ObjectiveTo investigate the mechanisms by which the combination of berberine （BBR） and baicalin （BAI） ameliorates type 2 diabetes mellitus （T2DM） due to internal accumulation of dampness-heat from the perspectives of gut microbiota and metabolomics. MethodsAntibiotics were used to induce pseudo-sterile mice. Thirty pseudo-sterile mice were randomized into a normal fecal microbiota transplantation group （n=10） and a T2DM （syndrome of internal accumulation of dampness-heat） fecal microbiota transplantation group （n=20）. The mice were then administrated with suspensions of fecal microbiota from healthy volunteers and a patient with T2DM due to internal accumulation of dampness-heat by gavage， respectively. Each mouse received 200 µL suspension every other day for a total of 15 times to reshape the gut microbiota. The T2DM model mice were then assigned into a model group （n=8） and a BBR-BAI group （n=11）. BBR was administrated at a dose of 200 mg·kg^-1， and BAI was administrated in a ratio of BBR-BAI 10∶1 based on preliminary research findings. The administration lasted for 8 consecutive weeks. Fasting blood glucose （FBG）， glycated hemoglobin （HbA1c）， insulin （INS）， triglycerides （TG）， total cholesterol （CHOL）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） levels were measured to evaluate the effects of the BBR-BAI combination on glucose and lipid metabolism and liver function in T2DM mice. Hematoxylin-eosin staining was employed to observe pathological changes in the colon tissue. The expression of claudin-1， zonula occludens-1 （ZO-1）， and occludin in the colon tissue was determined by Western blot. Real-time quantitative polymerase chain reaction（Real-time PCR） was employed to assess the levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） in the colon tissue. The fecal microbiota composition and differential metabolites were analyzed by 16S rRNA sequencing and ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry （UPLC-Q-TOF-MS）， respectively. ResultsThe BBR-BAI combination lowered the FBG， HbA1c， and INS levels （P<0.05， P<0.01） and alleviated insulin resistance （P<0.01） in T2DM mice. Additionally， BBR-BAI elevated the levels of ZO-1， occludin， and claudin-1 （P<0.05， P<0.01） and down-regulated the expression levels of TNF-α， IL-1β， and IL-6 in the colon （P<0.05， P<0.01）. The results of 16S rRNA sequencing showed that BBR-BAI increased the relative abundance of Ligilactobacillus， Phascolarctobacterium， and Akkermansia （P<0.05）， while significantly decreasing the relative abundance of Alistipes， Odoribacter， and Colidextribacter （P<0.05）. UPLC-Q-TOF-MS identified 28 differential metabolites， which were primarily involved in arachidonic acid metabolism and α-linolenic acid metabolism. ConclusionBBR-BAI can ameliorate T2DM due to internal accumulation of dampness-heat by modulating the relative abundance of various bacterial genera in the gut microbiota and the expression of fecal metabolites.

Gegen Qinliantang is a representative prescription for dual releasing of exterior and interior and treating diarrhea with fever in the Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）. This prescription consists of Puerariae Lobatae Radix， Scutellariae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. The combination of the four herbal medicines has the ability to clear both the exterior and the interior， thereby halting diarrhea and clearing heat. According to the idea of treating different diseases with the same method， Gegen Qinliantang is used in clinical practice to treat type 2 diabetes mellitus （T2DM）， which demonstrates positive outcomes. T2DM is a chronic metabolic disease characterized by elevated blood glucose levels. The etiology and pathogenesis of T2DM are complex， mainly related to heredity， lifestyle， environment， diet and other factors. Clinical observations and experimental studies have shown that Gegen Qinliantang and its effective ingredients have significant effects of preventing and treating T2DM. Clinically， Gegen Qinliantang is often applied with modification， or in combination with Western drugs， demonstrating better therapeutic effects than Western drugs alone. Clinical practice has confirmed that Gegen Qinliantang can effectively alleviate the clinical symptoms， reduce the occurrence of complications， and alleviate gastrointestinal adverse reactions in T2DM patients. Experimental studies have demonstrated that Gegen Qinliantang can ameliorate insulin resistance and boost pancreatic function by regulating the insulin and inflammation signaling pathways， alleviating oxidative stress， and modulating gut microbiota to treat T2DM. Nevertheless， more thorough studies remain to be carried out to decipher the mechanism of Gegen Qinliantang in ameliorating insulin resistance in T2DM. To provide theoretical and data references for the subsequent in-depth research on the mechanism of Gegen Qinliantang in treating T2DM and the prevention and treatment of this disease， this article systematically reviews the clinical and experimental research progress of Gegen Qinliantang in ameliorating insulin resistance in T2DM.

