The association between heavy metal exposure and erectile dysfunction in the United States / 亚洲男科学杂志(英文版)

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.

Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis / 中国当代儿科杂志

OBJECTIVES@#To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis.@*METHODS@#Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue.@*RESULTS@#The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05).@*CONCLUSIONS@#In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

Clinical Study of Osteoking Combined with Non-Steroidal Anti-inflammatory Drugs in Treatment of Knee Osteoarthritis / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis based on real-world data and provide a basis for clinical medication. MethodFrom May 2020 to December 2021， the data of a total of 1 002 patients with knee osteoarthritis who did not undergo knee joint replacement surgery was collected through the registration method. 952 patients were ultimately included， including 133 cases orally taking Osteoking combined with non-steroidal anti-inflammatory drugs as the observation group and 73 cases orally taking non-steroidal anti-inflammatory drugs alone as the control group. Statistical analysis was conducted on the baseline data， VAS scores， WOMAC scores， and other items. The visit point is the 4th and 8th weeks after registration. In order to further elucidate the clinical efficacy of Osteoking combined with non-steroidal anti-inflammatory drugs in the treatment of knee osteoarthritis， the effective components of Osteoking and the relevant gene sets of non-steroidal anti-inflammatory drugs and knee osteoarthritis were obtained through network pharmacology methods and retrieval in bone injury cross database， TCMSP， and other databases. Venn analysis was performed on the relevant gene sets， and a PPI network diagram was constructed. Then key core targets were screened out， and enrichment GO and KEGG enrichment analyses were conducted. ResultThe VAS score of the observation group decreases by an average of （-2.79±1.206） scores in the 4th week， which is better than the control group ［（-2.73±1.575） scores， P<0.05］. The VAS score of the observation group decreases by an average of （-3.97±1.308） scores in the 8th week， which is better than the control group ［（-3.89±1.822） scores， P<0.05］. The total WOMAC score of the observation group decreases by an average of （-52.07±21.677） scores points in the 8th week， which is significantly better than the control group ［（-46.75±25.368） scores， P<0.05］. The observation group has an average decrease of （-10.99±4.229） scores in WOMAC （pain） score in the 8th week， which is better than the control group ［（-10.03±5.535） scores， P<0.05］. The observation group has an average decrease of （-1.49±2.901） in WOMAC （stiffness） score in the 4th week， which is better than the control group ［（-0.92±1.998） scores， P<0.05］， and the observation group has an average decrease of （-1.90±3.200） scores in WOMAC （stiffness） score in the 8th week， which is better than the control group ［（-1.26±2.230） scores， P<0.05］. The observation group shows an average decrease of （-39.17±16.562） scores in WOMAC （joint function） score in the 8th week， which is significantly better than the control group ［（-35.47±20.098） scores， P<0.05］. According to network pharmacology analysis， the core network target of Osteoking in treating knee osteoarthritis is manifested as regulating signal pathways such as signal transduction transcription activator 3（STAT3）， vascular endothelial growth factor A（VEGFA）， tumor necrosis factor （TNF） to regulate cell signaling， angiogenesis， chondrocyte proliferation and migration， and inflammatory cells， thereby inhibiting inflammatory reactions， reducing damage， and delaying the development of the disease. ConclusionAfter a 4-week and 8-week course of treatment for knee osteoarthritis with Osteoking combined with non-steroidal anti-inflammatory drugs， there is a significant therapeutic effect on relieving pain and joint stiffness and improving joint function. In network pharmacology， Osteoking is involved in regulating inflammatory factors， metabolic response-related biological processes， the proliferation and apoptosis of chondrocytes， etc. in the treatment of knee osteoarthritis， resulting in anti-inflammatory and analgesic effects and improving joint mobility and joint stiffness. Therefore， it is worthy of clinical promotion and application.

A Real-World Clinical Study of Osteoking Combined with Intra-Articular Injection of Sodium Hyaluronate in Treatment of Knee Osteoarthritis / 中国实验方剂学杂志

