Relationship between plasma exosomal miR-346 and treatment outcomes in patients with multidrug resistant pulmonary tuberculosis / 中国热带医学

@#Abstract： Objective　To investigate the relationship between plasma exosomal microRNA (miRNA)-346 and treatment outcomes in patients with multidrug-resistant tuberculosis (MDR-TB), to provide more reference basis for the treatment of MDR-TB patients. Methods　A total of 406 patients with MDR-TB admitted to Tuberculosis Control and Prevention Institute of Shaanxi Provincial between January 2018 and May 2021 were selected as the study subjects. General clinical data of the patients were collected and analyzed. The expression level of plasma exosomal miR-346 was detected by real-time fluorescence quantitative polymerase chain reaction. The predictive value of plasma exosomal miR-346 for treatment outcome was analyzed using receiver operating characteristic (ROC) curve analysis. Furthermore, the relationship between the expression of plasma exosomal miR-346 and treatment outcome was analyzed using a multivariable logistic regression model. After standard treatment, patients were divided into good treatment outcome group (n=226) and poor treatment outcome group (n=180) according to the treatment outcome. Results　Typical exosomes were identified by transmission electron microscopy, particle size analysis and Western blot, that is, plasma exosomes were successfully extracted. In the poor treatment outcome group, more patients were complicated with diabetes or HIV infection, and the proportion of patients with pulmonary cavity, acid-fast bacilli smear positive rate >1+, previous treatment history and fluoroquinolone resistance was also significantly increased, and the levels of white blood cells, neutrophils, and monocytes were significantly increased, while the level of albumin was significantly decreased, with statistical significance (P>0.05). Compared with the good treatment outcome group [0.61 (0.46, 0.74)], the expression level of plasma exosomal miR-346 in the poor treatment outcome group [1.23 (0.60, 2.02)] was significantly higher (Z=-13.185, P<0.001). ROC curve analysis showed that the area under the curve of plasma exosomal miR-346 to predict adverse outcomes of MDR-TB treatment was 0.881 (95%CI: 0.846-0.915), with a sensitivity of 78.3% and specificity of 86.7%. The corresponding cut-off value was 0.81. Multivariate logistic regression analysis showed that diabetes, AIDS virus infection, pulmonary cavity, AFB smear positive degree>1+, previous treatment history, fluoroquinolones resistance and high expression of plasma exosomal miR-346 were independent influencing factors for poor treatment results of MDR-TB (P<0.05). Conclusions　High expression of plasma exosomal miR-346 is associated with the high risk of adverse outcome of MDR-TB treatment, and it is promising to be a useful marker for predicting the outcome of MDR-TB treatment.

Mechanism of electroacupuncture regulating the ligand pathway of tyrosine kinase receptor in improving vascular dementia / 解剖学报

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Establishment and verification of method for detection of hydrogen sulfide in organs by fluorescent probe method / 中国药理学通报

Aim To rapidly prepare and purify hydrogen sulfide specific fluorescent probe (WSP-5), establish and optimize the fluorescent probe method for the determination of hydrogen sulfide in animal tissues, and verify the applicability of the method in the model of malignant pleural effusion. Methods The preparation solvent of fluorescent probe reaction solution, DMSO addition volume, pH, reaction solution solvent and reaction solution volume, sample pretreatment temperature, grinding times, and standing time after grinding were investigated. The mouses model of malignant pleural effusion was established with S-180 ascites tumor cells, and the concentration of hydrogen sulfide in various organs and tissues of the model animal was measured. Results After optimization, silica gel and dextran gel were used as stationary phases, dichloromethane methanol formic acid (60: 1: 0.1, V/V/V) and dichloromethane methanol (1: 1, V/V) were used as eluents for separation and purification, and the first eluting component was taken to prepare WSP-5 with a purity of more than 700 mg. Animal tissue samples and sodium hydrosulfide standard solution were added with 5 times of cold reaction solution, after low temperature vibration grinding, highspeed centrifugation, the supernatant was incubated in dark for 12 hours, the fluorescence intensity was measured by fluorescent microplate reader. Hydrogen sulfide concentration was calculated according to the standard curve. The LOD of this method was about 0. 6 |JLmol • L