The outbreak and spread of coronavirus disease 2019 (COVID-19) highlighted the importance and urgency of the research and development of therapeutic drugs. Very early into the COVID-19 pandemic, China has begun developing drugs, with some notable progress. Herein, we summarizes the anti-COVID-19 drugs and promising drug candidates originally developed and researched in China. Furthermore, we discussed the developmental prospects, mechanisms of action, and advantages and disadvantages of the anti-COVID-19 drugs in development, with the aim to contribute to the rational use of drugs in COVID-19 treatment and more effective development of new drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the variants. Neutralizing antibody is an effective approach to overcome COVID-19. However, drug resistance induced by rapid virus mutation will likely to challenge neutralizing antibodies. Taking into account current epidemic trends, small molecule drugs have a crucial role in fighting COVID-19 due to their significant advantage of convenient administration and affordable and broad-spectrum. Traditional Chinese medicines, including natural products and traditional Chinese medicine prescriptions, contribute to the treatment of COVID-19 due to their unique mechanism of action. Currently, the research and development of Chinese anti-COVID-19 drugs have led to some promising achievements, thus prompting us to expect even more rapidly available solutions.

Objective: This study aims to investigate the epidemiological distribution of HFMD and quantify the association of temperature with the incidence of children’s HFMD in Nanjing, China. Methods: Daily counts of HFMD in children under 5 years and daily meteorological variables during 2011-2016 were obtained. Descriptive statistics were used to describe the epidemiological characteristics and distributed lag non linear model (DLNM) was used to assess the associations of temperature on HFMD cases. Results: A total of 104 977 HFMD cases aged 0-5 years were reported in Nanjing during the study period and the male to female sex ratio was 1.49∶1. The average annual incidence was 213.5 per 100 000. A bimodal seasonal pattern was observed and the south and west were found to be the high incidence areas in the city. Of these laboratory confirmed enteroviruses positive cases, 32.5% cases were positive for EV-A71 infections, 29.1% cases were positive for CV-A16 infections and 38.4% cases were positive of other enteroviruses infections. The temperature HFMD relationships were non linear and showed obvious lag effects. The cumulative relative risk presented as an approximately inverted U shape over 14 days and peaked at 25.7 ℃ with value of 2.71(95%CI=1.93-3.81). Subgroup analyses revealed that males and children aged <1 year were more vulnerable to temperature variations. Conclusion Epidemiological characteristics of HFMD among children aged 0-5 years old in Nanjing presented temporal and regional distribution. The temperature has significant impact on children’s HFMD occurrence.

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To under-stand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot,real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phospho-proteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloro-plasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of pho-tosystem (PS) Ⅱ, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.

Objective:To investigate the clinical effect of enteral nutrition (EN) on patients with acute exacerbation of chronic obstructive pulmonary disease (COPD).Methods:96 cases of acute exacerbation of COPD patients admitted to our hospital from January 2015 to December 2016 were randomly divided into observation group (48 cases) and control group (normal diet,48 cases).The patients in two groups were given anti-infection and other symptomatic treatments equally.The serum protein levels and pulmonary function in the two groups were compared after 2 weeks.Furthermore,antibiotic use durations,hospitalization days and the re-admission rates within 3 months were observed and compared between two groups.Results:The serum albumin and pre-albumin levels,FEV1 and FEV1/FVC in the observation group were significantly elevated in comparison with those in the control group.And the antibiotic use durations,hospitalization days and the re-admission rates within 3 months remarkably decreased in the observation group (P ＜ 0.05).Conclusion:Enteral nutrition could improve the nutritional status and pulmonary function in patients with acute exacerbation of COPD,shortening the length of hospital stay and the durations of antibiotic use and reducing the rates of re-admission.Enteral nutrition may be worth applying widely in clinical COPD patients in future.