ObjectiveTo investigate the improvement of the efficacy of Osteoking in patients with knee osteoarthritis in the onset and remission stage and to systematically explore its potential intervention mechanism， so as to provide a certain reference for improving the clinical application value of Osteoking and guiding its clinical rational drug use. MethodThrough the real-world study of the treatment of knee osteoarthritis with Osteoking， the data was obtained and entered into the "Osteoking for the treatment of knee osteoarthritis case registration system"， and 105 patients with episodic and remission knee osteoarthritis from the outpatient or inpatient orthopedic department of 20 medical institutions， including the Third Affiliated Hospital of Beijing University of Chinese Medicine， Peking Union Medical College Hospital， Wangjing Hospital of the Chinese Academy of Chinese Medical Sciences and Hunan Aerospace Hospital， from May 1， 2020 to December 31， 2021， were selected in the system. It included 60 patients treated with Osteoking and joint injection， and 45 patients treated with joint injection alone. The WOMAC osteoarthritis index score， visual analogue （VAS） pain score， individual types of pain symptoms （cold pain， hot pain， tingling， dull pain， soreness） and other TCM symptoms were observed and compared between the two groups， and statistically analyzed. In order to further elucidate the potential molecular mechanism of Osteoking combined with joint injection in the treatment of knee osteoarthritis in the treatment of onset and remission， this study used the "Bone Injury Cross Database （http：//bone-xtrans.com/database，BX-Data）" to collect the gene set of knee osteoarthritis disease， the traditional Chinese medicinal materials， chemical composition， material base， candidate target， candidate target， sodium hyaluronate candidate target data for screening， and constructed an interaction network of "disease target". ResultsAmong the 105 patients with knee osteoarthritis enrolled， 15.24% （16/105） were in the episodic period， 84.76% （89/105） were in remission， and there were no convalescent patients. There were 72 cases （68.57%） in women， 33 cases （31.43%） more than men， 60 cases in the observation group and 45 cases in the control group in 105 patients. There were 20 patients with a VAS score of 5 and 19 patients with a score of 6 in the observation group， accounting for 65.00% of the observation group. The comparative results of VAS scores between groups before and after treatment showed that the scores of the two groups were （4.42±1.01） scores， （5.00±1.02） scores.4 weeks after treatment， and （3.12±1.04） scores and （3.56±1.08） scores，8 weeks after treatment， respectively， which were lower than those before treatment （6.23±1.28） scores，（ 6.02±1.22） scores （P<0.05）， and the comparative results of the pain properties of the two groups showed that the improvement rates before and after thermal pain and tingling in the observation group were 3.3%（2/60） and 16.7%（10/60）， respectively. The control group was 2.2% （1/45）and 15.6%（7/45）［（χ2=4.034、13.583，P<0.05）］， respectively， and the improvement rate of cold pain and soreness in the observation group was 5.0%（3/60） and 3.3%（2/60）， which was higher than that of the control group . The results of comparing the WOMAC scores before and after treatment of the two groups showed that the difference between the stiffness score before and after treatment in the observation group was （1.68±1.42） scores， the difference between the score before and after treatment in the control group was （1.20±1.60） scores （P<0.05）， and the pain score before and after treatment was （3.43±2.88） scores， the difference before and after daily activity score was （12.37±10.21） scores， and the total score before and after treatment was （17.48±12.76） scores， which were also higher than those in the control group （2.82±3.29）， （10.80±9.63），（14.82±12.62） scores. The results of comparing the improvement of other symptoms before and after treatment showed that the improvement rate of less sleep and more dreams in the observation group was 28.3%（17/60）， which was significantly higher than that of the control group of 2.2%（1/45）（χ2=5.914，P<0.05）， and the improvement rates of the five symptoms of thirst and drinking， irritability， dry mouth and pharynx， dull complexion and hand， foot and mouth fever in the observation group were 3.3%（2/60）， 10.0%（6/60）， 8.3%（5/60）， 10.0%（6/60） and 5.0%（3/60）， respectively， which were higher than those in the control group -2.2%（1/45）， 2.2%（1/45）， 2.2%（1/45）， 4.5%（2/45）， -6.7%（3/45）. Through network analysis， it was found that the enrichment pathway of Henggu bone wound healing agent mainly acted on the three mechanisms of bone improvement， energy metabolism and anti-inflammatory and analgesic， and the sodium hyaluronate enrichment pathway mainly acted on the anti-inflammatory and analgesic mechanism. ConclusionThe efficacy of Osteoking combined with intra-articular injection of sodium hyaluronate in the treatment of patients with knee osteoarthritis in attack and remission is better than that of sodium hyaluronate alone， especially in anti-inflammatory and analgesic， and the two drugs have synergistic effect. Osteoking may play its role in relieving the symptoms of joint stiffness， tingling， heat pain， and less sleep and more dreams by improving bone quality and regulating the body's energy metabolism pathways， which is worthy of clinical promotion.

Clinical Efficacy and Mechanism of Osteoking in Treatment of Knee Osteoarthritis Based on Real-world Data / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy and mechanisms of Osteoking in the treatment of knee osteoarthritis （KOA） in real-world practice， so as to provide a basis for the rational clinical use of Osteoking. MethodFrom the Osteoking for knee osteoarthritis case registration system， 638 KOA cases treated with Osteoking were selected and analyzed in SPSS 26.0. The clinical data were collected from 20 hospitals in China from May 2020 to December 2021. Descriptive analyses of patient age， gender， body mass index， course of treatment and other parameters were performed. The Mann-Whitney U test was performed to compare the visual analogue scale （VAS） and Western Ontario and McMaster universities arthritis index （WOMAC） scores before and after treatment. The integrative pharmacology-based research platform of traditional Chinese medicine （TCMIP） v2.0 was used for network analysis of the core targets of Osteoking in treating knee osteoarthritis. Furthermore， 20 KOA patients treated with Osteoking in the Third Affiliated Hospital of Beijing University of Chinese Medicine from October to December in 2022 were enrolled in the treatment group， and 20 healthy volunteers in the control group. The enzyme-linked immunosorbent assay was employed to measure the serum levels of related indicators to verify the prediction results. ResultA total of 638 KOA patients were treated with Osteoking， including 429 （67.24%） receiving Osteoking alone and 209 （32.76%） receiving Osteoking combined with other therapies. The female patients （415， 65.05%） were more than the male patients （223， 34.95%）. The patients showed the mean age of （63.48±13.51） years， mean body mass index of （24.09±2.98） kg·m-2， and mean course of treatment of （15.78±9.66） days. Most of the patients were rated as grades Ⅱ （46.24%） and Ⅲ （34.64%） in Kellgren-Lawrence （K-L） grading and in the relief stage （82.45%） in clinical staging. There was no significant correlation between clinical staging and K-L grading results. The cluster analysis identified three TCM syndromes： Qi stagnation and blood stasis， cold-dampness obstruction， and liver-kidney deficiency. The overall clinical efficacy evaluation showed that VAS score decreased from （6.01±0.85） scores before treatment to （2.54±1.73） scores after treatment （P<0.05）， and the WOMAC score decreased from （93.25±25.91） scores before treatment to （50.73±25.14） scores after treatment （P<0.05）. The network analysis predicted that Osteoking might regulate the transforming growth factor-beta （TGF-β）， tumor necrosis factor-alpha （TNF-α）， and nuclear factor-kappa B （NF-κB） signaling pathways to exert the therapeutic effect. The clinical trial showed elevated TGF-β1 level （P<0.01） and lowered NF-κB subunit RELA and tumor necrosis factor receptor superfamily， member 1A （TNFRSF1A） levels （P<0.05） after treatment. The synergistic effects of these changes provide a multidimensional and comprehensive therapeutic efficacy for KOA， alleviating the joint pain and limited mobility in patients. ConclusionOsteoking showed significant therapeutic efficacy in treating KOA. Osteoking may act on multiple pathways involved in cartilage metabolism and inflammation. The findings provide experimental evidence and theoretical support for elucidating the multi-target mechanism of Osteoking in treating KOA.

