ObjectiveTo comprehensively assess the clinical value of Duliang soft capsules in the treatment of migraine with wind-cold blood stasis syndrome， and to provide guidance for national medical decision-making， clinical drug promotion， and pharmaceutical services. MethodThe evaluation of Duliang soft capsules' clinical value was conducted in accordance with the Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs （Trial Version， 2021） using a combination of qualitative and quantitative methods. Utilizing the CSC v2.0 software， this study conducted a comprehensive clinical evaluation of Duliang soft capsules across the "6+1" dimensions， including safety pre- and post-market launch， effectiveness in treating migraine， economy （cost-effectiveness）， and innovation， suitability， accessibility， and traditional Chinese medicine （TCM） characteristics in both its technology and clinical applications. ResultSafety： Duliang soft capsules were found to have good safety based on evidence from known adverse reactions （spontaneous reporting system （SRS） data， literature data， etc.）， pre-marketing toxicological research， and post-marketing drug monitoring. Effectiveness： A meta-analysis indicated that the combination of Duliang soft capsules and western medicine was more effective than Western medicine alone in the treatment of migraine. The product's effectiveness was rated as "Best" based on the quality and value of the evidence. Economy： Duliang soft capsules are moderately priced and categorized as a Type B medical insurance product. Economic research indicated that the combination of Western medicine and Duliang soft capsules was more cost-effective than Western medicine alone. The product's economy was rated as "Better". Innovation： Duliang soft capsules， with Angelicae Dahuricae Radix and Chuanxiong Rhizoma as the main components， hold one invention patent and have been awarded the China Patent Excellence Award. The pharmaceutical company has introduced innovative extraction （CO₂ supercritical extraction technology） and formulation （soft capsule） processes. The product's innovation was rated as "Better". Suitability： A questionnaire survey on Duliang soft capsules showed that it was well-suited for both patients and healthcare professionals. The product received a comprehensive assessment of suitability through the "Evaluation of Chinese Patent Medicine Information Services". The product's suitability was rated as "Best". Accessibility： Duliang soft capsules are moderately priced， making them accessible and affordable. The product's accessibility was rated as "Good" based on evidence from these three aspects. TCM characteristics： The formulation of Duliang soft capsules can be traced back to WANG Qiu's Selected Formulas from the Praiseworthy Studio （Shi Zhai Bai Yi Xuan Fang） from the Song Dynasty， and it was documented in ZHANG Jiebin's The Complete Works of Zhang Jing-yue （Jing Yue Quan Shu） as "Duliangwan". The product has been extensively studied with over 2000 clinical cases since its market launch， and its TCM characteristics were rated as outstanding with sufficient evidence. ConclusionThe comprehensive clinical value evaluation of Duliang soft capsules demonstrated its high effectiveness， suitability， and accessibility， and outstanding TCM characteristics. The product's safety， economy， and innovation received good ratings. In summary， Duliang soft capsules exhibited significant clinical value and outstanding TCM characteristics， the evidence was sufficient， and the result was confirmed， providing crucial references for clinical decision-making and pharmaceutical management.

Nitroxide radicals are a kind of stable organic free radicals.Due to the presence of N-O·and unpaired electrons in its structure,it has many characteristics,and thus can be used as a spin marker to explore the mechanism of biological reactions;with its magnetic properties,it can be used for the development of multifunctional magnetic molecular materials and used as a polymerization inhibitor and catalyst in organic reactions.More importantly,it has a variety of biological activities such as anti-oxidation and anti-tumor,and so has attracted much attention in the research and development of new drugs.For example,the spin labeling of nitroxide radicals on anticancer drug podophyllotoxin can enhance the efficacy and reduce the toxicity,and can be easily to be absorbed by the body,thus obtaining a new anti-cancer drug 4-[4″-(2″,2″,6″,6″-tetramethyl-1″-piperidinyloxy nitroxide radical)amino]-4′-demethyl epipodophyllotoxin(GP-7).It is an effective way to seek new drugs by introducing pharmacophore to modify nitroxide radicals or it can be spin-labeled on active natural products to obtain new compounds with high efficiency and low toxicity.The research progress of derivatives and its biological activitives of nitroxide radicals are summarized,aiming to provide theoretical basis for the developing and utilizing of nitroxide radicals and searching for new drugs.