Background:Diagnosis of liver cirrhosis in early stage with early intervention may stabilize disease progression, avoiding or delaying the occurrence of decompensation. Seeking non-invasive serum biomarkers is becoming an important topic in the diagnosis and assessment of liver cirrhosis. Aims:To study the value of serum miR-192 and miR-29a as non-invasive biomarkers for the diagnosis of liver cirrhosis. Methods:Differentially expressed serum miRNAs between patients with liver cirrhosis and healthy controls were screened through online literature retrieval and then confirmed by real-time PCR. Serum levels of two confirmed miRNAs,miR-192 and miR-29a were analyzed in 120 patients with liver cirrhosis and 76 healthy volunteers by real-time PCR. A mathematical model of combined detection of miR-192 and miR-29a for diagnosis of liver cirrhosis was established by binary logistic regression. The diagnostic performance of various non-invasive serum indicators was evaluated by ROC curve analysis. Results:Compared with healthy controls,expression level of serum miR-192 in cirrhotic patients was significantly increased and that of serum miR-29a was significantly reduced(P ﹤ 0. 001). The diagnostic performance of risk score obtained from mathematical model of combined detection of serum miR-192 and miR-29a was superior to that of single miRNA detection or other non-invasive serum indicators,such as APRI,FIB-4 and ARR,the areas under ROC curve of the above mentioned indicators were 0. 968,0. 887,0. 933,0. 796,0. 793,and 0. 571,respectively. Serum levels of miR-192,miR-29a and the risk score of their combined detection were significantly correlated with the stage of liver cirrhosis according to the Child-Pugh classification( P ﹤ 0. 05). Conclusions:Serum miR-192,miR-29a and the risk score of their combined detection might be novel non-invasive biomarkers for the diagnosis and assessment of liver cirrhosis.

Objective To analysis the modified Gleason scoring system for predicting the prognosis after radical prostatectomy.Methods A total of 242 patients who received radical prostatectomy from April,2006 to October 2011 were recruited.The patients who lost follow-up or had adjuvant radiation or hormonal therapy or had visceral or bone metastasis were excluded,the remaining 168 patients were evaluated in the present study.The patients' age ranged from 53 to 85 years old (mean age 69 years old).The mean PSA level was 13.31ng/ml (ranging from 4.59 to 36.12 ng/ml).According to the traditional Gleason scoring system,there were 50 patients in Gleason ≤ 6 group,86 patients in Gleason 7 group and 32 patients in Gleason≥8 group.Patients were divided in five groups according to the modified Gleason scoring system.There were 50 patients in Gleason ≤6 group,67 in Gleason 3 + 4 group,19 in Gleason 4 + 3 group,15 in Gleason 8 group and 17 in Gleason 9-10 group.The biochemical-free-survival curve was drawn by Kaplan-Meier method and the multivariate Cox regression models were used to evaluate the clinical and pathological variables for the development of biochemical recurrence.ROC curve analysis was used to determine the predicted value for 5-year BCR of modified and traditional Gleason scoring.Results Significant differences were noted between the modified Gleason scoring groups and traditional Gleason scoring groups in PSA value (P =0.005),pathological stage (P =0.002),extraprostatic extension (P =0.003),seminal vesicle invasion (P =0.004),lymph node involvement (P =0.049) and positive surgical margin (P =0.006).With a median follow-up of 68 months(ranging from 7 to 98 months),5-year BFS rates for men with Gleason grade ≤6,3 + 4,4 + 3,8 and 9-10 tumours on RP pathology were 84.0％ (42/50),76.1％ (51/67),57.9％(11/19),40.0％ (9/15),29.4％ (5/17),respectively.On multivariate analysis,the HR value of Gleason 3 + 4 group and Gleason 4 + 3 group were 1.736 and 2.075 (P ＜ 0.05).The area under the curve in modified and traditional Gleason scoring were 0.698 (95％ CI 0.609-0.788) and 0.674 (95％ CI O.584-0.764),respectively.Conclusions The modified Gleason scoring system is related to the prostate cancer grade and its survival rate.Therefore,it can predict prognosis accurately in patients with prostate cancer.It can potential to reduce overtreatment in patients with Gleason 3 +4 prostate cancer.