The rules of Traditional Chinese Medicine compounds for diabetes based on the National Patent Database / 国际中医中药杂志

Objective:To analyze the rules of Traditional Chinese Medicine (TCM) for treating diabetes based on the National Patent Database.Methods:In the patent search and analysis platform of the China National Intellectual Property Administration, search the invention patents of the TCM compounds for treating diabetes during January 1,2016-December 31,2020. The Ancient and Modern Medical Records Cloud Platform (V2.3.5) was used to conduct the statistics of Chinese materia medica frequency, the nature and meridian entry, and the analysis of association rules. The cluster analysis and factor analysis were carried out with the SPSS 25.0.Results:A total of 490 TCM compound patents were included, which involve 791 kinds of Chinese materia medica. For each patent, the number of the Chinese materia medica types was rough 13-14 in average. Remarkably, thirty kinds of Chinese materia medica with high frequencies were obtained, where tonic Chinese materia medica accounted for the largest number, followed by the heat-clearing Chinese materia medica. Among these Chinese materia medica the categories of nature are mainly flat, cold and slightly cold, while the flavors are mostly sweet, bitter and pungent, which mainly belongs to the three meridians of lung, kidney and spleen. As for the results of statistical analysis, the association rule analysis indicated that there were 17 effective kinds of Chinese materia medica pairs, such as Rhizoma Dioscoreae-Astragalus Membranaceus and Radix Rehmanniae Recen-Astragalus Membranaceus. Seven Chinese materia medica groups were derived by the cluster analysis, and 11 common factors were extracted through factor analysis. Conclusions:The TCM compounds for treating diabetes are based on clearing heat and moisturizing dryness, nourishing yin and fluid, supplemented by invigorating spleen and removing dampness, dispelling phlegm and dissolving blood stasis, purging fire and detoxification. Notably, in clinical application, phlegm, blood stasis, heat toxin and other pathological products are supposed to be the focus, must identifying the both symptoms and root causes.

Real-world Study of Medication Characteristics and Clinical Efficacy of Tenghuang Jiangu Tablets in Treatment of Knee Osteoarthritis in Remission Stage / 中国实验方剂学杂志

ObjectiveTo explore the medication characteristics and clinical efficacy of the Tenghuang Jiangu tablets in the treatment of knee osteoarthritis （KOA） in the remission stage in the real world，providing references for rational clinical use of this prescription. MethodBased on the "registration system of KOA treated with Tenghuang Jiangu tablets"，2 439 KOA cases in the remission stage were analyzed by SPSS 25.0，IBM SPSS Modeler18.0，and Apriori algorithm. To be specific，the age，body mass index （BMI），and course of treatment were described in the form of x̄±s. The information on gender，K-L grade，daily dose，and frequency of drug use was described by frequency analysis. The number of cases，course of treatment，daily dose，and drug use frequency of the single-use group and the combined-use group were described by frequency analysis，and the combination of drugs was described by frequency analysis and Apriori algorithm. Mann-Whitney U test was employed to compare the scores of Visual Analogue Scale （VAS），Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC），pain，stiffness，and joint function between the single-use group and the combined-use group. ResultThe results of clinical treatment showed that 2 439 patients with KOA in the remission stage were treated with Tenghuang Jiangu tablets，with 1 432 （58.71%） in the single-use group and 1 007 （41.29%） in the combined-use group. The average daily dose of Tenghuang Jiangu tablets was （3.90±1.44） g，and the majority of the patients were at grade Ⅱ （54.47%）. The daily average daily dose of Tenghuang Jiangu tablets in the single-use group was （3.64±1.35） g，which was lower than that in the combined-use group ［（4.26±1.48） g，P<0.05］. In the combined use，the top three western medicines were glucosamine （270 times，14.68%），sodium hyaluronate （126 times，6.85%），and imrecoxib （116 times，6.31%），and the top three Chinese medicines were Huoxuezhitong capsules/tablets/ointments （31 times，1.69%），Biqi capsules （25 times，1.36%），and Maizhiling （23 times，1.25%）. As for the overall clinical efficacy，the VAS score was （5.13±0.93） score before treatment and （2.22±1.18） score after treatment （P<0.05），with an overall average decrease of （2.91±1.14） score， and the average decrease in the single-use group was （2.76±1.43） score， which was lower than that in the combined-use group ［（3.12±1.36） score，（P<0.01）］. The WOMAC score was （31.05±11.84） score before treatment and （13.55±9.91） score after treatment （P<0.05）. The overall average decrease was （17.50±11.79） score， and the average decrease in the single-use group and combined-use group was （16.39±11.14） score and （19.08±12.50） score，respectively （P<0.01）. The patients with KOA>grade Ⅱ accounted for 91.34%（1 308/1 432） and 93.55%（942/1 007） in the single-use group and combined-use group，respectively （χ2=80.026，P<0.05）. A total of 43.37%（621/1 432） of the patients in the single-use group had other complications，lower than that in the combined-use group ［54.92%（553/1 432），（χ2=20.087，P<0.01）］. ConclusionMore than half of the patients with KOA in the remission stage are treated with Tenghuang Jiangu tablets alone，and the combination therapy is mainly applied in patients with severe conditions or other complications. In relieving knee joint pain and improving joint stiffness and joint function，both the Tenghuang Jiangu tablets alone and the combination therapy are effective.

