Efficacy and Safety of Mulberry Twig Alkaloids Tablet for Treatment of Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study.

OBJECTIVE: To assess the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids, SZ-A) for treatment of type 2 diabetes in a randomized, double-blind, placebo-controlled multicenter clinical trial. METHODS: A total of 200 patients were randomized to receive SZ-A (n=100) or placebo (n=100) for 16 weeks. The data analysis system for electronic data capture clinical trial central randomization system was used for randomization and dispensing of drugs. The primary outcome was the change in glycosylated hemoglobin (HbA1c) level. The secondary outcome included the proportions of cases with HbA1c <7.0% and HbA1c <6.5%, fasting blood glucose (FBG), postprandial blood glucose (PBG), area under curve for the PBG (AUC0-2h), body weight, and body mass index (BMI). Adverse events (AEs), severe adverse events (SAEs), treatment-related adverse events (TAEs), gastrointestinal disorders (GDs), blood pressure, routine blood tests, and liver and kidney function were monitored. RESULTS: Compared with baseline, the change of HbA1c at week 16 was -0.80% (95% CI: -0.98% to -0.62%) and -0.09% (95% CI: -0.27% to 0.09%) in SZ-A group and placebo group, respectively. The proportion of patients with HbA1c <7% and <6.5% was higher in the SZ-A group than in the placebo group (46.8% vs. 21.6% and 29.9% vs. 10.8%). The observed values and changes in FBG, 1 h-PBG, 2 h-PBG, and AUC0-2h differed significantly between groups (P<0.001), but differences were not significant in body weight and BMI (P>0.05). The incidence rates of AEs, TAEs, and GDs differed significantly between groups (P=0.010, P=0.005, and P=0.006, respectively), whereas the incidence rates of SAEs showed no significant differences between groups (P=1.000). CONCLUSION: SZ-A are effective and safe for treatment of type 2 diabetes. The protocol was registered in http://www.chictr.org.cn/showproj.aspx?proj=60117 (ChiCTR2000038550).

[Clinical effect of cortical incision with rapid maxillary expansion to assist orthodontic-orthognathic treatment of skeletal Class â ¢ malocclusion].

PURPOSE: To investigate the clinical effect of rapid maxillary expansion with cortical osteotomy combined with orthodontic- orthognathic treatment for skeletal Class Ⅲ malocclusion. METHODS: A total of 84 patients with skeletal Class Ⅲ malocclusion admitted to Jining Dental Hospital from March 2018 to May 2020 were randomly divided into experimental group and control group, with 42 cases in each group. The control group was treated with orthodontic-orthognathic treatment, while the experimental group was treated with orthodontic-orthognathic treatment with rapid maxillary arch expansion by cortical incision. The time of closing gap, alignment time, maxillary first molar and maxillary central incisor tooth movement distance in the sagittal direction were compared between the two groups. Before treatment and 4 weeks after treatment, the vertical distance from the end of the upper central incisor edge to the horizontal plane(U1I-HP), the distance from the apex of the upper central incisor to the coronal plane(U1I-CP), the vertical distance from the edge of the upper pressure groove to the coronal plane(Sd-CP), the vertical distance from the upper alveolar seat point to the horizontal plane(A-HP), the vertical distance from the point of the upper lip to the coronal plane(Ls-CP), and the vertical distance from the inferior point of nose to coronal plane(Sn-CP) were measured, and the relevant changes were calculated. During the treatment period, the complications of the two groups were compared. SPSS 20.0 software package was used for statistical analysis of the data. RESULTS: There was no significant difference in alignment time, A-HP change, Sn-CP change, maxillary first molar movement distance and maxillary central incisor movement distance between the two groups (P＞0.05). The closing interval in the experimental group was significantly shorter than that of the control group (P＜0.05). The changes of U1I-HP, U1I-CP, Sd-CP, and Ls-CP in the experimental group were significantly higher than those in the control group (P＜0.05). There was no significant difference in the incidence of complications between the two groups during treatment (P＞0.05). CONCLUSIONS: Rapid maxillary expansion of cortical incision assisted orthodontic-orthognathic treatment of skeletal Class Ⅲ malocclusion patients can shorten the closing gap time and improve the treatment effect, which has no obvious influence on the sagittal direction of the teeth.

[Expert consensus statement on treatment of type 2 diabetes with Xiaoke Pills in clinical practice].

Xiaoke Pills are Chinese and Western medicine compound preparations with effects of nourishing kidney and Yin,and supplementing Qi and promoting fluid. It is widely used in clinical treatment of type 2 diabetes( Qi and Yin deficiency syndrome),and continuously included in 2010,2013 and 2017 editions of Chinese prevention guide for type 2 diabetes. For the purpose of accurate positioning and rational use in clinic,it is necessary to further define the curative effect,indications,medication precautions and contraindications of Xiaoke Pills,in order to improve medication safety. This consensus was reached by reference of international clinical guidelines and expert consensus approach based on clinical evidence-based evidence,expert experience and standard specification. The evidence-based evaluation was oriented to clinical problems summarized by no less than 200 front-line clinical physicians in two rounds.GRADE system was adopted for quality classification and evaluation of the evidences,and then the nominal group method was used to form consensus recommendations or suggestions. This consensus defined the curative effect advantages,target users,dosage,administration method,contraindications and precautions of Xiaoke Pills,and provided valuable reference for the clinical use of the drug. Thisconsensus still needs to be updated and revised based on new clinical problems and evidence-based evidence in practical application in the future.

Recent Development of Coumarin Derivatives as Potential Antiplasmodial and Antimalarial Agents.