Efficacy evaluation of camrelizumab combined with apatinib in the treatment of primary hepatocellular carcinoma / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：重新评价卡瑞利珠单抗联合阿帕替尼治疗原发性肝癌（PHC）的有效性和安全性。方法：回顾性收集2019年1月至2021年5月在安徽医科大学附属第一医院确诊的PHC患者的临床资料。所有患者均接受卡瑞利珠单抗200 mg q3w联合阿帕替尼250 mg qd×21 d治疗。应用卡方检验进行基线特征比较，采用Kaplan-Meier法进行生存分析，从中估计中位总生存期（OS），然后采用Log-Rank检验进行比较；采用单因素Cox回归分析预测影响OS的因素。结果：本研究共纳入43例PHC患者，一线治疗患者的客观缓解率（ORR）为23.3%（7/30），二线及以上治疗患者的ORR为15.4%（2/13）。两组患者的疾病控制率（DCR）分别为83.3%（25/30）和61.5%（8/13），中位无进展生存期（PFS）分别为5.0个月（95% CI 3.2，6.8）和4.0个月（95% CI 1.7，6.3）（P=0.514），中位OS分别为13.0个月（95% CI 11.2，14.8）和9.0个月（95% CI 2.8，15.2）（P=0.179）。在43例患者中，33例（76.7%）存在3级或以上的治疗相关不良反应（AE）；最常见的AE为血小板计数下降（14.0%）、高血压（9.3%）和蛋白尿（9.3%）。Cox单因素回归分析显示，Child-Pugh分级是影响PHC患者预后的独立危险因素[HR=0.324，95% CI （0.146，0.716），P<0.05]。结论：卡瑞利珠单抗联合阿帕替尼可显著改善PHC患者的OS、ORR和DCR，AE可控。

Physiological and biochemical mechanisms of brassinosteroid in improving anti-cadmium stress ability of Panax notoginseng / 中国中药杂志

In this study, the effect of brassinosteroid(BR) on the physiological and biochemical conditions of 2-year-old Panax notoginseng under the cadmium stress was investigated by the pot experiments. The results showed that cadmium treatment at 10 mg·kg~(-1) inhibited the root viability of P. notoginseng, significantly increased the content of H_2O_2 and MDA in the leaves and roots of P. noto-ginseng, caused oxidative damage of P. notoginseng, and reduced the activities of SOD and CAT. Cadmium stress reduced the chlorophyll content of P. notoginseng, increased leaf F_o, reduced F_m, F_v/F_m, and PIABS, and damaged the photosynthesis system of P. notoginseng. Cadmium treatment increased the soluble sugar content of P. notoginseng leaves and roots, inhibited the synthesis of soluble proteins, reduced the fresh weight and dry weight, and inhibited the growth of P. notoginseng. External spray application of 0.1 mg·L~(-1) BR reduced the H_2O_2 and MDA content in P. notoginseng leaves and roots under the cadmium stress, alleviated cadmium-induced oxidative damage to P. notoginseng, improved the antioxidant enzyme activity and root activity of P. notoginseng, increased the content of chlorophyll, reduced the F_o of P. notoginseng leaves, increased F_m, F_v/F_m, and PIABS, alleviated the cadmium-induced damage to the photosynthesis system, and improved the synthesis ability of soluble proteins. In summary, BR can enhance the anti-cadmium stress ability of P. notoginseng by regulating the antioxidant enzyme system and photosynthesis system of P. notoginseng under the cadmium stress. In the context of 0.1 mg·L~(-1) BR, P. notoginseng can better absorb and utilize light energy and synthesize more nutrients, which is more suitable for the growth and development of P. notoginseng.

