Kinase modulators approved by FDA in 2022 / 药学学报

The FDA approved a total of 37 new drugs in 2022, including 22 new molecular entities and 15 new biological products. This is the year with the lowest number of new drugs approved by the FDA since 2017. Among these approved drugs, 21 new drugs belong to the "first-in-class" category, accounting for 56% of the total approved drugs, which is the highest ratio in the past 10 years. Among the drugs approved in 2022, there are 5 small molecule kinase modulators, including the tyrosine kinase 2 (TYK2) allosteric inhibitor deucravacitinib, the first oral pyruvate kinase (PK) activator mitapivat, the Janus kinase 1 (JAK1) selective inhibitor abcrocitinib, the JAK2 selective inhibitor pacritinib and the broad-spectrum fibroblast growth factor receptor (FGFR) inhibitor futibatinib. This review briefly describes the discovery background, research and development process, synthesis routes and clinical efficacy and safety of small molecule kinase modulators approved by the FDA in 2022, hoping to provide ideas and methods for further research on kinase modulators.

The efficacy and safety of Bruton tyrosine kinase inhibitors as monotherapy in the treatment of newly diagnosed patients with Waldenström macroglobulinemia / 中华血液学杂志

Objective: To investigate the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKi) ibrutinib or zanubrutinib monotherapy in newly diagnosed patients with Waldenström macroglobulinemia (WM) . Methods: The efficacy and adverse effects of 58 patients with newly diagnosed WM receiving BTKi monotherapy in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were analyzed retrospectively from January 2018 to August 2022. Results: The response of 55 patients may be examined. Forty patients received ibrutinib monotherapy for a median of 15 months, with an overall response rate (ORR) of 85%, a main remission rate (MRR) of 70%, and a very good partial remission (VGPR) rate of 10%. Fifteen patients received zanubrutinib monotherapy for a median of 13 months, with an ORR of 93%, an MRR of 73%, and a VGPR rate of 0%. For various reasons, 10 patients were converted from ibrutinib to zanubrutinib. Ibrutinib treatment lasted an average of 7.5 months before conversion. The median duration of zanubrutinib therapy after conversion was 3.5 months. The ORRs before and after conversion were 90% and 100%, MRRs were 80% and 80%, and VGPR rates were 10% and 50%, respectively. After a median of 16 months, the 24-month progression-free survival (PFS) rate of patients who received both BTKi was 86%. PFS did not differ statistically across individuals with low, medium, and high-risk ISS scores (P=0.998). All of the patients survived. The most common side effects of BTKi were neutropenia and thrombocytopenia, which occurred in 12% and 10% of all patients, respectively. Ibrutinib accounts for 5% of atrial fibrillation, and zanubrutinib has a 7% risk of bleeding. Conclusions: In treating WM, ibrutinib or zanubrutinib provides good efficacy and tolerable adverse effects.

Role of circTmeff-1 in morphine addiction memory of mice / 中国药理学与毒理学杂志

In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.

Downward referral willingness of rehabilitation patients in an urban medical group and its influencing factors / 中国康复理论与实践

ObjectiveTo investigate the willingness of rehabilitation patients within an urban medical group to accept downward referrals and analyze the influencing factors. MethodsFrom June to October, 2023, a survey was conducted using a simple random sampling method among neurological and orthopedic rehabilitation patients in hospitals within a specific urban medical group. The 2013 version of the Andersen Model was employed to construct a theoretical framework for the willingness of rehabilitation patients to accept downward referrals and influencing factors. Within this framework, a questionnaire was designed using a 5-point Likert scale, comprising three sections including personal characteristics, environmental features and healthcare service utilization choices, totaling 23 questions. A preliminary survey was conducted, and the questionnaire had underwent reliability and validity testing. ResultsA total of 350 questionnaires were collected, with 314 valid questionnaires. The willingness of rehabilitation patients to accept downward referrals was found to be associated with age, rehabilitation specialties, rehabilitation phases, previous experiences with downward referrals, awareness of and perceptions regarding bidirectional referral policies, and understanding and opinions about the urban medical group (χ2 > 7.755, P < 0.05). The primary influencing factors were rehabilitation specialties, rehabilitation phases, previous experiences with downward referrals and perceptions of the necessity of bidirectional referral policies (P < 0.05). ConclusionRehabilitation specialties, rehabilitation phases, previous experiences with downward referrals and perceptions of the necessity of bidirectional referral policies are the primary factors that influenced the willingness of rehabilitation patients to accept downward referrals. We should formulate targeted and focused improvement measures based on the specific circumstances and key influencing factors of rehabilitation patients within the urban medical group regarding their willingness to accept downward referrals. Continuously enhancing the proportion of patients willingness to accept downward referrals is essential for the effective implementation of bidirectional referral for rehabilitation patients.

