Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Outbreaks of hand-foot-mouth disease (HFMD) have occurred many times and caused serious health burden in China since 2008.Application of modem information technology to prediction and early response can be helpful for efficient HFMD prevention and control.A seasonal auto-regressive integrated moving average (ARIMA) model for time series analysis was designed in this study.Eighty-four-month (from January 2009 to December 2015) retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling.The coefficient of determination (R2),normalized Bayesian Information Criterion (BIC) and Q-test P value were used to evaluate the goodness-of-fit of constructed models.Subsequently,the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016.The best-fitted seasonal ARIMA model was identified as (1,0,1)(0,1,1)12,with the largest coefficient of determination (R2=0.743) and lowest normalized BIC (BIC=3.645) value.The residuals of the model also showed non-significant autocorrelations (PBox-Ljung (Q)=0.299).The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval,including a major peak during April to June,and again a light peak for September to November.The ARIMA model proposed in this study can forecast HFMD incidence trend effectively,which could provide useful support for future HFMD prevention and control in the study area.Besides,further observations should be added continually into the modeling data set,and parameters of the models should be adjusted accordingly.

Abstract: Objective　To investigate the drug demand and related influencing factors of AIDS non-occupational post-exposure prophylaxis (nPEP) among men who have sex with men (MSM) in Wuhan, and to provide a scientific basis for the development of subsequent intervention policies for MSM. Methods　With the assistance of social organizations in Wuhan, MSM was recruited by the snowball method to carry out an online questionnaire survey to collect information on demographics, AIDS-related knowledge, high-risk behaviors, and the need for nPEP medication. The χ2 test and unconditional Logistic regression were used to analyze the related factors of the demand for nPEP medication. Results　A total of 308 valid subjects were included in this study, with predominantly 18-29 years old (78.57%, 242/308). The self-reported sexual orientation was mainly homosexuality (82.47%, 254/308), and the awareness rate of AIDS knowledge was high (89.29%, 275/308). Among the survey respondents, 35.06% (108/308) did not know the situation of HIV infection among MSM population in Wuhan; 55.19% (170/308) had two or more same-sex sexual partners in the last six months; 90.91% (280/308) had heard of nPEP before participating in this survey. After passing nPEP and informing the protective effect of nPEP, 59.42% (183/308) of them needed nPEP. After HIV exposure, 73.38% (226/308) were willing to spend money to buy nPEP drugs, and 88.64% (273/308) were willing to take nPEP drugs because of the known side effects. Logistic regression analysis showed that in the last six months, the needs for taking nPEP medication in those who had 2 or more same-sex sexual partners (OR=2.121, 95%CI: 1.329-3.386) and who had received peer education (OR=1.740, 95%CI: 1.088-2.781) were higher than those of those who had a same-sex sexual partner in the last six months and who had not received peer education. Conclusions　The MSM population in Wuhan has a great demand for nPEP drugs, and peer education is an important way to carry out nPEP publicity and promotion. At the same time, we should continue to strengthen warning publicity and education and behavioral intervention to reduce MSM risky sexual behaviors and reduce new HIV infections.

OBJECTIVEThis study aimed to explore the scene-trait coping style of military rescuers in Wenchuan earthquake in an effort to provide scientific evidences for mental intervention program for Chinese military personnel.

METHODSBy cluster sampling, a total of 151 military rescuers and 331 control servicemen were administered the military personnel scene-trait coping style scale (MPSTCSS).

RESULTSAll active coping factor scores, and passive coping factor scores of affection, health and economy in the rescuer group were significantly higher than those in control group (P < 0.05). The 21-above age subgroup, the 3-year plus service subgroup, and the officer subgroup had significantly higher active coping factor scores on military tasks, military experience and personal development than those of the 21-below age subgroup, 3-year minus service subgroup and the soldier subgroup, respectively (P < 0.05 or P < 0.01).

CONCLUSIONThe earthquake relief servicemen can cope with stressful situations better than control group by taking active coping style. The officers, servicemen older than 21 years, and servicemen with more service duration than 3 years could usually take active coping style.

Adaptation, Psychological ; Disasters ; Earthquakes ; Humans ; Military Personnel ; psychology ; Stress, Psychological

OBJECTIVETo retrospectively analysis the treatment characteristics of the systemic situation in patients with crush syndrome after Wenchuan earthquake happened in May 12th, 2008.