Prediction of coronary artery lesions based on C-reactive protein levels in children with Kawasaki Disease: a retrospective cohort study

Abstract Objective Since coronary artery lesions (CALs) are the most severe complication of Kawasaki disease (KD), clinically speaking, early prediction of CALs is crucial. The authors aimed to investigate the predictive value of C-reactive protein (CRP) in predicting CALs in KD patients. Methods KD patients were divided into the CALs group and the non-CALs group. The clinical and laboratory parameters were collected and compared. Multivariate logistic regression analysis was used to determine the independent risk factors of CALs. The receiver operating characteristic curve was applied to determine the optimal cut-off value. Results 851 KD patients who met the inclusion criteria were studied, including 206 in the CALs group and 645 in the non-CALs group. Children in the CALs group had significantly higher CRP levels than the non-CALs group (p< 0.05). Multivariable logistic regression analysis showed that incomplete KD, male, lower hemoglobin, and higher CRP were independent risk factors for predicting CAL (all p< 0.05). The optimal cut-off value of initial serum CRP for predicting CALs was 105.5 mg/L, with a sensitivity of 47.57% and a specificity of 69.61%. In addition, KD patients with high CRP (≥105.5 mg/L) had a higher occurrence of CALs than those with low CRP (<105.5 mg/L) (33% vs 19%, p< 0.001). Conclusion The incidence of CALs was significantly higher in patients with high CRP. CRP is an independent risk factor for CALs formation and may be useful for predicting CALs in KD patients.

Screening of quality markers and activity verification of Glycyrrhizae Radix et Rhizoma based on small molecule compound-protein interaction / 中国中药杂志

In order to solve the problem of weak correlation between quality control components and efficacy of Glycyrrhizae Radix et Rhizoma, this study detected the interaction between small molecular chemical components of Glycyrrhizae Radix et Rhizoma and total proteins of various organs of mice by fluorescence quenching method to screen potential active components. The 27 chemical components in Glycyrrhizae Radix et Rhizoma were detected by HPLC and their deletion rates in 34 batches of Glycyrrhizae Radix et Rhizoma were calculated. Combined with the principle of component effectiveness and measurability, the potential quality markers(Q-markers) of Glycyrrhizae Radix et Rhizoma were screened. RAW264.7 macrophage injury model was induced by microplastics. The cell viability and nitric oxide content were detected by CCK-8 and Griess methods. The levels of inflammatory factors(TNF-α, IL-1β, IL-6, CRP) and oxidative stress markers(SOD, MDA, GSH) were detected by the ELISA method to verify the activity of Q-markers. It was found that the interaction strength between different chemical components and organ proteins in Glycyrrhizae Radix et Rhizoma was different, reflecting different organ selectivity and 18 active components were screened out. Combined with the signal-to-noise ratio of the HPLC chromatographic peaks and between-run stability of the components, seven chemical components such as liquiritin apioside, liquiritin, isoliquiritin apioside, isoliquiritin, liquiritigenin, isoliquiritigenin and ammonium glycyrrhizinate were finally screened as potential Q-markers of Glycyrrhizae Radix et Rhizoma. In vitro experiments showed that Q-markers of Glycyrrhizae Radix et Rhizoma could dose-dependently alleviate RAW264.7 cell damage induced by microplastics, inhibit the secretion of inflammatory factors, and reduce oxidative stress. Under the same total dose, the combination of various chemical components could synergistically enhance anti-inflammatory and antioxidant effects compared with the single use. This study identified Q-markers related to the anti-inflammatory and antioxidant effects of Glycyrrhizae Radix et Rhizoma, which can provide a reference for improving the quality control standards of Glycyrrhizae Radix et Rhizoma.

Neutral wedge osteotomy assisted by determination of the center of rotation of angulation at the distal humerus anatomical axis for cubitus varus deformity in children / 中华创伤骨科杂志