Tenghuang Jiangu Tablets Combined with Non-steroidal Anti-inflammatory Drugs for Osteoarthritis of Knee： A Real-world Study / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Tenghuang Jiangu tablets （THJGT） combined with oral non-steroidal anti-inflammatory drugs （NSAIDs） in the treatment of osteoarthritis of the knee and its applicable stage based on real-world data， and provide a basis for the rational clinical use of THJGT. MethodA total of 218 cases treated with THJGT combined with oral NSAIDs included in the "THJGT for knee osteoarthritis case registry" from September 2019 to January 2021 were selected as the observation group， and 126 cases treated with oral NSAIDs alone as the control group （CG）. The data of gender， age， body mass index， Kellgren-Lawrence grading scale （K-L scale） score， visual analogue score （VAS score）， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， swelling grade， joint fear of cold score， back pain and weakness score， and occurrence of adverse events/reactions of the patients in both groups were used for the evaluation of efficacy with full analysis set. The propensity score matching method was used to exclude the influence of confounding factors between groups， and the sub-data sets were established， with which the repeated measures analysis of variance （ANOVA） was carried out to evaluate the efficacy. Visit points were at registration， 4 weeks and 8 weeks after registration. The data were statistically analyzed in Excel 2019 and SPSS 23.0. ResultThe proportion of females in the observation group was 66.06% （144/218）， which was higher than that （58.73%， 74/126） in the control group （χ2=1.846）. The average age in the observation group was （61.12±7.01） years， which was higher than that ［（59.38±5.99） years］ in the control group （W=19 918.50， P<0.05）. The remission rate in the observation group was 98.17% （214/218）. In the observation group， the proportions of the patients at K-L grades Ⅱ and Ⅲ were 64.22% （144/218） and 25.23% （55/218）， respectively. The effect analysis of the whole data set for enrollment and treatment for 8 weeks showed that the VAS score of the experimental group decreased by （3.27±1.24） points on average， which was better than that of the control group [（2.75±1.20）， W=34 179.00， P<0.05]. The average WOMAC score decreased （23.43±11.46） points， which was better than that of the control group [（16.71±8.86）， W=32 387.00， P<0.05]. The average swelling grade decreased （0.63±0.64）， which was better than the control group [（0.33±0.59）， W=33 847.50， P<0.05]. The average score of joint chills decreased （1.90±1.84）， points， which was better than that of control group [（1.40±1.28）， W=35 165.00， P<0.05]. The average lumbar acid fatigue score decreased by （2.02±1.64） points, which was better than that of the control group [（1.10±1.28）， W=32 986.50， P<0.05]. Efficacy analysis of subdata sets for enrollment， 4 weeks of medication and 8 weeks of medication showed that VAS scores of both groups showed a downward trend after treatment， and the improvement of experimental group was more significant than that of control group at 4 weeks， with statistical significance （P<0.05）. After treatment， the total WOMAC score of both groups showed a downward trend， and the improvement of experimental groups was more significant at 4 weeks and 8 weeks （P<0.05）. After treatment， swelling， cold fear grade and lumbar acid fatigue score of both groups showed a decreasing trend,， and the improvement of experimental group was more significant at 8 weeks （P<0.05）. The therapeutic effect analysis of patients in the attack stage and remission stage of the experimental group showed that the total WOMAC score of the two groups showed a downward trend after treatment， and the trend was basically the same， and there was no statistical difference between the two groups at enrollment， 4 weeks after treatment， and 8 weeks after treatment （t=1.675， t=2.068， t=2.364）. The total WOMAC score of the patients in remission stage in the experimental group with K-L grading between grade 0 and grade Ⅲ had statistical significance at 4 weeks after treatment compared with the time of entry （P<0.05， P<0.01）. Group of adverse event rate was 4.13% （9/218）， lower than the control group 10.32% （13/126） （χ2= 5.109， P<0.05）. ConclusionThe population receiving THJGT combined with oral NSAIDs is mostly female， old， in remission， and with K-L grades Ⅱ and Ⅲ. THJGT can enhance the anti-inflammatory and analgesic effects of oral NSAIDs and keep the drug effect in improving joint function and alleviating fear of cold， swelling， and back pain and weakness. The drug combination can be applied to patients in both attack and remission， and the clinical application should take patient's disease stage and degree of osteoarthritis into account. Furthermore， the combination has the potential to reduce the incidence of adverse events caused by NSAIDs.