Current situation of health checkup and the management willingness of post-test abnormal values among residents of mega communities / 中华健康管理学杂志

Objective:To investigate the current status of health checkups and the management willingness of post-test abnormal values in residents of mega communities, and to explore the factors affecting the demand for health management of abnormal values after examination.Methods:A cross-sectional study. The residents of Huaguoyuan Community in Guiyang City were enrolled as the objects of this surveywith stratified systematic sampling method and questionnaire survey. The binary logistic regression was used to analyze the influencing factors of health management demand for abnormal values after examination.Results:There were 404 residents participating in this survey, and 182 cases were male (45.05%) and 222 cases were female (54.95%); the mean age was (39.64±15.03) years. There were 179 (44.31%) urban residents and 225 (55.69%) rural residents. There were 162 (40.10%) floating population and 242 (59.90%) non-floating population. Of the residents, 34.2% participated in the physical examination independently due to physical reasons. The age ( χ 2=16.227), household registration ( χ 2=16.117) and occupation ( χ 2=36.454) had statistically significant differences in residents′ participation in physical examination; the household registration ( χ 2=18.726, P<0.001) and occupation ( χ 2=18.094, P=0.034) had significant differences in the handling methods of abnormal values of physical examination. The age ( OR=7.00, P=0.032) and income ( OR=0.33, P=0.047) were the influencing factors of health management needs of abnormal values after health checkup. Conclusion:The awareness of active physical examination of residents in mega community is weak, and it is recommended to strengthen health education and health promotion; residents have a high willingness to the management of abnormal values after health checkup, it can be an important supplement to improve the service quality of physical examination related institutions.

Cost-effectiveness analysis of serplulimab combined with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of serplulimab combined with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma from the perspective of the Chinese healthcare system. METHODS A partitioned survival model with three health states was constructed for cost-effectiveness analysis. Clinical data were extracted from ASTRUM- 007. Information on parameters such as cost and health utility was derived from related websites and published literature. The quality-adjusted life years （QALYs） was used as the output index to calculate the incremental cost-effectiveness ratio （ICER）， and then compared with three times the per capita gross domestic product （GDP） in China to judge whether it was cost-effective. One- way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model； the cost- effectiveness of applying this plan to subgroup patients with programmed cell death-ligand 1 combined positive score （PD-L1 CPS） ≥10 and the scheme in the context of charitable drug donations was explored. RESULTS Among advanced or metastatic oesophageal squamous cell carcinoma patients and patients with PD-L1 CPS ≥10， serplulimab combined with chemotherapy could improve health outcomes with an augmentation of cost， compared with placebo combined with chemotherapy，resulting the ICERs were 599 623.64 yuan/QALY and 629 121.57 yuan/QALY， respectively. Therefore， serplulimab combined with chemotherapy was not cost-effective. Sensitivity analysis of single factor showed that the costs of serplulimab were the crucial factor affecting the ICER； probabilistic sensitivity analysis demonstrated basic analysis results were relatively robust. The results of scenario analysis showed that when all patients met the requirements of the charitable drug donation program， serplulimab combined with chemotherapy was cost-effective； the economic outcome of this scheme was reversed compared with the results of the basic analysis. CONCLUSIONS From Chinese healthcare perspective， first-line treatment with serplulimab in combination with chemotherapy is not a cost-effective option for patients with advanced esophageal squamous cell carcinoma， but it may be an economic option to implement a charitable drug donation program for all patients or if the price of serplulimab is significantly reduced.