Objective:To evaluate the clinical outcomes of neutral wedge osteotomy assisted by determination of the center of rotation of angulation (CORA) at the distal humerus anatomical axis for cubitus varus deformity in children.Methods:From 2016 to December 2019, 20 children with cubitus varus after supracondylar fracture of the humerus were treated at Department of Orthopeadics, Children's Hospital of Wujiang District. They were 8 boys and 12 girls, aged from 4 to 12 years (average, 7.0 years). Standard anteroposterior X-ray films of bilateral humerus were taken preoperatively for measurement of Baumann angle, proximal anatomical axis (PAA) and distal anatomical axis (DAA) of bilateral humerus to determine the CORA and the varus deformity angle. A lateral closed neutral wedge osteotomy was performed around the CORA to correct the varus deformity. All children were immobilized with elbow plaster cast after operation. Elbow flexion and extension function, postoperative scar, and body surface carrying angle were recorded. The carrying angle and Baumann angle were also measured on elbow X-ray films. Elbow function was evaluated according to the modified Flynn elbow score at 24 months after operation.Results:All patients were followed up for 24 to 36 months (mean, 29.3 months). Elbow hyperextension was close to normal in 18 cases, and 5° hyperextension existed in 2 cases. The flexion was greater than 130°, averaging 133.1° (from 130° to 138°), in 15 patients. The flexion ranged from 110° to 130° in 5 patients. The Baumann angle was 99.0°±1.0° preoperatively and 76.0°±1.0° postoperatively; the carrying angle was -14.0°±1.0° preoperatively and 13.6°±1.0° postoperatively. There were significant differences between the above items between preoperation and postoperation ( P<0.05). According to the modified Flynn elbow score at 24 months after operation, the elbow function was excellent in 16 and good in 4 cases. The varus of 40° was corrected during surgery in one child. Fixation failure or correction failure occurred in none of the children before removal of the plaster or the Kirschner wire. Conclusions:In neutral wedge osteotomy assisted by determination of the CORA at the distal humerus anatomical axis, the CORA and angulation of the distal humerus inversion can be accurately determined so that the osteotomy line and the angulation correction axis can pass through the CORA to restore the humerus alignment with no displacement of the broken ends.

Epidemiology and clinical characteristics of scrub typhus based on 680 unexplained fever patients in Hainan / 中国热带医学

@#Abstract: Objective　To analyze the epidemiological characteristics of scrub typhus in 680 patients with unexplained fever in Hainan Island and provide guidance for local scrub typhus prevention and control. Methods　Blood samples from patients with clinically diagnosed unexplained fever in the First Affiliated Hospital of Hainan Medical University, Second Affiliated Hospital of Hainan Medical University, Haikou Municipal People's Hospital and Central South University Xiangya Medical College Affiliated Hospital, People's Hospital of Qiongzhong Li Miao Autonomous County were collected between 2018 and 2021, then samples were tested for Orientia tsutsugamushi specific IgM, IgG antibodies and Orientia tsutsugamushi 56kD-specific antigen genes using colloidal gold immunochromatography and PCR methods. The clinical and epidemiological information of the samples were also collected. Epidemiological analysis was carried out on the obtained sample information and test results. Results　A total of 680 samples from patients with clinically unknown fever were collected. The positive rates of scrub typhus IgM antibody, IgG antibody, PCR were 23.97% (163/680), 36.62% (249/680), 20.88% (142/680), respectively, and eschar or rash was observed in 12.06% (82/680) of all patients. According to the diagnostic criteria, 223 patients were finally diagnosed with scrub typhus. Among them, there were 111 males (49.78%) and 109 females (48.88%); the average age was (53.14±15.12) years old, and the 40-<60 years old was the main incidence group (98 cases, accounting for 43.95%). The ethnicity of the patient with scrub typhus was mainly Han ethnicity (136 cases, accounting for 60.99%). Farmers were the main morbidity group (93 cases, 41.70%). The patient with scrub typhus distributed throughout the island except for Sanya and Wuzhishan, with Haikou and Qiongzhong show the highest number of cases. The number of cases in autumn was the highest (114 cases, 51.12%). The clinical manifestations of infected patients were mainly non-specific symptoms and signs, 36.77% of patients developed skin-specific ulcers or eschars, which were mainly distributed in the shoulder and neck, armpits, elbow fossa, chest and abdomen, back, buttocks, groin, scrotum and other joints and skin folds of the upper and lower limbs. Conclusions　Hainan Island is the foci of scrub typhus and the epidemic time has obvious seasonality. Its prevention should focus on rural areas in autumn, and its clinical features are mainly high fever and eschar or ulceration.

