OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.

Objective To explore the dynamic changes and mechanisms of neurological and cognitive functions in mice with traumatic brain injury (TBI). Methods Totally 60 12⁃month⁃old Balb/ c mice were divided into control group (10 in group) and TBI group (50 in group). TBT model mice were divided into 5 subgroups according to the time of model construction, including model 1 day, model 1 day, model 3 day, model 7 day, model 14 days and model 28 days group with 10 in each group. At the 29th day of the experiment, neurological scores and step down tests were carried out. After the test, the mice were sacrificed for brains which were detected by immunohistochemistry staining, inflammatory cytokine tests and Western blotting. Results Compared with the control group, the neurological scores of mice in TBI group increased, and then decreased after the 7th day when the scores reached the peak. However, the latency of step down errors was lower than control group, and the number of step down errors was higher than control group which had no changes. Compared with the control group, the expression of lonized calcium⁃binding adapter molecule 1(IBA1), chemokine C⁃X3⁃C⁃motif ligand1 (CX3CL1), C⁃X3⁃C chemokine receptor 1(CX3CR1), NOD⁃like receptor thermal protein domain associated protein 3 (NLRP3), and phosphorylation nuclear factor(p⁃NF)⁃κB in TBI group increased and reached to the peak at the 7th day, and then started to decrease. At the same time, the levels of inflammatory cytokines interleukin⁃6(IL⁃6) and tumor necrosis factor⁃α(TNF⁃α) first increased to the peak, and then began to decrease. However, compared with the control group, the expression of amyloid β(Aβ) protein and p⁃Tau protein in the model group continued to increase at all time. Conclusion The TBI model caused continuous activation of microglia along with inflammatory response, which first increased and then decreased, resultsing in neurological scores changes. In addition, the inflammatory response may act as a promoter of Aβ protein deposition and Tau protein phosphorylation, leading to cognitive impairment in mice.

Objective To observe the influence of nintedanib ethanesulfonate soft capsules combined with tetrandrine tablets on pulmonary function and dyspnea symptoms in patients with connective tissue disease-related pulmonary interstitial fibrosis.Methods Patients with connective tissue disease-related pulmonary interstitial fibrosis were divided into treatment group and control group by cohort method.The control group was given basic treatment such as glucocorticoids and immunosuppressants according to the patient's condition;the treatment group was given ethanesulfonate nintedanib soft capsules(100 mg,bid)and tetrandrine tablets(40 mg,tid)on the basis of the control group,and the treatment course was 3 months.The clinical efficacy,severity of dyspnea[modified British Medical Research Council Dyspnea Scale(mMRC)and St.George's Respiratory Questionnaire(SGRQ)],pulmonary function indicators,pulmonary fibrosis score,and blood gas analysis indicators were compared between the two groups,and the safety was assessed.Results A total of 42 cases were included in the treatment group and the control group,respectively.The total effective rates of the treatment group and the control group were 92.86％(39 cases/42 cases)and 76.19％(32 cases/42 cases)respectively(P＜0.05).After treatment,the mMRC scores of the treatment group and the control group were(1.43±0.27)and(1.69±0.31)points;the SGRQ scores were(46.51±4.39)and(51.08±4.76)points;the forced expiratory volume in one second(FEV1)values were(64.96±6.55)％and(58.67±5.01)％;the fibrosis scores were(1.12±0.14)and(1.26±0.18)points;the partial pressure of arterial oxygen values were(80.31±7.03)and(75.02±6.94)mmHg.The above indexes of the treatment group were compared with those of the control group,and the differences were statistically significant(all P＜0.05).There were no adverse drug reactions in the treatment group,and the main adverse drug reactions in the control group were gastrointestinal discomfort.The total incidence rates of adverse drug reactions in the treatment group and the control group were 0 and 2.38％,respectively(P＞0.05).Conclusion Compared with basic treatment,nintedanib ethanesulfonate soft capsules combined with tetrandrine tablets can better improve the pulmonary fibrosis degree and dyspnea degree in patients with connective tissue disease-related pulmonary interstitial fibrosis,and delay the decline of pulmonary function of patients.