Study on emergency management mechanism of drug volume-based procurement / 中国药房

OBJECTIVE To provide reference for the normalization of drug volume-based procurement （hereinafter referred to as “VBP”） and the establishment of local emergency management mechanism. METHODS Based on the equilibrium theory of the whole process of emergency management with Chinese conditions， referring to the “6+1” stage model， the emergency management mechanism of VBP was constructed； 21 provincial-level procurement projects in China from 2019 to 2022 were evaluated accordingly. RESULTS The emergency management mechanism of VBP including 14 measures in 7 stages of preparation， prevention， mitigation， response， recovery， learning and monitoring was successfully constructed. The total score of the 21 provincial-level procurement projects was 3 to 11 points， and the average score of each project in the past 4 years fluctuated slightly within 6 to 7 points. Among the 5 evaluated stages， the scores of the prevention and response stage were relatively high， followed by the mitigation and preparation stage， and the lowest in the recovery stage. Among the 11 rated emergency management measures， more than half had an average score greater than 0.5， but the average score of “determining alternative enterprise selection methods” was only 0.19. CONCLUSIONS Some emergency management measures of drug VBP are lacking， and the emergency management mechanism still needs to be perfected， which is not conducive to the development of emergency management work. The procurement organizer should focus on building a complete emergency management mechanism covering all stages， and clarify the specific measures at each stage， so as to ensure procurement effective and good in operation.

Study on the mechanism of Tanhuo Prescription in the regulation of M1-type microglia activation and reducing the damage of brain tissue in rats with cerebral ischemia / 国际中医中药杂志

Objective:To observe the effect and mechanism of Tanhuo Prescription on regulating the activation of M1 microglia and alleviating brain tissue injury in rats with cerebral ischemia.Methods:Male SD rats were divided into sham-operation group, model group, Tanhuo Prescription high-(3.68 g/kg), medium-(1.84 g/kg), low-dosage(0.92 g/kg) groups, and ginaton group (0.06 g/kg) using random number table method. Except for the sham-operation group, the other groups established cerebral ischemia rat models using the middle cerebral artery occlusion method. The balance beam walking test was used to evaluate the symptoms of neurological deficit. MRI-T2 mapping was used to measure the damage to brain tissue. LFB staining was used to observe the damage to nerve fibers. HE staining was used to observe the damage to nerve cell, and Iba-1 and CD16/Iba-1 immunofluorescence staining were used to observe the condition of microglial activation.Results:Compared with the model group, the scores of balance beam walking ability of rats in Tanhuo Prescription high-dose group and ginaton group at 24 h, 48 h and 72 h after ischemia were significantly improved ( P<0.05, P<0.01). The scores of balance beam walking ability of rats in Tanhuo Prescription low- and medium- dose groups at 72 h after ischemia were improved ( P<0.01). Compared with the model group, the T2 values of the cortex and striatum around the infarct of rats in Tanhuo Prescription high-dose group and ginaton group were significantly reduced ( P<0.05, P<0.01), and the T2 values of the striatum around the infarct of rats in Tanhuo Prescription low- and medium- dose groups were significantly reduced ( P<0.05). Compared with the model group, the LFB IOD of the cortex, striatum and outer capsule around the infarct decreased in the Tanhuo Prescription high-,low-dose group and ginaton group ( P<0.01). The LFB IOD of striatum around infarct decreased in medium- dose Tanhuo Prescription group ( P<0.01). Compared with the model group, the pathological injury degree of the striatum around the infarct of rats in Tanhuo Prescription low- ,medium-, and high-dose groups decreased, and the cell density decreased ( P<0.05, P<0.01). The density of the cortical and striatum cells around the infarct of rats in ginaton group increased ( P<0.01, P<0.05). Compared with the model group, the number of Iba-1 and CD16/Iba-1 positive cells in the cortex and striatum around the infarct decreased in Tanhuo Prescription medium-, high-dose and ginaton groups ( P<0.01). The number of CD16/Iba-1 positive cells in the cortex and striatum around the infarct of rats in Tanhuo Prescription low-dose group decreased ( P<0.01), and the number of Iba-1 positive cells in the striatum around the infarct of rats in Tanhuo Prescription low-dose group decreased ( P<0.01). Conclusion:Tanhuo Prescription can improve the symptoms of neurological deficits in rats with cerebral ischemia, reduce the neuropathological damage in the cerebral area around ischemic infarction, and inhibit the activation of M1 microglia.