Retrospective Analysis of Hematological Phenotypes in Patients with Gene Mutation and Deletion α-Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To explore the differences between hematological phenotypes of patients with different genotypes in gene mutations and deletion α- thalassemia.@*METHODS@#By screening the α- thalassemia gene test results in the First Affiliated Hospital, Sun Yat-Sen University from January 2015 to April 2020, the patients with mutation and deletion α- thalassemia were obtained, then the differences between hematological phenotypes of patients with different genotypes were analyzed.@*RESULTS@#There were 96 patients with mutation combined with deletion α- thalassemia from the results of 24 054 α- thalassemia patients screened out, including 79 patients with non-deletion Hb H disease (α@*CONCLUSION@#The hematological phenotype changes caused by α

Acupoint catgut embedding inhibiting neuroinflammation in vascular dementia rats / 解剖学报

Objective To observe the effect of acupoint catgut embedding on the expression of inflammatory factor mRNA in cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signal pathway of vascular dementia (VD) rats, and to explore the protective mechanism of acupoint catgut embedding on the brain inflammatory response of VD rats. Methods VD model was established by the modified Pulsinelli ' s four vessel blocking method. Totally 148 male rats were randomly divided into VD model group, non acupoint catgut embedding group and acupoint catgut embedding group. On the 7th day after operation, catgut embedding at acupoints and catgut embedding at non acupoints were performed in the two treatment groups respectively, and materials were taken out 15 days later. Western blotting was used to detect the expression of COX-2 and PGE2, and real-time PCR was used to detect the mRNA expression of tumor necrosis factor α (TNF-α), intercellular cell adhesion molecule 1 (ICAM-1), interieukin(IL)-6, macrophage inflammatory protein 2 (MIP-2), IL-lβ, and monocyte chemotactic protein 1 ( MCP-1 ) in rat hippocampus. Results Compared with the sham group, the expressions of COX-2, PGE2, TNF-α, ICAM-1, IL-6, MIP-2, IL-lβ and MCP-1 in hippocampus of the other three groups were significantly higher (P<0.01). Compared with the model group, the expressions of COX-2, PGE2 protein and TNF-α, ICAM-1, IL-6, MIP-2, IL-lβ, MCP-1 mRNA in the hippocampus of the acupoint catgut embedding group and the non acupoint catgut embedding group decreased significantly (P<0.01). Conclusion Acupoint catgut embedding can protect the brain from inflammatory injury by down-regulating the expression of related inflammatory factors in COX-2/PGE2 signaling pathway and reducing the inflammatory response induced by VD rats.

Relationship between health risk behaviors and mental health of middle school students / 中国学校卫生

Objective@#To understand mental health status of middle school students in Weifang, and to analyze its association with health risk behaviors, and to provide a reference basis for the effective prevention of mental health problems.@*Methods@#Using the self-designed questionnaire and Kessler l0 (K10), a total of 3 185 middle school students in Weifang selected by using stratified clustered sampling were investigated. Chi-square test and binary Logistic regression was used for statistical analysis.@*Results@#Among the middle school students in Weifang, 1 634(51.3%) reported good mental health, 854(26.8%) in moderate level, 394(12.4%) reported poor mental health, and 303(9.5%) reported very poor mental health. Sleep duration and smoking were associated with mental health of middle school students (P<0.05). Logistic regression analyses showed that, compared with adolescents with sleep duration less than 8 h, mental health among students whose sleep duration ≥8 h was better(OR=0.36); compared with non-smokers, students who smoked showed worse mental health status (OR=3.53).@*Conclusion@#Health-risk behaviors are closely related to mental health of middle school students. Relevant departments should strengthen education and publicity of healthy lifestyles, and pay close attention to the impact of health risk behaviors on mental health.

Clinical value of PCR-flow Fluorescence Hybridization in Prenatal Genetic Diagnosis of Thalassemia / 中国实验血液学杂志

OBJECTIVE@#To explore the value of PCR-flow fluorenscence immunmicrobeads assay in prenatal gene diagnosis of thalassemia.@*METHODS@#A total of 1001 pregnant women and their couples checked in the First Affiliated Hospital of Sun Yat-Sen University from January 2016 to August 2019 were selected. Both pregnant women and their spouses were the carriers of thalassemia gene. Samples such as amniotic fluid, were used to extract genomic DNA at the right time. Parallel detection of α- and β- thalassemia genes to samples should be carried out by PCR-flow cytometric fluorescence hybridization and traditional multiple Gap-PCR and PCR-RDB techniques. The consistency of two methods in gene diagnosis of thalassemia was evaluated by analyzing the results of detection.@*RESULTS@#389 normal genotypes (38.86%, 389/1001) and 59 abnormal genotypes (61.14%, 612/1001) was cheked out by the two methods, including 416 cases of α-thalassemia, 162 cases of β-thalassemia and 34 cases of αβ- complex thalassemia. The main genotypes of α-thalassemia were --@*CONCLUSION@#Guangzhou is a area with high incidence of thalassemia, and the genetic types of thalassemia are complex and diverse. Prenatal diagnosis is the final barrier to the prevention of thalassemia. PCR flow-cytometric fluorescence hybridization, as a simple and fast technique, combined with traditional techniques in parallel contributed to the accuracy of prenatal gene diagnosis of thalassemia.

