year. Compared with MSM aged 18-24, the proportion of MSM was relatively lower among those aged 25-44, who discontinued the PrEP (aOR=0.54,95%CI:0.34-0.87) or never used PrEP (aOR=0.62,95%CI:0.44-0.87). The proportion of unprotected anal sex among MSM currently on PrEP use was higher than those who have stopped PrEP and never used PrEP (all P<0.05). Those MSM group, with monthly income higher than 5 000 Yuan, used sexual drugs and STD diagnosis in the past year were more likely to have a higher rate for PrEP usage (all P<0.05). Conclusions: Currently, pre-exposure prophylaxis in the MSM group is primarily obtained via the online channel and adopted in an on-demand mode. Although the PrEP users have reached a certain proportion, it is still necessary to strengthen health education on the PrEP effects and side effects of MSM and to improve the awareness and use rate, especially for young MSM group, which can be combined with the advantages of the internet targeting its needs and use barriers.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅲ): classification of granule dissolving behaviors / 中国中药杂志

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(β-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly β-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

Risk identification and prevention and control for medical insurance fund utilization based on fault tree analysis / 中华医院管理杂志

Strengthening the supervision of medical insurance funds is an important measure to promote the healthy and sustainable development of the medical security system. In January 2022, a tertiary general hospital in Beijing carried out risk identification and prevention and control practices for the use of medical insurance funds. By using such methods as fault tree analysis and risk matrix, the probability and impact of events were quantitatively evaluated, high-risk events during the use of medical insurance funds were identified, and corresponding risk prevention and control measures were developed, relying on intelligent regulatory systems. From January to November 2022, the hospital outpatient medical insurance refusal amount(20 080 yuan) caused by such high-risk events as exceeding drug instructions, exceeding medical insurance indications, and exceeding age limits decreased by 42.30% compared to the same period in 2021(11 585 yuan). The discharge and settlement time of medical insurance patients decreased from 3 working days to 1 working day. This practice had effectively improved the quality and efficiency of hospital medical insurance fund supervision, improved patients′ medical experience, and provided reference for strengthening the safe and standardized use of medical insurance funds by medical institutions.

Expression of nicotinamide -N- methyltransferase in various tumor tissues and its prognostic value in papillary thyroid carcinoma / 肿瘤研究与临床

Objective:To investigate the expression of nicotinamide-N-methyltransferase (NNMT) in various tumor tissues and its prognostic value in papillary thyroid carcinoma.Methods:The paraffin samples of surgically resected tissues from 168 cases of colorectal cancer, 75 cases of gastric cancer, 178 cases of lung cancer, 15 cases of liver cancer, 60 cases of thyroid cancer, 7 cases of prostate cancer, 74 cases of breast cancer, and 14 cases of renal cancer were collected from Sir Run Run Show Hospital, Zhejiang University School of Medicine and the Third Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine between January 2016 and December 2021; tissue samples of 58 cases of papillary thyroid cancer and another 19 cases of thyroiditis were collected between January 2016 and December 2016. Immunohistochemistry kits were prepared and performance tests were performed. Normal specimens (>5 cm from the margin of paracancerous tissues) and the samples of gastric cancer, colorectal cancer, lung cancer, thyroid cancer, prostate cancer, breast cancer, and kidney cancer tissues as well as their paracancerous tissues (3 cm from the tumor edge) were selected. Immunohistochemistry kits were used to detect the expression of NNMT protein in normal tissue samples, different tumor tissues and their paracancerous tissues. X-tile software combined with the receiver operating characteristics curve of NNMT in the diagnosis of tumor tissues and paracancerous tissues in papillary throid carcinoma were used to determine the optimal cut-off value (41.5); < 41.5 was treated as the NNMT protein low expression group and ≥ 41.5 was treated as the NNMT protein high expression group. The expression of NNMT protein in patients with papillary thyroid carcinoma with different clinicopathological characteristics was compared; Kaplan-Meier method was used to analyze the overall survival of the patients with papillary thyroid carcinoma; Cox proportional risk model was used to conduct multivariate analysis on the influencing factors of overall survival.Results:The prepared immunohistochemistry kits were valid for at least 12 months, with good intra-batch and batch-to-batch repeatability, good stability and specificity. NNMT protein was not or occasionally lowly expressed in colorectal, lung, thyroid, prostate, breast, kidney, and gastric tissues. NNMT protein was highly expressed in colorectal cancer, gastric cancer, breast cancer, kidney cancer, thyroid cancer, lung cancer, prostate cancer tissues, while lowly expressed in colorectal cancer, gastric cancer, breast cancer, kidney cancer, thyroid cancer, lung cancer, prostate cancer adjacent tissues. The high expression rates of NNMT protein in thyroiditis tissue, papillary thyroid cancer tumor tissue and paracancerous tissues were 15.79% (3/19), 68.97% (40/58) and 31.03% (18/58), respectively, and the high expression rate of NNMT protein in papillary thyroid carcinoma tissue was higher than that in thyroiditis tissue and paracancerous tissue. All patients with papillary thyroid cancer were divided into the NNMT protein high expression group (40 cases) and the low expression group (18 cases). There were no statistically significant differences in NNMT protein expression among patients with different age, gender, degree of differentiation, lump diameter, TNM stage, lymph node metastasis, and serum anti-thyroglobulin antibody (TgAb) level (all P > 0.05). The median overall survival time of 58 patients was 18.5 months, and the 5-year overall survival rate was 90.0%. The overall survival of patients with a lump diameter of ≥2 cm was worse than that of those with a lump diameter of < 2 cm ( P < 0.001), and the overall survival of patients with lymph node metastasis was worse than that of those without lymph node metastasis ( P = 0.041). The overall survival of patients in the NNMT protein high expression group was worse than that of those in the NNMT protein low expression group, and the overall survival of patients with high serum TgAb level was worse than that of those with low serum TgAb level, while the differences were not statistically significant (all P >0.05). Lump diameter ( HR = 35.56, 95% CI 2.64-478.25, P = 0.007), NNMT protein expression ( HR = 308.12, 95% CI 2.21-42 958.20, P = 0.023), serum TgAb level ( HR = 142.85, 95% CI 1.88-10 854.25, P = 0.025) were independent influencing factors for the OS of patients with papillary thyroid carcinoma. Conclusions:NNMT is highly expressed in various tumor tissues. NNMT expression is related to the prognosis of patients with papillary thyroid carcinoma;the patients with high expression of NNMT have worse prognosis compared with those with low expression of NNMT.