Practice and effect of construction of rational drug use mode of PIVAS by the activities of quality control circle / 药学实践杂志

Objective To establish a rational drug use model of PIVAS and promote the rational drug use in clinical practices by enhancing the quality of prescription review by pharmacists. Methods The PIVAS physician orders received from 2014 to 2021 were extracted through the hospital information management (HIS) system. The types of irrational physician orders were statistically analyzed, the improvements were made by the method of quality control circle (QCC). Results The model of PIVAS rational drug use formed a standardized process. The proficiency of physician order review was improved. From 2014 to 2021, the number and proportion of unreasonable physician orders in PIVAS decreased year by year. Every type of unreasonable physician orders was improved year by year. Conclusion The professional and technical levels of pharmacist for physician order review at our hospital were improved by the model of PIVAS rational drug use. The quality of pharmaceutical service was significantly improved which ensured the safety of patients' medication.

Radiomics-based prediction of microsatellite instability in stage Ⅱ and Ⅲ rectal cancer patients based on T2WI MRI and diffusion-weighted imaging / 中华外科杂志

Objective: To examine the radiomics model based on high-resolution T2WI and diffusion weighted imaging (DWI) in predicting microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer. Methods: From February 2016 to October 2020, 175 patients with stage Ⅱ and Ⅲ rectal cancer who met the inclusion criteria were retrospectively collected. There were 119 males and 56 females, aged (63.9±9.4) years (range: 37 to 85 years), including 152 patients with microsatellite stability and 23 patients with microsatellite instability. All patients were randomly divided into the training group (n=123) and the validation group (n=52) with a ratio of 7∶3. The region of interest was labeled on the T2WI and DWI images of each patient using the ITK-SNAP software, and PyRadiomics was used to extract seven kinds of radiomics features. After removing redundant features and normalizing features, the least absolute shrinkage and selection operation were used for feature selection. One clinical model, three radiomics models and one clinical-radiomics model were constructed in the training group based on a support vector machine. The area under receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were used to evaluate the performance of the models in the verification group. Results: Three clinical features (age, degree of tumor differentiation, and distance from the lower edge of the tumor to the anal edge) and six radiomics features (two DWI-related features and four T2WI-related features) most related to microsatellite status of rectal cancer patients were selected. The AUC of the clinical-radiomics model in the training group was 0.95. In the validation group, the AUC was 0.81, better than the clinical model (0.68, Z=0.71, P=0.04), and equivalent to the T2WI+DWI model (0.82, Z=0.21, P=0.83). Conclusions: Radiomic features based on preoperative T2WI and DWI were related to microsatellite stability in patients with stage Ⅱ and Ⅲ rectal cancer and showed a high classification efficiency. The model based on the features provided a noninvasive and convenient tool for preoperative determination of microsatellite stability in rectal cancer patients.

Drug resistance and molecular typing of diarrheagenic escherichia coli from the diarrhea clinics in Qingpu District, Shanghai / 中华预防医学杂志