Comparison of medial-lateral pinning and lateral pinning for pediatric supracondylar humeral fractures: a Meta-analysis / 中国医师进修杂志

Objective:To compare the safety and efficacy of medial-lateral pinning (MLP) and lateral pinning (LP) in pediatric supracondylar humeral fractures.Methods:According to PRISMA procedure, the randomized controlled trial (RCT) of pediatric supracondylar humeral fractures in PubMed (Medline), EMBASE, the Cochrane Library databases (Cochrane Controlled Trials Register for RCTs) and Wanfang Data from 1 January, 1990 to 1 January, 2020 were retrieved. Two researchers independently extracted the data and evaluated the quality of the original studies; the random-effects model was used for analysis.Results:A total of 4 679 original literatures were retrieved and 11 literatures were finally included, involving 920 children. Meta analysis results showed that there were no statistical differences in excellent ratio of elbow joint function (Flynn criteria), incidence of iatrogenic nerve injury and incidence of pin tract/ superficial infection between MLP group and LP group: 74.3% (255/343) vs. 72.9% (250/343), 6.1% (16/262) vs. 1.6% (4/246) and 5.3% (14/264) vs. 7.6% (20/262); RR = 0.98, 0.43 and 1.31; 95% CI 0.90 to 1.07, 0.18 to 1.03 and 0.64 to 2.67, P>0.05; the incidence of reduction loss in MLP group was significantly lower than that in LP group: 16.6% (51/307) vs. 23.9% (72/301), and there was statistical difference ( RR = 1.39, 95% CI 1.02 to 1.89, P = 0.04). Conclusions:MLP fixation and LP fixation are equally efficacious for supracondylar humeral fractures in children. MLP fixation may reduce the risk of reduction loss without increasing the risk of iatrogenic nerve injury. Manual reduction and MLP percutaneous Kirschner wire fixation for the treatment of displaced supracondylar humeral fractures in children is recommended.

Pre-formulation physicochemical properties of component-based Chinese medicine of Qinqi Fengshi Fang / 中国中药杂志

Pre-formulation physicochemical properties of the component-based Chinese medicine of Qinqi Fengshi Fang were investigated to provide a research basis for the design of the dosage form for component-based Chinese medicine of Qinqi Fengshi Fang. The macroporous resin adsorption and refining technology was used to prepare the total glycosides extract of Gentianae Macrophyllae Radix, Panacis Majoris Rhizome and Corni Fructus respectively in the prescription of Qinqi Fengshi Fang. Their physicochemical properties were investigated, including solubility, wettability, hygroscopicity, equilibrium solubility, oil-water partition coefficient, and stability. The results showed that the total glycosides of Gentianae Macrophyllae Radix, Panacis Majoris Rhizome and Corni Fructus all had good solubility and wettability. The solubility index of each total glycoside component was greater than 85%, and the water absorption index was greater than 50%. In the range of pH 2.0-7.4, the equilibrium solubility of three kinds of total glycosides all increased with the increase of pH, showing a consistent change trend of solubility. The hydrophilicity was also suitable and similar. Overall, three kinds of total glycosides showed good stability, but strong hygroscopicity. The degree of hygroscopicity was as follows: total glycosides of Gen-tianae Macrophyllae Radix > total glycosides of Corni Fructus > total glycosides of Panacis Majoris Rhizome. Therefore, the hygroscopi-city needed to be considered in the preparation of the component-based Chinese medicine of Qinqi Fengshi Fang. The excipients and packaging materials can be properly selected to reduce the hygroscopicity of the preparation. This study provides a reference for the dosage form design of the component-based Chinese medicine of Qinqi Fengshi Fang.