Data mining of medical rule in Lingnan TCM masters for treating Allergic rhinitis / 国际中医中药杂志

Objective:To analyze the characteristics of prescription about Lingnan Traditional Chinese Medicine (TCM) masters for Biqiu treatment based on data mining, so as to provide reference for the clinical practice and patent drug research and development of rhinorrhea in Lingnan district.Methods:By searching journal documents and medical records in CNKI, VIP, Wanfang, Chinese BioMedical Database (SinoMed) and Duxiu Data Retrieval Platform, we selected the articles and famous TCM medical records that met the criteria on the TCM medical rules of treating Biqiu. We screened database in strict accordance with inclusion and exclusion criteria and extracted prescription information from medical cases. The software Ancient and Modern Consilia Cloud Platform (V 1.5) was used for data mining analysis and medical case standardization, and SPSS Clementine 12.0 software were used to conduct frequency statistics, association analysis and cluster analysis of drugs in medical cases. Results:A total of 31 articles and 42 medical cases including 73 prescriptions were screened. The frequency results showed that there were 40 kinds of high frequency TCMs (frequency more than 5), mainly including drugs for benefiting the qi and strengthening the spleen, medicine to relieve cold and promote nasal passages, which was the same as the frequency statistics of the effects of herbal medicine. Seven drug groups were obtained by cluster analysis. The results of rule analysis showed that 16 association rules for drug pairs and 18 association rules for 3 TCMs pairs were obtained.Conclusions:While treating allergic rhinitis, Lingnan medical doctors focus on tonifying spleen qi, dispersing wind and cold, and promoting the nasal passages, which reflect the treatment theory of cultivating earth and generating gold, and attacking and tonifying. Lingnan medical doctors commonly used Guangdong medicinal herbs, which have distinct regional characteristics. The data mining methods can comprehensively summarize and explore the potential rules of Lingnan prominent practitioners' treatment of allergic rhinitis, and provide reference for guiding the treatment of congested nose and congested nose in TCM.

Preliminary study of fogging process for fixing high-concentration radioactive aerosol 131I contamination in a radiopharmaceutica production unit / 中国辐射卫生

Objective To prove the feasibility of a Fogging Process in fixing high-concentration radioactive aerosol 131I contamination. Methods High-concentration radioactive aerosol 131I contamination in an 131I-operating glovebox for radiopharmaceutical production was disposed by using fogging and fixing process. The aerosol 131I concentrations were detected and the results were analyzed. Results After a 120 minutes fixing, the 131I contamination in this glovebox reduced from(289 ± 9) DAC and (304 ± 6) DAC to (21.7 ± 2.0) DAC and (26.2 ± 1.8) DAC. After a 180 minutes fixing, the 131I contamination in this glovebox reduced from (259 ± 10) DAC to (1.80 ± 0.18) DAC. These results showed that no aerosol 131I contamination was raised again after 24-hours finishing this task. Conclusion Aerosol 131I concentration in a limited space could be controlled by using a fogging and fixing process, which could reduce the risk of internal exposure of staff. This process could be used by radiopharmaceutical production as an emergency management for dispose high-concentration radioactive aerosol 131I contamination.

Construction and verification of a new nomogram for predicting stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy at high altitude / 临床肝胆病杂志

ObjectiveTo investigate related factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and to establish a nomogram model for predicting the risk of stone recurrence after surgery based on independent risk factors. MethodsA retrospective analysis was performed for the clinical data of 144 patients with gallstones who underwent endoscopic minimally invasive gallbladder-preserving cholecystolithotomy in Qinghai University Affiliated Hospital from January 2012 to January 2018, and according to postoperative stone recurrence, the patients were divided into non-recurrence group and recurrence group. The chi-square test was used for comparison of categorical data between two groups. LASSO and logistic regression analyses were used to analyze independent risk factors for postoperative stone recurrence, and the corresponding nomogram prediction model was plotted according to regression coefficient. The calibration curve was plotted to evaluate the reliability of the predictive nomogram; Harrell consistency index was used to quantify the discriminatory performance of the predictive nomogram; the receiver operating characteristic (ROC) curve was used to evaluate the sensitivity, specificity, and area under the ROC curve (AUC) of this predictive nomogram. ResultsAll 144 patients underwent successful endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, among whom 14 patients (9.7%) experienced stone recurrence after surgery. The multivariate analysis showed that family history (odds ratio ［OR］= 3.245, 95% confidence interval ［CI］: 0.752-13567, P=0.104), regular diet (OR=3.752, 95% CI: 1.067-14.141, P=0.041), stone homogeneity (OR=5.871, 95% CI: 1636-25.390, P=0.010), and medication compliance (OR=0.225, 95% CI: 0.057-0.799, P=0.024) were independent risk factors for recurrence. The nomogram model had an index of concordance (C-index) of 0.835 (95% CI: 0.732-0.938) in the modeling sample and 0.7925 in the verification sample, suggesting that the nomogram model in this study had good accuracy and discrimination. The predictive nomogram had an AUC of 0.835, suggesting that this nomogram had a relatively high predictive value. ConclusionFamily history, regular diet, stone homogeneity, and medication compliance are independent risk factors for stone recurrence after endoscopic minimally invasive gallbladder-preserving cholecystolithotomy, and the nomogram constructed based on these independent risk factors may help to predict the risk of postoperative stone recurrence.