Objective: To analyze the drug resistance and multilocus sequence typing of five types of diarrheagenic Escherichia coli (DEC) isolated from diarrhea outpatients of diarrhea comprehensive monitoring designated hospital in Qingpu District, Shanghai from 2015 to 2019. Methods: From January 2015 to December 2019, five types of DEC, isolated and identified from diarrhea outpatient cases' anal swabs of the Qingpu branch of Zhongshan Hospital were collected to determine the minimal inhibitory concentration by using the micro broth dilution susceptibility test. The strains, resistant to the third-generation cephalosporins or carbapenems, or producing ESBLs, were selected based on the results of sensitivity tests and determined by WGS. The MLST typing of DEC was analyzed based on the WGS technology and the minimum spanning tree was constructed by BioNumerics 7.6 software to analyze the local dominant flora. Results: A total of 513 strains of DEC were detected and isolated from 4 494 anal swabs, with a detection rate of 11.42%. About 500 strains were tested for drug sensitivity to nine antibiotics in four classes, including 330 strains of enterotoxigenic E.coli (ETEC), 72 strains of enteroaggregative E.coli (EAEC), 95 strains of enteropathogenic E.coli (EPEC), 1 strain of enterohemorrhagic E.coli (EHEC), and 2 strains of enteroinvasive E.coli (EIEC). From 2015 to 2019, the resistance rate of cefotaxime-clavulanic acid was significantly different (P<0.05). The resistance rate of virulence types of DEC to nalixic acid was significantly different (P<0.05). About 71 strains of DEC were determined by WGS, and 77 drug-resistant genes were detected. Strains were classified into 32 ST subtypes, with the dominant genotypes being ST-1491 (29.6%, 21/71) and ST-10 Complex (23.9%, 17/71). All ST-1491 produced ESBLs, which were blaCTX-M gene mutant strains. The dominant type of ST-10 complex was ST-218 (35.3%, 6/17). In addition, 8 strains of EAEC, 14 strains of EPEC and 49 strains of ETEC were classified into 7, 14 and 18 ST subtypes, respectively. Conclusion: The drug resistance of DEC strains from the diarrhea outpatient case of Qingpu District is serious. The ST types of EAEC and EPEC are highly polymorphic. The dominant ST types of DEC are basically consistent with the common genotypes in southeast China.

Analysis and thinking on the practice of local regional drug online procurement in China / 中国药房

OBJECTIVE To systemically sort out the main practices of local drug online procurement， so as to provide reference for national and local governments to improve drug online procurement policies and drug price formation mechanism. METHODS By searching the official websites of 31 provincial medical security bureaus and drug-centralized procurement platforms in China， the classification methods and main goals of local drug online procurement were summarized， then the main practices of local drug online procurement were analyzed based on the main goals， and corresponding suggestion was put forward. RESULTS & CONCLUSIONS There were two classification methods of online drug procurement in each province， one is based on online or purchase methods， and the other is based on drug dimensions. Five main objectives of online drug procurement in each province are to ensure reasonable drug prices， meet clinical drug demand， ensure stable drug supply， cooperate with the implementation of drug policies， and standardize the behavior of transaction subjects. In order to achieve the five goals， each province has taken some targeted measures， but the severity of the policy varies greatly. In order to further improve the online drug procurement policy and improve the market-oriented online drug price formation mechanism， it is suggested to build the top-level design of online drug procurement， strengthen the management of the price comparison relationship of similar drugs， give full play to the monitoring function of the drug-centralized procurement platform and establish a national unified drug-centralized procurement platform.

Fortify clinical advantages and promote innovative development: comparison of the Chinese Colorectal Cancer Surgery Database with foreign databases / 中华外科杂志

With the continuous development of evidence-based medicine, increasing attention has been paid to the construction of a large medical database to ensure a source of high quality real-world data. The Chinese Medical Association Colorectal Surgery Group created the Chinese Colorectal Cancer Surgery Database (CCCD), whose objective is to promote the development of colorectal surgery and improve patient prognosis with evidence-based medicine theory. Compared to major databases around the world, CCCD contains more comprehensive information on colorectal cancer surgical cases, recording the main epidemiological characteristics and detailed surgical information, but perioperative treatment data still need to be strengthened. It is necessary to continuously expand the coverage, enrich perioperative data and strengthen data, quality control. In the future, CCCD is expected to play a role in promoting homogenization of medical services, promoting smooth and effective graded diagnosis and treatment, giving full role to the characteristics of each center to achieve integrated development, and connecting real-world data and artificial intelligence.

Impact of different lifestyle indexes on serum uric acid levels in young and middle-aged men / 中华内分泌代谢杂志