Application of LEARNS model based on Triangle stratified model on the management of out-patients with type 2 diabetes mellitus / 中国实用护理杂志

Objective:To analyze the effects of stratified follow-up intervention combined with LEARNS model on self-management, glucose metabolism, compliance and satisfaction in patients with type 2 diabetes mellitus (T2DM).Methods:This study was a quasi-experimental study. A total of 212 patients with T2DM who visited the DM nursing clinic of Beijing Tiantan Hospital, Capital Medical University from June 2020 to May 2021 were selected and divided into control group (102 cases) and intervention group (110 cases) according to the treatment time. All the patients received the conventional medical treatment and health education guidance for 6 months, at the same time, the intervention group received management of the triangle stratified model combined with LEARNS mode. The glucose metabolism, self-management behavior, satisfaction and compliance were compared before and after the intervention.Results:Before the intervention, the baseline data of the 2 groups had no significant difference(all P>0.05) and were comparable. Three and six months after the intervention, the HbA1c values of the intervention group were (6.18 ± 0.57)% and (6.40 ± 0.47)%, which were significant better than those in the control group, (6.74 ± 0.90)% and (6.99 ± 0.91)%, the differences were significant ( t=8.05 and 9.12, both P<0.01). Three and six months after the intervention, the SDASC values in the intervention group were (46.51 ± 5.80) and (44.41 ± 5.61), which were higher than those in the control group, (43.45 ± 4.20) and (42.08 ± 3.67), the difference were significant ( t=6.56 and 5.32, both P<0.01). Three and six months after the intervention, the compliance and patient satisfaction of intervention group were better than those in the control group ( χ2=5.52 and 7.26, t=7.02 and 15.75, all P<0.05). Conclusions:Triangle hierarchical management combined with LEARNS model can effectively improve the blood glucose levels of T2DM patients as well as their self-management levels, satisfaction and compliance, which can help nurses reasonably allocate follow-up time.

Exploring risk factors for combined coronary microvascular dysfunction in patients with ischemia and non-obstructive coronary artery disease / 中华核医学与分子影像杂志

Objective:To investigate the risk factors for combined coronary microvascular dysfunction (CMD) in patients with ischemia and non-obstructive coronary artery disease (INOCA).Methods:From October 2020 to May 2022, 100 INOCA patients with myocardial ischemic symptoms who underwent coronary angiography (CAG) suggestive of <50% stenosis in all three coronary arteries at the Tenth People′s Hospital of Tongji University were prospectively recruited. Myocardial perfusion imaging (MPI), transthoracic echocardiography and cadmium-zinc-telluride (CZT) SPECT coronary flow quantification were performed in the same month, and 93 INOCA patients (36 males and 57 females, age (63.0±10.9) years) were finally included. CMD was defined as coronary flow reserve (CFR)<2.5. Independent-sample t test, Mann-Whitney U test and χ2 test were used to compare MPI results and left ventricular volume parameters between CMD and non-CMD groups. ROC curve analysis was used to analyze the efficacy of each index in predicting CMD, and independent risk factors for CMD were screened by multivariate logistic regression analysis. Results:Among 93 INOCA patients, 29 were in the CMD group and 64 were in the non-CMD group. The age, proportion of hypertension, left ventricular mass index (LVMI), summed stress score (SSS), summed difference score (SDS), left ventricular internal diameter systolic (LVIDS), interventricular septum thickness (IVST), and left ventricular posterior wall thickness (LVPWT) in the CMD group were higher than those in the non-CMD group ( t values: 2.42-3.76, χ2=8.94, z values: -3.31, -3.41, all P<0.05). ROC curve analysis showed that LVMI, SSS, SDS, LVPWT, IVST and age were significant in predicting CMD (AUCs: 0.67-0.72). Multivariate logistic regression analysis showed that LVMI (odds ratio ( OR)=1.08, 95% CI: 1.01-1.17), SDS ( OR=5.37, 95% CI: 1.95-14.78), hypertension ( OR=5.68, 95% CI: 1.34-24.18) and age ( OR=1.10, 95% CI: 1.03-1.18) were risk factors for CMD. Conclusion:LVMI, SDS, hypertension and age are strongly associated with combined CMD in INOCA patients, which can be used for early risk stratification of INOCA patients.