Effect and mechanism of Huangkui capsuleon reduction of uremic toxin accumulation in an animal model of chronic kidney disease / 药学学报

Uremic toxins are harmful substances that accumulate in the body when the renal function declines in patients with chronic kidney disease (CKD). It is an important factor contributing to accelerated progression of CKD. There is no effective treatment for reducing uremic toxins. As an extensively used medicine for treatment of CKD in the clinic, Huangkui capsule is effective but the mechanism of its action remains unclear. This study investigated the effect of Huangkui on the accumulation of uremic toxins in CKD rats, with the discussion about its mechanism of action. UPLC-TQ/MS was used to detect the accumulation of uremic toxins in CKD rats after oral gavage with Huangkui. 16S rDNA sequencing technology was used to analyze the gut bacteria composition in rats. HPLC-FLD was used to detect the uremic toxins and their molecular precursors in feces. The effect and mechanism of Huangkui on the uremic toxin precursor in gut bacteria were studied by anaerobic culture system in vitro. All procedures were approved by the Institutional Animal Care and Use Committee of the Nanjing University of Chinese Medicine. The results showed that Huangkui (0.675 g·kg-1) could effectively inhibit the accumulation of uremic toxin indoxyl sulfate (IS) in CKD rats, with IS concentration in rat's plasma, liver and kidney decreased by 49.5%, 68.9% and 40.6%, respectively. Huangkui didn't affect the metabolic pathway of IS in host liver, didn't intervene the process of the IS precursor molecule indole conversion to IS. Instead, Huangkui significantly decreased the indole content in gut, with the indole in CKD rat's feces decreased by 46.4%, suggesting that the gut bacteria may be a target for intervene IS biosynthesis by Huangkui. Huangkui didn't affect the abundance of enterobacteriaceae bacteria (the main gut flora of indole synthesis) in CKD rats, suggesting that Huangkui didn't interfere with indole biosynthesis by directly affecting the abundance of indole synthesis related bacteria. Huangkui at 4 000, 400, 40, and 4 μg·mL-1 showed a dose-dependent inhibition of the indole production by gut bacteria in vitro. The bacteria tryptophan transport concentration decreased from 83.4 μmol·L-1 to 43.6 μmol·L-1 after co-incubated with Huangkui for 12 h, suggesting that Huangkui inhibited indole production of gut bacteria by interfering with tryptophan transportation. These results indicate that gut bacteria may be a potential target for alleviation of uremic toxin accumulation and for delaying CKD progression.

Detoxification mechanism of Jujubae Fructus and Crotonis Semen Pulveratum based on the toxicity of gastrointestinal system and diuretic effect in mice / 药学学报

The aim of this study was to investigate the effect of Jujubae Fructus (JF) on the gastrointestinal toxicity and diuretic effect of Crotonis Semen Pulveratum (CT). Forty-eight mice were randomly divided into the control group, low dose of CT group (0.039 g·kg-1·d-1, CTL), high dose of CT group (0.078 g·kg-1·d-1, CTH), JF group (9.75 g·kg-1·d-1), low dose of CT combined with JF group (CT 0.039 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTL), high dose of CT combined with JF group (CT 0.078 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTH). On the 9th day of oral administration, the urine output of all mice was measured. After oral administration for ten days, fresh fecal samples were collected, and the 16S rDNA sequencing method was used to study the changes of intestinal bacteria when CT used alone and combined with JF. All experimental protocols were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that JF slowed down the rapid diuretic effect of CT, and significantly increased serum interleukin-2 (IL-2), interleukin-6 (IL-6), gastrin (GAS), somatostatin (SS). JF also reduced small intestine injury and improved the disorder of intestinal flora caused by CT. Low dose CT combined with JF significantly decreased the relative abundance of Sphingomonas and Oscillospira. The level of Bilophila was decreased after the combined application of high dose CT and JF. The results suggest that JF exhibited a tendency to reduce the toxicity of CT in the aspects of serum immune index, intestinal movement, intestinal damage, and intestinal microflora structure. In addition, the JF could also slow down the rapid diuretic effect of CT, behaving a tendency to reduce the clinical effect of CT.