Objective:To investigate the impact of lifestyle index (LSI) on serum uric acid levels in young and middle-aged men.Methods:This was a cross sectional study. A total of 8 067 subjects underwent check-up in Taihu Sanatorium of Jiangsu Province from March 2020 to June 2021 were enrolled, average age were(46.46±8.81) years. According to age, subjects were divided into young male group (18-44 years old, n=3 269) and middle-aged male group (45-60 years old, n=4 798). Height, weight, body mass index, alcohol drinking, smoking, diet, exercise, fasting blood glucose, total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol(LDL-C), serum uric acid and other data in all cases were measured and recorded. Results:The serum uric acid level in allsubjects was (376.80±74.43)μmol/L and the prevalence of hyperuricemia was 25.7%.The serum uric acid level in the young male group was higher than that in the middle-aged male group [(381.86±74.32)μmol/L vs (373.34±74.32)μmol/L, P<0.001]. The prevalence of hyperuricemia in the young male group was higher than that in the middle-aged male group (27.4% vs 24.5%), and the difference was statistically significant ( P<0.001). With the improvement of LSI scores, the serum uric acid levels in young and middle-aged men showed a decreasing trend ( P<0.01). Logistic regression analysis showed that after adjusting for age, fasting blood glucose, total cholesterol, triglyceride, HDL-C, LDL-C, hypertension, and diabetes, LSI was an independent factor for serum uric acid levels in young and middle-aged men. The risk of hyperuricemia in young and middle-aged male decreased ( OR 0.83 and 0.84, respectively, P<0.01) for every 1-point increase in LSI. Exercise and body mass index were independently associated with hyperuricemia in the young male group ( OR 0.83 and 0.54, respectively, P<0.05). Exercise, body mass index, and alcohol drinking were independently associated with hyperuricemia in the middle-aged male group ( OR 0.85, 0.51 and 0.65, respectively, P<0.05). Conclusion:LSI is an independent factor associated with hyperuricemia in young and middle-aged men and a healthy lifestyle has a protective effect on serum uric acid levels in young and middle-aged men.

Research on merging methods and influencing factors of health state disutility values estimation ：taking diarrhea caused by antitumor drugs as an example / 中国药房

OBJECTIVE To explore the merging methods and influencing factors of health state disutility values estimation. METHODS Retrieved from 6 Chinese and English databases such as CNKI and PubMed ，the literatures about disutility values of diarrhea caused by antitumor drugs were collected from the inception to July 2021. After 2 researchers independently screened the literature，extracted the data ，assessed the quality ，the Meta-analysis and regression analysis were conducted using Stata 16.0 software. RESULTS Fifteen literatures were included. The results of Meta-analysis showed that diarrhea caused by antitumor drugs had a significant impact on health utility [ MD＝－0.26，95％CI（－0.30，－0.22），P＜0.05]. The results of subgroup analysis showed that the disutility values of the 3 types of negative value ，non-negative value changed into negative value ，and non-negative value combined with basic state changed into to negative value were MD ＝－0.14，95％CI（－0.19，－0.09）；MD＝－0.46，95％CI （－0.56，－0.36）；MD＝－0.12，95％CI（－0.20，－0.05），respectively. Meta regression results showed that the year of publication ， survey country/region ，severity of adverse events ，basic state settings ，utility estimation tools ，utility report types ，and utility statistical methods significantly affected the value of diarrhea disutility （P＜0.05）. CONCLUSIONS Disutility values for treatment-related symptoms or complications should be fully considered when inputting the parameters to the economic evaluation model. In the study or application of disutility values ，the types of utility reports should be distiguished ，and the core influencing factors such as the investigation country or region ，the severity of symptoms or complications ，and whether the basic state is set should be focus on.

Postoperative ileus after laparotomy for gastrointestinal cancer treated with electroacupuncture: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on postoperative ileus after laparotomy for gastrointestinal cancer.@*METHODS@#A total of 90 patients with postoperative ileus after laparotomy for gastrointestinal cancer were randomized into an EA group and a conventional treatment group, 45 cases in each one. In the conventional treatment group, the postoperative fast track surgical regimen was accepted. In the EA group, on the base of the treatment as the conventional treatment group, acupuncture was applied to Zusanli (ST 36), Shangjuxu (ST 37), Yinlingquan (SP 9) and Taichong (LR 3) and electric stimulation was attached on Zusanli (ST 36) and Yinlingquan (SP 9), with continuous wave, 2 Hz in frequency and 3-5 mA in intensity. Acupuncture was provided once daily till the onset of postoperative exhaust and defecation. The first postoperative exhaust time, the first postoperative defecation time, the postoperative hospital stay and the wound pain under standing on the next morning after entering group were compared in the patients between the two groups. The impact of the EA expectation was analyzed on the first postoperative exhaust time, the first postoperative defecation time and the postoperative hospital stay separately.@*RESULTS@#The first postoperative exhaust time and the first postoperative defecation time in the EA group were earlier than the conventional treatment group (P<0.05), the postoperative hospital stay was shorter than the conventional treatment group (P<0.05), and the rate of wound pain in the postoperative standing was lower than the conventional treatment group (P<0.05). EA expectation had no obvious correlation with the clinical therapeutic effect (P>0.05).@*CONCLUSION@#EA can relieve postoperative ileus symptoms, alleviate pain and shorten hospital stay in the patients after laparotomy for gastrointestinal cancer.