Efficacy of the enhanced recovery after surgery approach in endometrial cancer patients treated with surgical staging and its influence on the oxidative stress response / 中华老年医学杂志

Objective:To analyze the efficacy of the enhanced recovery after surgery(ERAS)approach in endometrial cancer patients treated with surgical staging and its beneficial effects on the oxidative stress response.Methods:Eight-two endometrial cancer patients treated with surgical staging at our hospital between March 2020 and March 2022 were recruited and divided into different groups using a computer-generated random number table, with 41 in the control group who were given routine intervention and 41 in the observation group receiving ERAS.Results:About perioperative performances, the oxidative stress response, inflammatory factor levels and complications were compared between the two groups.Results in the observation group, the intraoperative body surface temperature was higher than in the control group[(36.71±0.22)℃ vs.(36.20±0.21)℃, t=10.737, P=0.000], and the time from the end of surgery to first water intake[(4.41±1.30)h vs.(6.79±1.28)h, t=8.353, P=0.000], to first food intake[(7.86±1.35)h vs.(12.88±2.57)h, t=11.073, P=0.000], to first ambulation[(12.92±3.11)h vs.(24.24±5.06)h, t=12.204, P=0.000], to first flatus[(24.11±4.96)h vs.(35.13±6.20)h, t=8.887, P=0.000], to first bowel movement[(2.67±0.63)d vs.(4.03±1.15)d, t=6.641, P=0.000]and the length of hospitalization[(3.31±1.25)d vs.(5.77±1.59)d, t=7.788, P=0.000]were shorter than in the control group.On the third day after surgery, the levels of malondialdehyde[(77.96±7.62)μmol/L vs.(90.16±7.88)μmol/L, t=7.126, P=0.000], advanced oxidation protein products[(33.16±4.75)μmol/L vs.(43.55±5.37)μmol/L, t=9.280, P=0.000], CAT[(22.59±3.01)U/ml vs.(25.12±3.3)U/ml, t=3.609, P=0.000]and reactive oxygen species[(74.13±5.02)pmol/L vs.(90.33±5.89)pmol/L, t=13.404, P=0.000]in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same time points after surgery.On the 3rd day after surgery, the levels of Tumor Necrosis Factor-α, C-reactive protein and interleukin 6 in the two groups were higher than those on the day before surgery, but were lower in the observation group than in the control group at the same points after surgery(all P<0.05). In the observation group, the incidence of complications was 14.63%, lower than 39.02% in the control group( χ2=6.212, P=0.013). Conclusions:The ERAS approach can achieve significant results in endometrial cancer patients treated with surgical staging.It can not only improve perioperative performance, relieve oxidative stress and lower inflammatory factor levels, but also effectively prevent complications.

corilagin protects non-alcoholic fatty liver disease in mice induced by high fat and high sugar diet via regulating AMPK-autophagy signaling / 中国药理学通报

Aim To explore the effects of corilagin on non-alcoholic fatty liver disease induced by high-fat and high-sugar diet in mice via regulating AMPK-autophagy signaling. Methods Healthy 8-week-old male C57BL/6J mice were randomly divided into control group, model group and corilagin group. The mice of model group and corilagin group were fed with a high-fat and high-sugar diet for four weeks at the age of eight weeks. The corilagin group mice were also intraperitoneally injected with corilagin (20 mg • k g

In vitro transcribed (IVT) mRNA drugs: technical progress and application prospect / 药学学报

The in vitro transcribed (IVT) mRNA technology has progressed rapidly and the application of mRNA vaccines in the COVID-19 pandemic made it become the most talked-about topic. Compared with protein drugs, IVT mRNA has a lower cost; it can be modular produced and its sequence can be modified easily, so it has a broad application prospect. However, due to its short history, mRNA drugs face the problem of lacking sufficient clinical data, and there is no quality control standard for mRNA drugs except mRNA vaccines. We overview the sequence design, delivery vectors, administration, application prospect and safety considerations of mRNA drugs. We also discussed the quality control of mRNA drugs briefly.

Functional outcomes of 100 patients with adenocarcinoma of the esophagogastric junction undergoing Cheng's GIRAFFE(®) reconstruction after proximal gastrectomy / 中华胃肠外科杂志

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.