METHODSForty-nine patients with crush syndrome and subsequent acute renal failure (ARF) due to the earthquake were treated in West China Hospital. All of patients had been rescued from buildings that collapsed in Wenchuan earthquake. The major associated injuries were in the low extremities and upper extremities. 49 patients developed ARF with increased concentrations of serum creatinine (mean 64 022 U/L) had underwent haemodialysis. Hyperkalaemia was seen in 9 patients and four of them underwent haemodialysis. 49 patients were administered hemodialysis.

RESULTSNo patient died. All patients who suffered from the ARF were weaned from hemodialysis after admitted 7 to 35 days. Forty-five extremities underwent amputations and 52 extremities had fasciotomy.

CONCLUSIONSCrush syndrome requires urgent recognition and prompt surgical treatment with simultaneous measures to control hyperkalemia and ARF. The authors believe that immediate intensive care therapy and multi-subjective coordination would have improved the survival rate.

Acute Kidney Injury ; etiology ; surgery ; therapy ; Adolescent ; Adult ; Aged ; Amputation ; Child ; Crush Syndrome ; etiology ; surgery ; therapy ; Decompression, Surgical ; Earthquakes ; Female ; Humans ; Male ; Middle Aged ; Renal Replacement Therapy ; Retrospective Studies ; Treatment Outcome ; Wounds and Injuries ; complications

Objective: To investigate the effect of Rhei Radix et Rhizoma on gastrointestinal function of normal rats and explore its therapeutic mechanism,and compare the difference of this herb before and after simmering. Method: Healthy SD rats were randomly divided into 7 groups,including the blank group,the high,medium and low dose groups of raw Rhei Radix et Rhizoma(1.5,3.0,6.0 g·kg^-1·d^-1) and the high,medium and low dose groups of simmered Rhei Radix et Rhizoma(1.5,3.0,6.0 g·kg^-1·d^-1),eight rats in each group were continuous intragastric administration for 10 days,the effect of Rhei Radix et Rhizoma on gastrointestinal function of rats were evaluated by body weight,food intake,gastric remnant rate,small intestine propelling rate,stomach weight coefficient and gastrointestinal tissue morphology;enzyme-linked immunosorbent assay(ELISA) was used to detect contents of motilin(MTL) in rat plasma and gastrin(GAS),tumor necrosis factor-α(TNF-α),interleukin-10(IL-10) in rat serum,the mechanism of effect of Rhei Radix et Rhizoma on gastrointestinal function was explored and the effect of Rhei Radix et Rhizoma on gastrointestinal function of normal rats before and after simmering was compared. Result: In each administration group,weight growth of rats was slowed down,gastric emptying and intestinal propulsion were inhibited,inflammatory reaction was triggered,and gastric mucosal injury was increased.Compared with the blank group, except for the low-dose and medium-dose groups of simmered Rhei Radix et Rhizoma,stomach weight coefficient,gastric remnant rate and content of TNF-α of rats were significantly increased(P<0.05,P<0.01), and the content of IL-10 was significantly reduced, in addition to the low-dose group of simmered Rhei Radix et Rhizoma,the weight,small intestine propelling rate,contents of GAS and MTL of rats were significantly decreased(P<0.05,P<0.01).Compared with the isodose raw Rhei Radix et Rhizoma group,the weight,small intestine propelling rate,contents of GAS,IL-10 and MTL were all increased with different degrees, the gastric weight coefficient,gastric remnant rate and content of TNF-α of rats were all decreased to different degrees. Conclusion: Gastrointestinal dysfunction caused by Rhei Radix et Rhizoma is related to inhibiting the expression of gastrointestinal hormones and promoting the expression of inflammatory cytokines, in addition,the effect of "stomach injured by bitterness and cold property" of Rhei Radix et Rhizoma is weakened after simmering,which provides scientific basis for clinical rational use of Rhei Radix et Rhizoma.