Objective To investigate the relationships between the expression levels of tumor necrosis factor receptor associated factor 4 (TRAF4) and ribosomal S6 protein kinase 4 (RSK4) protein in gastric cancer tissues and the recurrence after laparoscopic radical gastrectomy. Methods In total, 176 patients were divided into the recurrence and non-recurrence group, and the expression levels of TRAF4 and RSK4 protein in cancer and adjacent tissues and in gastric cancer tissues in the recurrence and non-recurrence group were compared. The influencing factor of recurrence and the efficacy of TRAF4 and RSK4 protein expression in predicting recurrence were analyzed. Results The positive expression rate of TRAF4 protein in gastric cancer tissues was higher than that in adjacent tissues (P < 0.05) and that in the recurrence group was higher than that in the non-recurrence group (P < 0.05). The positive expression rate of RSK4 protein in gastric cancer tissues was lower than that in adjacent tissues (P < 0.05) and that in the recurrence group was lower than that in non-recurrence group (P < 0.05). The largest tumor diameter 5 cm, poor differentiation, TNM Ⅲ stage, depth of invasion T3-T4, lymph node metastasis, absence of adjuvant chemotherapy after operation, positive expression of TRAF4 and RSK4 protein, and regular diet w influenced the post-operative recurrence (all P < 0.05). The accuracy of TRAF4 and RSK4 protein in gastric cancer tissues in combined predicting the recurrence was 83.52%. Conclusion The expression of TRAF4 protein is high, and the RSK4 protein is low in gastric cancer tissue, which are related to recurrence.

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

Objective:To investigate the neural mechanism of long-term exposure to high altitudes environment on the processing stage of perceptual closure.Methods:A cross-sectional study was conducted. Thirty college students who first entered the plateau area (at an altitude of 3 658 m) and had lived in high-altitude areas for two years were selected as high altitude group (HA group), and 29 college students matched in age, gender and education level who had never been to the plateau area were selected as sea level group (SL group). The differences of basic physiological parameters were compared between the two groups.The face pairwise comparison paradigm was applied in the subjects of the two groups and the differences between the two groups were compared by event-related potentials (ERPs) technology. SPSS 22.0 software was used for statistical analysis, and the mean ± standard deviation was used for statistical description. Independent sample t test was used for comparison of physiological data between the two groups, and repeated measurement variance analysis was used for ERP data. Results:The physiological results revealed that the HA group had a higher pulse rate((86.71±10.82)/min, (75.97±11.28)/min ; t=-3.19, P=0.002) and diastolic blood pressure than the SL group ((75.93±9.19)mmHg, ( 68.59±11.42) mmHg ; t=-3.20, P=0.002). The oxygen saturation level was significantly lower than that of SL group ((90.77±2.25)%, (98.31±1.56) %) ; t=14.00, P<0.001). In the face pairwise comparison paradigm test, the main effect of P1 latency of ERP was significant.Compared with SL group, HA group showed significantly shortened latency of P1 ((105.10±15.59) ms, (128.35±14.40)ms, P<0.001). The main effect of group of N170 amplitude was significant, HA group was larger than that of SL group((-7.57±3.83) μV, ( -5.11±3.26) μV, P=0.005). The interaction effect between group and hemisphere of NCL amplitude was significant ( F(1, 57)=9.72, P=0.003). Simple effect test showed that the amplitude on the right hemisphere of SL group was significantly larger than that on the left hemisphere((0.46±1.31) μV), (1.16±1.33) μV ). The latency of P1 was significantly correlated with heart rate( r=-0.46, P<0.01), oxygen saturation level( r=0.64, P<0.01) and diastolic blood pressure( r=-0.26, P=0.049). Conclusion:After long-term exposure to high altitude, the neural response related to early visual perception is faster. More psychological resources are recruited during the face structural encoding stage. Contra-lateral compensating effect appeares in the stage of perceptual closure.