Hemolysin Sph2 from Leptospira interrogans amplified inflammatory response in murine macrophages J774A.1 through HMGB1 / 中华微生物学和免疫学杂志

Objective:To investigate the possible mechanism of high mobility group box-1 (HMGB1) in amplifing inflammatory responses in Leptospira interrogans hemolysin Sph2-treated J774A.1 macrophages. Methods:Recombinant Sph2 was incubated with J774A.1 macrophages. The damage of cell membrane was detected by lactate dehydrogenase(LDH) determination; the changes of cell structure were observed by cryo-electron microscope; ELISA was used to determine the expression of HMGB1. After the commercial recombinant HMGB1 was incubated with mouse J774A.1 macrophages, the phosphorylation of NF-κB, p38-MAPK and JNK signaling pathway wsa detected by Western blot, and the expression of IL-1β, IL-6, and KC (IL-8) was detected by ELISA.Results:Recombinant hemolysin rSph2 induced significant changes in the structures of J774A.1 cells, including nucleus disappearance, cell membrane structure damage, cell lysis and membrane swelling. The yields of LDH and HMGB1 also increased significantly. Phosphorylated-NF-κB, -p38-MAPK and -JNK were increased by HMGB1. The expression of IL-1β, IL-6 and KC in J774A.1 cells was up-regulated by HMGB1 and inhibited via inhibitors of NF-κB, p38-MAPK and JNK signal pathways.Conclusions:Hemolysin rSph2 damaged the membrane of J774A.1 cells, and induced the secretion of HMGB1. Secreted-HMGB1 might induce the expression of IL-1β, IL-6 and KC in J774A.1 cells via NF-κB, p38-MAPK and JNK signal pathways, thus amplifying the inflammatory responses caused by Sph2.

miR-199a-5p regulates DDR1 to inhibit proliferation and migration of human glioma cells / 中国药理学通报

Aim To investigate the effect of miR-199a-5p on the proliferation and migration of human glioma cells. Methods U251 cells were selected as experimental subjects to construct a U251 cell line overexpressing miR-199a-5p. The experiment was divided into; control group (U251 cells without transfection, Control), negative control group (transfected with empty vector plasmid U251 cells, NC) and experimental group (transfected with miR-199a-5p mature mimics, mimics). Real-time fluorescent quantitative PCR was used to detect the expression of miR-199a-5p in each group; CCK-8 was used to detect the proliferation of cells transfected with miR-199a-5p; the cell scratch test and Transwell migration test were used to detect the migration of U251 in each group; Western blot was applied to detect DDR1 expression; a U251 cell line overexpressing DDR1 was constructed to detect the effect of overexpression of DDR1 on the proliferation and migration of U251 cells transfected with miR-199a-5p. Results The level of miR-199a-5p in mimics group was significantly higher than that in control group (P < 0.01), the cell viability was reduced (P < 0.01), and the proliferation ability was weakened (P <0. 01). The expression of DDR1 in miR-199a-5p group cells was significantly reduced (P < 0. 01). Compared with mimincs group, the pcDNA3. 1-DDR1 transfected group could up-regulate DDR1 (P < 0. 01), increase cell viability, and promote cell proliferation (P < 0. 05 or P < 0. 01). Conclusions miR-199a-5p can down-regulate the expression of DDR1 and inhibit the proliferation and migration of human glioma cells.

Identification of a novel CHS1/LYST variant in a Chinese pedigree affected with Chediak-Higashi syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation.@*METHODS@#Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene.@*RESULTS@#The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree.@*CONCLUSION@#Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.

Identification of Sigma N signaling system target genes in Leptospira interrogans / 中华微生物学和免疫学杂志

Objective:To confirm the Sigma N transcription factor activity of a gene product encoded by LA2404 gene of Leptospira interrogans ( L. interrogans) and to identify the target genes of Sigma N signaling system. Methods:L. interrogans LA2404 gene and its regulated target genes were predicted using bioinformatic analysis according to the promoter sequence signature in Sigma N-regulated genes. A LA2404 gene-knockout (ΔLA2404) strain of L. interrogans was constructed based on homologous sequence recombinant of suicide plasmid. Real-time fluorescent quantitative RT-PCR (qRT-PCR) was used to detect the changes in the expression of target genes at mRNA level in the ΔLA2404 mutant. A prokaryotic expression system for LA2404 gene was established and the target recombinant protein rSigma N was extracted by Ni-NTA affinity chromatography. Gel electrophoresis mobility shift assay (EMSA) was used to screen out the target genes regulated by rSigma N. Results:Pathogenic L. interrogans serogroup Icterohaemorrhagiae serovar Lai strain Lai carried one Sigma N gene and 22 Sigma N promoter sequence-containing target genes. Qualitative examination of the ΔLA2404 mutant by microscopy revealed no defect in motility and appearance. Expression of LA1188, LA2306, LA3426, LA1968, LA1313, LA3806 and LA0773 genes at mRNA level in the ΔLA2404 mutant was significantly down-regulated ( P<0.05), but no significant changes in the expression of other target genes at mRNA level were detected. EMSA results confirmed that rSigma N could bind to the promotor sequences of the target genes mentioned above. Conclusions:Sigma N transcription factor was encoded by LA2404 gene. LA1188, LA2306, LA3426, LA1968, LA1313, LA3806 and LA0773 genes contained Sigma N promoter sequence and the expression of them was regulated by Sigma N signaling system.