Study of health state disutility value estimation of malignant tumor drugs-related adverse events ：a systematic review / 中国药房

OBJECTIVE To provide methodology re ference for conducting health state disutility estimation and calculating health output in pharmacoeconomic evaluation. METHODS Literatures about health state disutility estimation of malignant tumor drugs-related adverse events were retrieved from 3 Chinese databases such as CNKI ，Wanfang database and VIP and 3 English database such as PubMed ，Web of Science and the Cochrane Library from inception to July 2021. After 2 researchers independently screened the literature and extracted the data ，qualitative analysis was conducted. The modified decision-making technical support documents of the National Institute for Health and Care Excellence were used for quality evaluation. The practice and existing problems of health state disutility measurement were summarized to put forward some suggestions. RESULTS A total of 77 literatures were included. The first literature was published in 1991，and the number of publications increased in a fluctuating manner. 77 literatures involved 120 kinds of adverse events ，mainly utility studies （49，63.64％），only 3 （3.90％） were investigated in China. A total of 35 literatures（45.45％）had no statement of study design type ，48（62.34％）had no statement of health status development method ，52（67.53％）had no statement of health status verification method ，46（59.74％）set and explained the basic health status ，and 20（25.97％）were ranked for the health status . The utility measurement tools used were mainly the standard game method and the European five-dimensional health scale （23 literatures each ，accounting for 29.87％）. The research objects of 45 literatures（58.44％）were patients ，and 63（81.82％）did not specify the representative test of the population. Utility report types included negative value ，non-negative value and non-negative value of consolidated basic status. A total of 45 literatures（58.44％）had no statement of statistical method of utility. Overall quality score of included studies was 0.683. CONCLUSIONS The current disutility estimation include 4 key links of basic study design ， health status confirmation， utility estimation survey and survey data E-mail：luyuqiong96@foxmail.com statistics. The deficiencies of related studies are the lack of data based on the Chinese population ，the inconsistent type ofresult reporting ，and the incomplete report of measurement- related critical items. It is recommended to standardize the basic implementation path of disutility estimation ，formulate guidelines for health status utility value estimation ，and strengthen multidisciplinary cooperation so as to improve the quality of health status utility value estimation .

Effects of regular aerobic exercise on brachial ankle pulse wave velocity in middle-aged and elderly people / 中华老年医学杂志

Objective:To investigate the effects of regular aerobic exercise on brachial ankle pulse wave velocity(baPWV)in middle-aged and elderly people.Methods:This was a cross-sectional study.A total of 7993 subjects receiving health examination at the Taihu Sanatorium of Jiangsu Province were enrolled, including 4 371 males and 3 622 females, with an average age of 55.8 years(±7.9).Information on exercise, alcohol consumption, smoking, body mass index, baPWV, blood pressure, resting heart rate, fasting blood glucose, total cholesterol(TC), triglycerides(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C)and uric acid in all subjects were collected and recorded.Based on exercise habits, subjects were divided into the no exercise group(n=489), the occasional exercise group(n=3 222, exercise<3 times or<90 min per week)and regular exercise group(n=4 282, exercise 3-5 times or >90 min per week).Results:For male subjects, differences in baPWV between the no exercise group(1 747.37±346.07 cm/s), the occasional exercise group(1 486.77±195.15 cm/s)and the regular exercise group(1 449.77±219.50 cm/s)were statistically significant( P<0.05).For female subjects, difference in baPWV between the no exercise group(1865.05±120.19)cm/s, the occasional exercise group(1 593.18±332.51)cm/s and the regular exercise group(1 227.81±150.89)cm/s were also statistically significant( P<0.05).With increased time of exercise per week, the levels of systolic blood pressure, diastolic blood pressure, resting heart rate, fasting blood glucose, TG and uric acid in different exercise groups decreased gradually for both men and women.Multivariate linear regression analysis showed that exercise, alcohol consumption, systolic blood pressure, diastolic blood pressure and fasting blood glucose were independent risk factors for baPWV in men(all P<0.05)and that exercise, systolic blood pressure, diastolic blood pressure, resting heart rate and fasting blood glucose were the independent risk factors for baPWV in women(all P<0.05).Trend analysis showed that with increased time of exercise per week, the rate of abnormal baPWV decreased gradually in both men and women( χ2 values were 74.67 and 1545.54, respectively, P<0.01). Conclusions:Regular aerobic exercise can improve baPWV, systolic blood pressure, diastolic blood pressure, resting heart rate, fasting blood glucose, TG and uric acid in middle-aged and elderly people.Exercise is an independent influencing factor for baPWV in middle-aged and elderly people and exercise 3-5 times or more than 90 min per week is beneficial to cardiovascular health in middle-aged and elderly people.