OBJECTIVE: To evaluate the clinical efficacy of local infiltration anesthesia of ropivacaine combined with compound betamethasone for postoperative analgesia in patients with hallux valgus. METHODS: From September 2019 to December 2020, 48 patients with hallux valgus were treated surgically. According to different postoperative analgesia methods, the patients were divided into combined local infiltration group and intravenous analgesia pump group. There were 24 cases, in the combined local infiltration group including 2 males and 22 females;the age ranged from 21 to 78 years old, with an average of (58.3±7.7) years old;soft tissue release and chevron osteotomy were performed in 15 cases and metatarsophalangeal joint fusion in 9 cases;immediately after operation, 20 ml of ropivacaine combined with compound betamethasone mixed diluent was used for local infiltration anesthesia once. There were 24 patients in intravenous analgesia pump group, including 3 males and 21 females;the age ranged from 23 to 81 years old, with an average of(56.8±8.3) years old;soft tissue release and Chevron osteotomy were performed in 17 cases and metatarsophalangeal joint fusion in 7 cases;immediately after operation, intravenous analgesia pump was used for analgesia. The basic flow was 2 ml / h;the self control dose was 0.5 ml;and the locking time was 15 min. Visual analogue scale (VAS) was recorded at 12, 24, 48 and 72 hours after operation;and the VAS was recorded at 24 hours after operation. The occurrence of adverse drug reactions at 0 to 12 hours, 12 to 24 hours and 24 to 48 hours after operation were recorded;and the healing of incision was recorded. RESULTS: All patients were followed up, and the duration ranged from 14 to 17 days, with a mean of (14.60±0.92) days. There was significantdifference in VAS at 12, 24 and 48 hours between the combined local infiltration group and the intravenous analgesia pump group( CONCLUSION Compared with intravenous analgesia pump group, ropivacaine combined with compound betamethasone can significantly reduce postoperative wound pain without increasing adverse drug reactions, and does not increase wound infection.
Adult ; Aged ; Aged, 80 and over ; Analgesia ; Anesthesia, Local ; Bunion ; Feasibility Studies ; Female ; Hallux Valgus/surgery* ; Humans ; Male ; Middle Aged ; Pain, Postoperative/drug therapy* ; Young Adult

Air Pollution ; China ; Humans ; Meteorological Concepts ; Outpatients ; Particulate Matter/analysis* ; Skin Diseases/epidemiology*

Parkinson's disease (PD) is a progressive neurodegenerative disease with a high clinical heterogeneity. According to its motor symptoms, PD patients are divided into predominant tremor-dominant, postural instability and gait difficulty-dominant/akinetic-rigid and mixed subtypes. Different subtypes show different prognostic characteristics and different sensitivities to drugs. Therefore, the early classification of PD is of great significance for the treatment and prognosis of the disease. This paper reviews the clinical classification methods of different subtypes of PD, summarizes the latest biochemical markers and imaging features, and analyzed the differences in incidence, prognosis and pathological mechanism. The current clinical treatment drugs and methods have been preliminarily targeted for treatment based on PD classification, and there are many animal models of PD subtypes have been studied, providing new methods and strategies for mechanism research and preclinical pharmacodynamics evaluation of PD subtypes.

Fusion between the transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog (TMPRSS2-ERG fusion) is a common genetic alteration in prostate cancer among Western populations and has been suggested as playing a role in tumorigenesis and progression of prostate cancer. However, the prevalence of TMPRSS2-ERG fusion differs among different ethnic groups, and contradictory results have been reported in Asian patients. We aim to evaluate the prevalence and significance of TMPRSS2-ERG fusion as a molecular subtyping and prognosis indicator of prostate cancer in Asians. We identified the fusion status in 669 samples from prostate biopsy and radical prostatectomy by fluorescence in situ hybridization and/or immunohistochemistry in China. We examined the association of TMPRSS2-ERG fusion with clinicopathological characteristics and biochemical recurrence by Chi-square test and Kaplan-Meier analysis. Finally, a systematic review was performed to investigate the positive rate of the fusion in Asian prostate cancer patients. McNemar's test was employed to compare the positive rates of TMPRSS2-ERG fusion detected using different methods. The positive rates of TMPRSS2-ERG fusion were 16% in our samples and 27% in Asian patients. In our samples, 9.4% and 19.3% of cases were recognized as fusion positive by fluorescence in situ hybridization and immunohistochemistry, respectively. No significant association between the fusion and clinical parameters was observed. TMPRSS2-ERG fusion is not a frequent genomic alteration among Asian prostate cancer patients and has limited significance in clinical practices in China. Besides ethnic difference, detection methods potentially influence the results showing a positive rate of TMPRSS2-ERG fusion.
Aged ; China ; Humans ; Male ; Middle Aged ; Oncogene Fusion/genetics* ; Oncogene Proteins, Fusion/genetics* ; Prostatic Neoplasms/genetics* ; Serine Endopeptidases/genetics* ; Transcriptional Regulator ERG/genetics*