Comparisons of the resting-state fMRI functional connectivity of the habenula in the first-episode current depression and remitted depression / 中华行为医学与脑科学杂志

Objective:To investigate the difference of functional connectivity(FC) between the habenula and other brain regions in the patients with first-episode current depression (fMDD) and remitted depression (rMDD).Methods:Thirty-five patients with first-episode current depression (fMDD), 35 patients with remitted depression (rMDD) and 30 healthy controls (HC) matched with gender, age and education years were scanned by resting-state fMRI. Hamilton Depression Scale (HAMD 17) was used to assess the severity of the patients. After preprocessing, seed-based FC analysis was performed on the habenula. Pearson correlation analysis was performed between the FC values and HAMD 17 and duration of disease. Results:(1) Compared with the HC group, FC decreased between the habenula and left middle occipital gyrus(l-MOG) in fMDD group (x, y, z=-48, -84, 3, t=-4.335, P<0.05), while FC increased between the habenula and left supramarginal gyrus (x, y, z=-66, -30, 36, t=4.876, P<0.05), left superior frontal gyrus(l-SFG) (x, y, z=-6, -33, 51, t=4.402, P<0.05), left inferior parietal lobe(l-IPL)( t=3.300, P<0.05) and right inferior parietal lobe(r-IPL) ( t=3.557, P<0.05) in fMDD group. Compared with the HC, FC decreased between the habenula and l-MOG (x, y, z=-48, -84, 3, t=-4.321, P<0.05) and left thalamus (x, y, z=-9, 3, 3, t=-3.971, P<0.05) in rMDD group, while FC increased between the habenula and left middle temporal gyrus(l-MTG)( x, y, z=-48, -39, 9, t=4.062, P<0.05), left supramarginal gyrus (x, y, z=-51, -15, 45, t=2.906, P<0.05), l-SFG (x, y, z=-24, -21, 39, t=3.044, P<0.05), l-IPL ( t=2.880, P<0.05) and r-IPL ( t=3.512, P<0.05) in rMDD group. (2) FC decreased in fMDD group between the habenula and right orbitofrontal cortex(r-OFC) ( t=-3.899, P<0.05) and l-MTG ( t=-4.023, P<0.05) than rMDD group, while FC increased between the habenula and left supramarginal gyrus ( t=4.157, P<0.05), l-SFG( t=3.327, P<0.05), left thalamus ( t=3.316, P<0.05) and l-IPL ( t=3.909, P<0.05) than rMDD group. (3)There was no significantly correlation between the HAMD 17 and the FC value changes among the different regions, and was marginal significantly correlation between duration of disease and the FC values from the habenula and l-MOG( r=0.328, P=0.063). Conclusion:Both fMDD and rMDD show abnormal FC between the habenula and default mode network, visual network and reward network, which may be related to the pathogenesis of depression. The FC of the habenula in rMDD still had not recovered to normal.

Lead sulfide quantum dots for the near-infrared IIb window fluorescence imaging of colon cancer / 药学学报

The near-infrared-IIb (NIR-IIb, 1 500-1 700 nm) window fluorescence with long emission wavelength has reduced light scattering and tissue auto-fluorescent background, achieving deep tissue imaging with high spatial resolution. Herein, we prepared an NIR-IIb fluorescent quantum dots (QDs) composed of lead sulfide (PbS). The fluorescence spectrum of PbS QDs were adjusted by controlling the size of the PbS core. Cadmium sulfide (CdS) shell was synthesized by the cation exchange method to form the core/shelled lead sulfide/cadmium sulfide quantum dots (CSQDs). The surface of CSQDs was modified with polyethylene glycol (PEG) to increase their stability in aqueous solution. The resulting PEG-modified CSQDs (PEG-CSQDs) had the emission peak at ~1 550 nm with quantum yield of 7.2%. The animal procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of Fudan University School of Pharmacy. At 2 h postinjection, PEG-CSQDs clearly delineated the tumor region of mice bearing orthotopic CT26-Luc colon cancer model in the NIR-IIb fluorescence imaging. The fluorescent intensity ratio of primary tumor and adjacent normal tissue was 42.3, and that of metastatic tumor and adjacent normal tissue was 22.3, which allowed to detect the primary tumor of 3.4 mm×2.5 mm in dimension and the metastatic tumor of 1.2 mm×0.9 mm in dimension, and accurately guided the excision of tumors. The PEG-CSQDs prepared in this study provided a new approach for the early diagnosis and guidance of surgical resection of colon cancer.