Research progress in role and mechanism of neutrophils in tissue repair / 中华创伤杂志

Damage to skin, muscle, bone and nerve tissues can result in various degrees of damage to the body, leading to organ dysfunction even life-threatening. To restore the structure and function of the damaged tissues, various immune cells and histocytes have successively participated in the tissue repair process. As the terminally differentiated white blood cells, neutrophils can remove necrotic tissue, debris and pathogens via phagocytosis and release of antimicrobial peptides after tissue injury to provide conditions for subsequent tissue repair process. However, enhanced neutrophils recruitment as well as excessive inflammatory response may also aggravate tissue damage. In recent years, more and more evidences indicate that neutrophils display plasticity and heterogeneity and that play critical roles in the initiation of tissue repair, promotion of angiogenesis, regulation of cell proliferation and so on. Herein, the authors review the recruitment, phenotype and function, role and outcome of neutrophils during tissue repair so as to provide references for future studies.

Effect of Tanhuo Formula on the expression of Caspase-3, GFAP, and angiogenesis in rats with cerebral ischemia / 国际中医中药杂志

Objective:To study the effect of Tanhuo Formula (THW) on the expression of Glial Fibrillary Acidic Protein (GFAP), Caspase-3 and angiogenesis.Methods:Rats were divided into sham group, model group, low-dose THW group, medium-dose THW group, high-dose THW group and Ginaton group according to random number table method. Except the sham group, rats in other groups were subjected to the middle cerebral artery occlusion via a suture method. After 2 hours,rats in the low, medium and high dose of THW groups were gavaged with 0.92, 1.84 and 3.68 g/kg of THW dry extract powder solution respectively, and the Ginaton group were gavaged with 60 mg/kg of Ginaton, once every 24 hours for 3 days. Rats in sham operation group and model group were given equal volume of normal saline by gavage. The limb symmetry score was used to evaluate limb dysfunctions. The immunofluorescence staining of GFAP and Caspase-3 were applied to assess astrocyte activation and neuronal apoptosis, respectively. The double-labeled immunofluorescence staining of platelet-endothelial cell adhesion molecule (CD31) and chondroitinsulphate peoteoglycan (NG2) were performed to detect angiogenesis.Results:Compared with the model group, rats in the high-dose of THW group showed increased limb symmetry score ( P<0.01 or P<0.05), increased number of Caspase-3 (cortex: 765.0±122.4 vs. 1 131.0±392.9; striatum: 895.9±389.8 vs. 1 401.9±453.1) ( P<0.01 or P<0.05) and CD31 +/NG2 + (cortex: 1 355.0±257.9 vs. 825.4±308.1; striatum: 1 290.9±400.9 vs. 675.2±259.7) ( P<0.01) positive cells in the periinfarct cortex and striatum, and attenuated the integrated optical density of GFAP in the perilesional cortex (4 210.00±1 226.38 vs. 7 935.78±2 001.98) ( P<0.01). Conclusions:THW could ameliorate the limb functional disorders, inhibit astroglia activation, down-regulate the expression of Caspase-3, and enhanced angiogenesis in MCAO rats.