Objective:To investigate the current status of work-related musculoskeletal disorders (WMSDs) in automobile assembly workers, as well as the distribution of WMSDs at multiple sites and related influencing factors.Methods:From March to July 2019, cluster sampling was performed to select 663 male automobile assembly workers as respondents, and the musculoskeletal injury questionnaire was used to investigate their general status and working condition. A multinomial logistic regression analysis was used to analyze the influencing factors for WMSDs at multiple sites.Results:The detection rate of WMSDs within the past 7 days was 37.9% (251/663) among the automobile assembly workers, and the detection rate of WMSDs within the past 1 year was 51.9% (344/663) . Of all workers, 13.6% (90/663) had WMSDs involving only 1 site, while 38.3% (254/663) had WMSDs involving 2 or more sites. The multinomial logistic regression analysis showed that frequent turns during work was a risk factor for WMSDs involving 1-3, 4-6, and 7-9 sites (odds ratio [ OR]=1.65, 2.47, and 3.65, respectively) . Repeated action of lower extremities and ankles was a risk factor for WMSDs involving 4-6 and 7-9 sites ( OR=2.15 and 2.98, respectively) . Working in an uncomfortable position was a risk factor for WMSDs involving 1-3, 4-6, and 7-9 sites ( OR=1.95, 2.67, and 3.04, respectively) . Prolonged standing during work was a risk factor for WMSDs involving 1-3 and 4-6 sites ( OR= 1.87 and 1.79, respectively) . Working overtime was a risk factor for WMSDs involving 7-9 sites ( OR=5.48) . Adequate time for rest was a protective factor against WMSDs involving 1-3 and 4-6 sites ( OR=0.50 and 0.31, respectively) . Conclusion:There is a high detection rate of WMSDs in automobile assembly workers, and WMSDs at multiple sites are more common than WMSDs at a single site. Poor position and organizational management factors are risk factors for occupational WMSDs at multiple sites.

Objective:To investigate the current status of work-related musculoskeletal disorders (WMSDs) in automobile assembly workers, as well as the distribution of WMSDs at multiple sites and related influencing factors.Methods:From March to July 2019, cluster sampling was performed to select 663 male automobile assembly workers as respondents, and the musculoskeletal injury questionnaire was used to investigate their general status and working condition. A multinomial logistic regression analysis was used to analyze the influencing factors for WMSDs at multiple sites.Results:The detection rate of WMSDs within the past 7 days was 37.9% (251/663) among the automobile assembly workers, and the detection rate of WMSDs within the past 1 year was 51.9% (344/663) . Of all workers, 13.6% (90/663) had WMSDs involving only 1 site, while 38.3% (254/663) had WMSDs involving 2 or more sites. The multinomial logistic regression analysis showed that frequent turns during work was a risk factor for WMSDs involving 1-3, 4-6, and 7-9 sites (odds ratio [ OR]=1.65, 2.47, and 3.65, respectively) . Repeated action of lower extremities and ankles was a risk factor for WMSDs involving 4-6 and 7-9 sites ( OR=2.15 and 2.98, respectively) . Working in an uncomfortable position was a risk factor for WMSDs involving 1-3, 4-6, and 7-9 sites ( OR=1.95, 2.67, and 3.04, respectively) . Prolonged standing during work was a risk factor for WMSDs involving 1-3 and 4-6 sites ( OR= 1.87 and 1.79, respectively) . Working overtime was a risk factor for WMSDs involving 7-9 sites ( OR=5.48) . Adequate time for rest was a protective factor against WMSDs involving 1-3 and 4-6 sites ( OR=0.50 and 0.31, respectively) . Conclusion:There is a high detection rate of WMSDs in automobile assembly workers, and WMSDs at multiple sites are more common than WMSDs at a single site. Poor position and organizational management factors are risk factors for occupational WMSDs at multiple sites.