Incompatibility mechanism of Crotonis Semen Pulveratum and Glycyrrhizae Radix et Rhizoma based on diuretic effect and intestinal flora structure / 中国中药杂志

Based on the toxic characteristics caused by the compatibility between "Zaoji Suiyuan" and Glycyrrhizae Radix et Rhizoma, which was found in the previous studies, the expanded study was carried out on the incompatibility mechanism between Crotonis Semen Pulveratum(CT) and Glycyrrhizae Radix et Rhizoma(GU) with the diuretic effect and intestinal flora as the characteristic indexes. The results showed that GU could slow down the rapid diuretic effect of CT, which suggested a tendency of decreasing the efficacy. Both the high and low dose of CT could significantly induce the intestinal injury and change the intestinal bacteria structure of mice. Low dose CT combined with GU could significantly increase the levels of Streptococcus and Rikenellaceae＿ukn. The relative abundance of Desulfovibrio and Streptococcaceae＿ukn were increased after the combined application of high dose CT and GU. It also suggested that there was a risk of inflammation in the liver and intestines when combined application of these two herbs. The results revealed that the combination of CT and GU has a tendency to reduce the clinical effect and increase the toxicity from the aspects of its traditional efficacy and its effect on intestinal microflora structure, which could provide the data for the clinical use of CT.

Epidemiology and clinical features of scrub typhus in Hainan, China

Objective: To identify the epidemiology and clinical features of scrub typhus in Hainan Province, China. Methods: A total of 258 patients with acute febrile illness were recruited from four hospitals in Hainan between 1st June 2018 and 31th August 2019. Orientia tsutsugamushi-specific IgM/IgG and DNA were detected by goldimmuno- chromatographic assay and PCR on the patients' serum samples. The clinical and epidemiological characteristics of the laboratory-confirmed cases were recorded using a predesigned database. Results: The positive rates of IgM and IgG were 22.5% (58/258) and 39.9% (103/258), respectively, and the positive rate of PCR was 19.37% (50/258). There were 55 males and 48 females among the 103 IgG-positive patients. Patients of all age groups were affected (10 to 86 years); 65.0% of the adults aged 41 to 70 years (67/103); 64.1% of the patients were farmers (66/103). The patients resided in 12 counties and cities of Hainan, and the highest number of cases being reported among residents in Qiongzhong County and Haikou City (54/103, 52.4%). Seasonal variations in the incidence rate of scrub typhus was observed, with the peak incidence (53/103, 51.5%) occurring in the summer (June to August). The common presenting symptoms were fever (103/103, 100.0%), eschar or skin ulcer (38/103, 36.9%), and chills and rigors (30/103, 29.1%). The major complications were liver dysfunction (9/103, 8.7%). Four genotypes of Orientia tsutsugamushi were identified among these patients, including Karp, Kato, Gilliam and Ta763. The predominant genotype was Karp (33/51, 64.7%). Conclusions: Scrub typhus is endemic in Hainan, which predominantly affects residents with prolonged outdoor activities such as farming.

Elucidating the interaction of kansui and licorice by comparative plasma/tissue metabolomics and a heatmap with relative fold change / 药物分析学报

Although compatibility is highly advocated in traditional Chinese medicine (TCM), inappropriate com-bination of some herbs may reduce the therapeutic action and even produce toxic effects. Kansui and licorice, one of TCM"Eighteen Incompatible Medicaments", are the most representative cases of improper herbal combination, which may still be applied simultaneously under given conditions. However, the potential mechanism of their compatibility and incompatibility is unclear. In the present study, two different ratios of kansui and licorice, representing their compatibility and incompatibility respectively, were designed to elucidate their interaction by comparative plasma/tissue metabolomics and a heatmap with relative fold change. As a result, glycocholic acid, prostaglandin F2a, dihydroceramide and sphin-ganine were screened out as the principal alternative biomarkers of compatibility group; sphinganine, dihydroceramide, arachidonic acid, leukotriene B4, acetoacetic acid and linoleic acid were those of in-compatibility group. Based on the values of biomarkers in each tissue, the liver was identified as the compatible target organ, while the heart, liver, and kidney were the incompatible target organs. Furthermore, important pathways for compatibility and incompatibility were also constructed. These results help us to better understand and utilize the two herbs, and the study was the first to reveal some innate characters of herbs related to TCM"Eighteen Incompatible Medicaments".