Characterization of myelin oligodendrocyte glycoprotein (MOG)35-55-specific CD8+ T cells in experimental autoimmune encephalomyelitis / 中华医学杂志(英文版)

BACKGROUND@#The pathogenesis of multiple sclerosis (MS) is mediated primarily by T cells, but most studies of MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have focused on CD4 T cells. The aims of the current study were to determine the pathological interrelationship between CD4 and CD8 autoreactive T cells in MS/EAE.@*METHODS@#Female C57BL/6 mice (n = 20) were induced by myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. At 14 days after immunization, T cells were isolated from the spleen and purified as CD4 and CD8 T cells by using CD4 and CD8 isolation kits, and then the purity was determined by flow cytometric analysis. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. The interferon-gamma (IFN-γ) and interleukin (IL)-4 secretion of supernatant of cultured CD4 and CD8 T cells were measured by enzyme-linked immunosorbent assays (ELISA). For adoptive transfer, recipient mice were injected with MOG35-55-specific CD8 or CD4 T cells. EAE clinical course was measured by EAE score at 0-5 scale and spinal cord was examined by staining with hematoxylin and eosin and Luxol fast blue staining.@*RESULTS@#CD8CD3 and CD4CD3 cells were 86% and 94% pure of total CD3 cells after CD8/CD4 bead enrichment, respectively. These cells were stimulated by MOG35-55 peptide and applied to proliferation assays. Although the CD8 T cells had a generally lower response to MOG35-55 than CD4 T cells, the response of CD8 T cells was not always dependent on CD4. CD8 T cell secreted less IFN-γ and IL-4 compared with CD4 T cells. EAE was induced in wildtype B6 naïve mice by adoptive transfer of MOG35-55-specific T cells from B6 active-induced EAE (aEAE) mice. A similar EAE score and slight inflammation and demyelination were found in naive B6 mice after transferring of CD8 T cells from immunized B6 mice compared with transfer of CD4 T cells.@*CONCLUSION@#Our data suggest that CD8 autoreactive T cells in EAE have a lower encephalitogenic function but are unique and independent on pathogenic of EAE rather than their CD4 counterparts.

Analysis on regularity of traditional Chinese patent medicine in treating hyperlipidemia / 中国中药杂志

To explore the regularity of traditional Chinese patent medicines for the treatment of hyperlipidemia recorded in Newly Edited National Chinese Traditional Patent Medicines,the Composition Principles of Chinese Patent Drugs,New Drug Conversion Standard,the Compilation of National Standard for Traditional Chinese Medicines and Chinese Pharmacopoeia. Researchers extracted the information of prescriptions from these cases according to the inclusion and exclusion criteria. Then microsoft excel 2010 was used to conduct frequency statistics and count the frequency of traditional Chinese medicine. SPSS Clementine( ver.12. 0) and SPSS( ver. 18. 0)were adopted respectively for frequency analysis,association rules analysis,cluster analysis and factor analysis. Besides,KMO test and Bartlett spherical test were performed for factor adaptation test. Finally,a total of 173 traditional Chinese medicines were included,involving 94 Chinese patent medicine prescriptions. The frequency results of traditional Chinese medicine showed that there were 33 kinds of high-frequency traditional Chinese medicine,mainly including those for tonifying medicine,activating blood and resolving stasis and blood-stasis,and clearing damp. The association rules analysis found out 12 association rules of drug pairs,3-herb pairs of 25 and4-herb pairs of 6. Totally 11 medicine groups with relevance were respectively extracted by cluster analysis. KMO test and Bartlett spherical test indicated that the method was suitable for factor analysis and 11 common factors were respectively extracted by factor analysis. The association rules reflected the therapeutic method for tonify the liver and kidney,activating blood and resolving stasis. Cluster analysis and factor analysis showed the therapeutic method of Qi-enriching and Yin-nourishing,and the factor analysis focused more on removing blood stasis and dampness. The decision tree with hawthorn as the dependent variable reflects the importance of alisma orientalis and fructus schisandrae in the drug matching. In conclusion,data mining technique can comprehensively analyze the regularity of prescriptions of traditional Chinese patent medicine for hyperlipidemia,and is helpful for guiding the development of Chinese patent medicines and the clinical practice of traditional Chinese medicine.

Methylation of forkhead box protein 3 gene promoter in CD4+ T cells in patients with chronic hepatitis B / 中华实验和临床病毒学杂志

Objective@#To investigate the methylation status and expression of FOXP3 in CD4+ T cells of patients with chronic hepatitis B (CHB).@*Methods@#Peripheral blood mononuclear cells (PBMCs) from 59 CHB patients and 22 healthy controls (HC) were collected. The percentage of CD4+ CD25+ Foxp3+ Tregs in CD4+ T cells was estimated by flow cytometry. FOXP3 expression was measured by quantitative real time-polymerase chain reaction (RT-qPCR) and Western blotting. The methylation status of FOXP3 was determined by methylation-specific polymerase chain reaction.@*Results@#The percentage of CD4+ CD25+ pFoxp3+ Tregs in CD4+ T cells, FOXP3 mRNA and protein expression levels were significantly higher in patients with CHB than HCs (P<0.05). Meanwhile, the methylation frequency of FOXP3 was significantly lower in CHB patients than HCs (P<0.05). FOXP3 mRNA levels and the percentage of CD4+ CD25+ Foxp3+ Tregs were significantly lower (P<0.05) in patients with gene methylation than those without.@*Conclusions@#Aberrant demethylation of FOXP3 gene existed in CD4+ T cells of CHB, which contributed to an elevation in FOXP3 expression and percentage of CD4+ CD25+ Foxp3+ Tregs. It might provide a new target for prevention and treatment of CHB.