Objective To investigate the correlation value between the impression depth of umbilical cord around neck and the blood flow indexes of middle cerebral artery (MCA) and umbilical artery (UA) in fetus.Methods Totally 139 late pregnancy fetuses of umbilical cord around neck and 28 normal fetuses were enrolled in the study.The systolic maximum velocity/diastolic minimum velocity (S/D),resistence index (RI),pulsatility index (PI) of MCA and UA in fetuses were measured by Doppler ultrasound,and the correlation of the pressure trace depth with MCA and UA blood flow parameters were analyzed.Results The pressure trace depth of umbilical cord around neck and the S/D,RI,PI of MCA were positively correlated (one round of umbilical cord around neck,r=0.32,0.32,0.35,two or more rounds of umbilical cord around neck,r=0.71,0.69,0.53,all P＜0.05).The pressure trace depth of umbilical cord around neck and the S/D,RI,PI of UA had no correlation.Compared with normal fetuses,the parameters of UA had no significant differences in fetuses with umbilical cord around neck (all P＞0.05).The S/D,RI,PI of MCA in fetuses with pressure trace depth ≥0.80 cm and fetuses with two or more rounds of umbilical cord around neck were higher than those of normal fetuses (all P＜0.05).Fetuses with two or more rounds of umbilical cord around neck had obviously increased cesarean rate compared with normal fetuses.Compared with normal fetuses,the fetuses with pressure trace depth ≥0.80 cm had increased abnormal fetal heart rate,prolonged labor time during the second stage (all P＜0.05).Conclusion In late pregnancy fetuses with umbilical cord around neck,the blood flow parameters of MCA are more sensitive than those of UA.The pressure trace depth ≥ 0.80 cm may lead to intrauterine fetal anoxia.

Objective To explore the clinical effects of oxygen-driven atomized inhalation of recombinant human inter-feron-α2a injection in the treatment of infantile capillary bronchitis. Methods 240 infant patients with capillary bron-chitis were assigned to a control group and a treatment group according to their disease conditions, with 120 patients in each group. The control group received regular treatment(oxygen uptake, atomized inhalation of pulmicort respulas+nebulized terbutaline sulphate solution used for anti-inflammation and antiasthma, aspiration of sputum, antibiotics giv-en to infants suspected to be complicated with bacterial infection, intravenous drip of methylprednisolone given to in-fants with severe symptoms, etc.); The treatment group further received oxygen-driven atomized inhalation of 600,000 international units of recombinant human interferon-α2a injection, once a day for 5 days. Clinical effects and main ob-servational indices between the two groups were compared. Results Total effective rate was 95.0% in the treatment group and 78.3%in the control group, and the differences between the two groups were statistically significantly(P<0.05). Alleviating time of asthma, disappearing time of lung rale, time of persistent cough and hospitalization time in the treatment group were all lower than those in the control group, and the differences between the two groups were statisti cally significant (P<0.05). Significant adverse events were not detected during the treatment period of oxygen-driven atomized inhalation of recombinant human interferon-α2a injection applied by the infant patients. Conclusion Oxygen-driven atomized inhalation of recombinant human interferon-α 2a injection in the treatment of infantile capillary bron-chitis has an exact curative effect, and it is safe, which is worthy of clinical pediatric promotion and application.

Objective To examine the anticancer effect of a novel histone deacetylase inhibitor (HDACi), JZ004, on colon cancer cells HCT-8 and HT-29, and to investigate the molecular mechanisms of proliferation inhibition and apoptosis induction of cancer cells treated by JZ 004.Methods Colon cancer cells were treated with a series of concentrations of JZ004 .MTT assay was used to detect the proliferation of cancer cells .The cell cycle distribution and apoptosis were deter-mined by flow cytometry .Rhodamine 123 and DCFH-DA were applied to detect the mitochondrial membrane potential (ΔΨm) and reactive oxygen species ( ROS) production.The protein expressions of acetyl-histone H3, p21, cyclin-dependent kinase(CDK)4, Bcl-2, Mcl-1 and Bax were assayed by Western blotting .Results JZ004 was found to inhibit proliferation and induce apoptosis of colon cancer cells in a time-and dose-dependent manner , accompanied by a dose-dependent hyperacetylation of histone H3.JZ004 induced the cancer cell arrest in G 0/G1 phase by increasing the expres-sion level of p21 while CDK4 was downregulated .JZ004 also increased cellular ROS production and reduced ΔΨm by regu-lating the expressions of Bcl-2 family proteins .Conclusion As a novel HDACi , JZ004 effectively inhibits proliferation and increases ROS production to induce apoptosis of colon cancer cells .The results indicate that JZ004 is a potential compound to be developed as an anti-colon cancer agent for clinic application .