Objective:To explore the epidemiological characteristics and spatiotemporal clustering of foodborne infection of Vibrio ( V.) parahaemolyticus in Ningbo, Zhejiang Province, from 2014 to 2022, and provide reference and evidence for the prevention and control of related diseases. Methods:The incidence data on of foodborne infection of V. parahaemolyticus in Ningbo from 2014 to 2022 were collected from Ningbo Foodborne Disease Surveillance System, and the case counts and the positive rates in different districts (counties, cities) were calculated. Spatial autocorrelation analysis and spatiotemporal scanning analysis were conducted to analyze the spatiotemporal clustering of the diseases. Results:A total of 1 822 cases of foodborne infection of V. parahaemolyticus were reported in Ningbo from 2014 to 2022, with an overall positive rate of 3.78%. Spatial autocorrelation analysis showed that the positive rate of foodborne infection of V. parahaemolyticus in Ningbo was unevenly distributed from 2014 to 2022, Ninghai was a high-high clustering area, while Zhenhai was a high-low clustering area, and Jiangbei was a low-low clustering area. The annual incidence was high during July-September. Spatiotemporal scanning analysis found one class Ⅰ spatiotemporal clustering area and three class Ⅱ spatiotemporal clustering areas, with the class Ⅰ spatiotemporal clustering area being observed in Jiangbei and Zhenhai from 2019 to 2022. Conclusions:Spatiotemporal clustering of foodborne infection of V. parahaemolyticus existed in Ningbo from 2014 to 2022, with an annual high incidence period from July to September. The key areas for the prevention and control of foodborne infection of V. parahaemolyticus are coastal districts (counties, cities) in Ningbo.

ObjectiveTo evaluate the effectiveness and safety of Qiaoqi Formula （翘芪组方） for mild influenza. MethodsA randomized controlled study was designed， recruiting 74 patients with mild influenza， who were randomly divided into trial group and control group. The trial group took Qiaoqi Formula orally， 40ml each time， twice a day； the control group took Lianhua Qingwen Capsules （连花清瘟胶囊） orally， 1.4 g each time， three times a day. Both groups were treated for 3 consecutive days and follow-up for 4 consecutive days after treatment. The time for fever reduction including onset of fever reduction， complete fever reduction time， fever reduction rates at 24， 48 and 72 hours， improvement of influenza symptoms， total traditional Chinese medicine （TCM） symptom score， and safety indicators in two groups after treatment were recorded. ResultsSixty-five patients were ultimately included， including 36 in the trial group and 29 in the control group. Onset time of fever reduction in the trial group was （15.49±23.47） h， the complete fever reduction time （21.37±30.06）h， and the 24 h， 48 h， 72 h， fever reduction rate was 77.14%， 88.57%， 91.42% respectively. The above indicators of the control group showed as （17.58±20.38）h， （24.30±21.87）h， 61.29%， 90.32%， 96.77% respectively， with no statistically significant differences （P＞0.05）. On the 7th day after treatment， the total score of TCM syndromes in trial group and control group decreased compared to those before treatment （P＜0.05）. There was no statistically significant difference in the cure rate， significant effective rate， effective rate， and total effective rate of TCM syndromes between groups （P＞0.05）. On the 4th day， the lymphocyte ratio of patients in the control group was higher than before treatment， while alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， urea， and creatinine of both groups before and after treatment were within the normal range. The main adverse reactions in both groups were mild headache and dizziness， and no serious adverse reactions observed. ConclusionThe therapeutic effect of Qiaoqi Formula in treating mild influenza is equivalent to Lianhua Qingwen Capsules， which can shorten the fever reduction time， improve clinical symptoms， and no adverse events observed during the study.

Objective To explore the prognostic value of hs-cTnⅠ in patients with suspected acute coronary syndrome(ACS)in emergency department.Methods A large-scale,prospective observa-tional study was conducted on totally 966 patients with suspected ACS admitted in Fuwai Hospi-tal from January 2017 to October 2020.Their baseline serum/plasma hs-cTnⅠ level was detected at admission,conventional treatment was performed,and relevant data were collected.Logistic regression analysis was used to predict the risk of primary and secondary endpoint events within 30 d by hs-TnⅠ concentration,and subgroup analysis was performed.Results Among the 966 patients,the time from chest pain to visit was 5.0(2.5,13.0)h,and 284 patients had primary end-point events within 30 d,including 283 cases of myocardial infarction(99.6％)at the first visit,1 case of recurrent myocardial infarction(0.4％),5 cases of cardiovascular death(1.8％),and 1 case of unplanned revascularization(0.4％).When hs-cTnⅠ was at the minimum detection limit of 2 ng/L,the incidence of adverse events was 5.8％,when the limit of 70 ng/L,the incidence was 49.2％,and when of 316 ng/L,the incidence reached 100％.The model could correctly classify 92.3％of the patients.Conclusion The hs-cTn sequence has a good predictive effect for the risk of short-term cardiovascular adverse events in Chinese population.