Malaria still remains one of the leading deadliest diseases throughout the world, leading to around 1 million deaths annually. The emergence and spread of growing resistance to the firstline antimalarials are an alarming the serious problem in malaria control, demanding the need for new drugs more potent than earlier with improved Absorption, Distribution, Metabolism, and Excretion (ADME) profiles. Coumarins, which exhibited various biological properties, also displayed potential in vitro antiplasmodial and in vivo antimalarial activities. Moreover, many of coumarin derivatives have already been used in clinical practice for the treatment of several diseases. Therefore, coumarin derivatives play a pivotal role in medicinal chemistry, also making them promising candidates for the treatment of malaria. This review aims to summarize the recent advances made towards the development of coumarin-containing derivatives as antiplasmodial and antimalarial agents and their structure-activity relationship is also discussed.

Recent Developments of Coumarin Hybrids as Anti-fungal Agents.

Fungi place a huge burden on global healthcare systems attributed to the fact that fungal infections are responsible for the high morbidity and mortality rates in patients who received stem cell transplantation, antineoplastic chemotherapy, organ transplants or suffered Human Immunodeficiency Virus (HIV) infection. Unfortunately, almost none of the representative anti-fungal agents currently used in clinical therapy are ideal in terms of efficacy, anti-fungal spectrum or safety. Moreover, the rapid development of resistance to existing anti-fungal drugs has further aggravated the mortality and spread of fungi, creating an urgent need for novel anti-fungal agents. The broad spectrum of biological activities and successful usage in clinic made coumarins a promising anti-fungal candidate. Furthermore, hybridization of other pharmacophores with coumarin motif may enhance the anti-fungal efficacy, broaden the anti-fungal spectrum and improve the safety profiles. Thus, numerous coumarin hybrids have been assessed for their anti-fungal activities, and some of them showed promising potency and may have a novel mechanism of action. This review aims to outline the recent development of coumarin hybrids as potential anti-fungal agents and summarize their Structure-Activity Relationship (SAR) to provide an insight for rational designs of more active agents.

[Retrospective study on Chinese medicine syndrome patterns and their associated factors in patients with type 2 diabetic nephropathy stage III].

OBJECTIVE: To explore the relationship between Chinese medicine syndrome patterns (CMSP) and their associated factors in patients with type 2 diabetic nephropathy stage III (DN2-3). METHODS: Retrospective analysis was conducted on 209 patients with type 2 diabetes mellitus (T2DM). The patients were allocated into two groups, the DN2-3 group and the control group. Some related clinical materials and laboratory indexes, including age, course of disease, body mass index (BMI), glycosylated hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), blood levels of total cholesterol (TC), triglyceride (TG), high and low density lipoprotein (HDL and LDL), serum creatinine (Scr) and microalbuminuria (MALB) as well as their CMSP (both the essential syndrome and the superficial syndrome) in the DN2-3 group were collected and compared. RESULTS: Significant differences were found between the DN2-3 group and the control group in aspects of course of disease (months, 107.74 +/- 96.19 vs. 82.03 +/- 79.10), BMI (kg/m2, 26.25 +/- 4.02 vs. 24.95 +/- 3.56) and Scr level (mmoL/L, 71.93 +/- 24.24 vs. 65.91 +/- 13.70, P < 0.05). The qi-yin deficiency SP (38 cases, 36.19%), and the blood stasis (51 cases, 48.58%) presented as the dominant essential and superficial CM-SP respectively in DN2-3 patients, holding the highest proportion. Analysis on the relationship of associated indices among patients with different CMSP showed statistical differences presented in level of MALB, i.e. which in pi-shen qi-deficiency SP (128.77 +/- 103.59 mg/24 h) was higher than in yin-deficiency dryness-fire SP and qi-yin deficiency SP (88.43 +/- 68.93 mg/24h and 82.60 +/- 55.22 mg/24 h, P < 0.05); it also presented in HbA1c (%) and TG levels(mmol/L), those in stasis SP were 10.73 +/- 2.71 and 2.29 +/- 1.58 ), in dampness SP were 8.80 +/- 2.19% and 4.37 +/- 5.92, and in stasis-phlegm SP were 8.83 +/- 2.09 and 2.40 +/- 2.18 (all P < 0.05). CONCLUSIONS: The risk factors for occurrence of DN2-3 may be the course of disease, BMI and Scr. Qi-yin deficiency with blood-stasis is the most commonly encountered syndrome in patients with DN2-3. Relations of MALB with Pi-Shen qi-deficiency pattern; HbA1c with blood-stasis pattern, and TG with dampness syndrome are distinctly exhibited in them.

[Analysis of the secondary effluent of municipal wastewater in north China].

The secondary effluent from a municipal sewage treatment plant was fractionated into three parts: the dissolved, the near-colloidal and the suspended. The variation of each composition was investigated individually during winter, spring and summer. The fractionation study revealed that the dissolved COD and DOC accounted for 78.2%-86.5% of total COD and 82.6%-86.6% of TOC, respectively. The molecular weight distribution (MWD) of the secondary effluent indicated that the organics with molecular weight (MW) < 1000 accounted for 56.3%-62.8% of total organics. The organic components constituted 75.54%-89.93 % of the mixture of suspended and near-colloidal matter. The size distribution of the particles showed that the particles ranging from 2.00 to 6.84 microm constituted more than 80% of the total particles. The secondary effluent was relatively poor biodegradable with only 0.195-0.283 of BOD5/COD ratio and 0.156-0.26 of BDOC/DOC ratio. The GC/MS analysis detected 43 and 26 kinds of compounds in dissolved and in suspended forms, respectively, and most of them are bio-refractory according to the functional groups of the chemicals. Biodegradability of the secondary effluent should be enhanced for improving the sequential biochemical removal efficiency for the organic matter.