Resting energy expenditure is the main indicator to assess energy consu mpit on of ap tine ts. The ne eryg expenditure of critically ill children can be influenced by many factors.Different ts atse of diseases are followed by different values of resting energy expenditure.Right now,indirect calorimetry is the “golden standard” of measurement of energy metabolism.Indirect calorimetry can be used to accurately grasp energy expenditure of patients.And it is beneficial to optimization of nutrition support,also for individualized nutri-tion therapy.

Objective Research has indicated that hydrogen sulfide(H2S) can regulate the function of N-methyl-D-aspartate re-ceptors(NMDARs) in the brain, but its effect on brain resuscitation requires further investigation.The study was to speculate the effect of H2 S on brain resuscitation as well as the underlying mechanism of neuroresuscitation by investigating the effects of hydrogen sulfide and hypo-thermia on the expression of NR2A, NR2B and phospho-cAMP response element binding protein (p-CREB) of NMDARs in the hippocampus after global cerebral ischemia following by reperfusion. Methods 100 male SD rats were randomly divided into five groups(n=20):sham operation group, model group, mild hypothermia group, NaHS group, NaHS combined mild hypothermia group.Pulsinelli-Brierley four-ves-sel occlusion method was induced to build the injury rat model by reperfusion after global cerebral ischemia .After 15 minutes'ischemia, im-mediate injection of 14μmol/kg NaHS was performed intraperitoneally on NaHS group and NaHS combined mild hypothermia group , while skin cooling(rectal temperature=32-33℃) was done on mild hypothermia group and NaHS combined mild hypothermia group .6 hours late,r hip-pocampus were extracted from rat heads.Respectively, spectrophotometer was applied to measure the content of H2S, Western blot for the expres-sions of NR2 A,NR2 B and pC-REB, and RTP-CR for mRNA level of brain derived neurotrophic (BDNF). HE staining was also performed on brain tissues 72hours after reperfusion on 4 rats from each group to evaluate the pathological changes of pyramidal neurons in CA1 region. R esul ts The content of H 2 S increased in each of the four groups after ischemia-reperfusion compared with sham operation group ( 15.2 ±2.0 nmol/g) (P<0.05).In comparison to model group (25.2 ±3.5 nmol/g), NaHS group (37.5 ±4.0 nmol/g) and NaHS combined mild hypothermia group (38.7 ±4.4nmol/g ) resulted in significant high content of H2S(P<0.05), while mild hypothermia group(26.5 ±3.5nmol/g ) got a mild increase(P>0.05).The gray values of NR2A and NR2B in each group increased compared with sham operation group(P<0.05), re-sulting in NR2A/NR2B<1 in model group and mild hypothermia group while NR2A/NR2B>1 in NaHS group and NaHS combined mild hy-pothermia group.Compared with the expression of p-CREB(0.55 ±0.06) in model group, there were significant increases in mild hypother-mia group(0.99 ±0.15), NaHS group(1.05 ±0.12), NaHS combined mild hypothermia group(1.02 ±0.15)(P<0.05).Compared with the expression of BNDF mRNA(0.83 ±0.12) in model group, there were significant increases in mild hypothermia group (1.11 ±0.13), NaHS group(1.27 ±0.16), NaHS combined mild hypothermia group(1.35 ±0.16)(P<0.05).In comparison to model group, there were signifi-cant alleviation in the injury of pyramidal neurons in hippocampal CA1 region in mild hypothermia group, NaHS group, NaHS combined mild hypothermia group, with the best effect in NaHS combined mild hypothermia group . Conclusion Hydrogen sulfide combined mild hypo-thermia can selectively activate synaptic NMDA receptors and trigger the prosurvival CREB signaling pathway to exert brain resuscitation .