ObjectiveTo investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress （CUMS）， and to examine its influence on the c-Jun N-terminal kinase （JNK）/proto-oncogene protein （c-Myc）/tumor suppressor protein 53 （p53） signaling pathway， thereby revealing its potential functional mechanism. MethodsA total of 72 male SD rats were randomly divided into six groups using a strict random number table： blank group， model group， fluoxetine group （3.6 mg·kg^-1）， and high-， medium-， and low-dose Suanzaoren Tang groups （10， 5， 2.5 g·kg^-1），with 12 rats in each group. A depression model was established using isolation combined with CUMS. Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days. Behavioral indicators such as sucrose water consumption and open field test scores were recorded. Western blot and immunohistochemistry （IHC） were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway， and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to evaluate the number of apoptotic cells in the hippocampus. ResultsCompared with the blank group， the model group exhibited a significantly reduced sucrose preference index （P<0.01）， a lower total score of horizontal and vertical movements in the open field test （P<0.01）， significantly increased expression of JNK， c-Myc， and p53 proteins in the hippocampus （P<0.01）， and a higher number of TUNEL-positive cells in the hippocampus （P<0.01）. Compared with the model group， the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high- and medium-dose Suanzaoren Tang groups and the fluoxetine group （P<0.05， P<0.01）. The expression of JNK， c-Myc， and p53 proteins significantly decreased in all Suanzaoren Tang groups （high， medium， and low doses） and the fluoxetine group （P<0.05， P<0.01）. The number of TUNEL-positive cells in the hippocampus also significantly decreased in these groups （P<0.01）. ConclusionSuanzaoren Tang can regulate the expression of JNK/c-Myc/p53 proteins in the hippocampus of depression model rats， and its antidepressant mechanism may be related to its protective effect on hippocampal neurons.

With the aging of the global population， osteoporosis （OP） is becoming a major public health concern worldwide. Currently， the commonly used anti-osteoporosis drugs in clinical practice have limited application due to many side effects. Therefore， developing more effective and safer strategies for the prevention and treatment of OP has become a research focus in this field. In recent years， the clinical efficacy and advantages of traditional Chinese medicine （TCM） in treating OP have been gradually recognized. With the deepening pharmacological research on TCM for OP prevention and treatment， it is found that the active ingredients of Scutellaria baicalensis can promote bone formation or inhibit bone resorption by regulating signaling pathways， including Wnt/β-catenin， osteoprotegerin （OB）/receptor activator of nuclear factor-κB ligand （RANKL）/RANK （OPG/RANKL/RANK）， and bone morphogenetic protein 2 （BMP-2）/Smad， mitogen-activated protein kinase （MAPK）， and mammalian target of rapamycin （mTOR）. However， existing research on active ingredients of S. baicalensis for OP treatment is scattered， making it difficult for scholars to gain a systematic understanding of its research and application. This review summarized the literature on the active ingredients of S. baicalensis in OP treatment worldwide， clarified their mechanisms of action， and explored some issues， providing references for the integration of TCM in OP prevention and treatment.

With the aging of the global population， osteoporosis （OP） is becoming a major public health concern worldwide. Currently， the commonly used anti-osteoporosis drugs in clinical practice have limited application due to many side effects. Therefore， developing more effective and safer strategies for the prevention and treatment of OP has become a research focus in this field. In recent years， the clinical efficacy and advantages of traditional Chinese medicine （TCM） in treating OP have been gradually recognized. With the deepening pharmacological research on TCM for OP prevention and treatment， it is found that the active ingredients of Scutellaria baicalensis can promote bone formation or inhibit bone resorption by regulating signaling pathways， including Wnt/β-catenin， osteoprotegerin （OB）/receptor activator of nuclear factor-κB ligand （RANKL）/RANK （OPG/RANKL/RANK）， and bone morphogenetic protein 2 （BMP-2）/Smad， mitogen-activated protein kinase （MAPK）， and mammalian target of rapamycin （mTOR）. However， existing research on active ingredients of S. baicalensis for OP treatment is scattered， making it difficult for scholars to gain a systematic understanding of its research and application. This review summarized the literature on the active ingredients of S. baicalensis in OP treatment worldwide， clarified their mechanisms of action， and explored some issues， providing references for the integration of TCM in OP prevention and treatment.

Objective To explore the comparative study of constructing prediction models for muscle invasive of bladder cancer based on different machine learning algorithms combined with MRI radiomic.Methods A total of 187 bladder cancer patients who underwent MRI examination and were confirmed by pathology were retrospectively selected.Patients were randomly divided into a training set and a test set in a 7∶3 ratio.The patients were divided into muscle invasive bladder cancer(MIBC)group and non-muscle invasive bladder cancer(NMIBC)group according to the surgical pathology results.Tumor volume of interest(VOI)was outlined on the images of T2 WI,diffusion weighted imaging(DWI),and apparent diffusion coefficient(ADC),and the radiomic features were extracted by A.K software,and dimensionality reduction was performed using the maximum relevance minimum redundancy(mRMR)algorithm combined with least absolute shrinkage and selection operator(LASSO).Six machine learning algorithms,including K-nearest neighbor(KNN),decision tree(DT),support vector machine(SVM),logistic regression(LR),random forest(RF),and explainable boosting machine(EBM)were used to construct the radiomic model and calculate the corresponding area under the curve(AUC),accuracy,sensitivity,and specificity,respectively.Results Six machine learning algorithms,including KNN,DT,SVM,LR,RF,and EBM were used to construct the radiomic model,and the AUC values for predicting MIBC in the training set were 0.863,0.838,0.853,0.866,0.977,0.997,and in the test set were 0.748,0.833,0.860,0.868,0.870,0.900.Among them,the MRI radiomic model constructed based on EBM had the highest predictive efficacy for MIBC,with AUC values,accuracy,sensitivity and specificity of 0.997,0.977,0.957 and 0.981 in the training set,and 0.900,0.877,0.800,and 0.894 in the test set,respectively.Conclusion Multiple machine learning algorithms combined with MRI radiomic to construct models have good predictive efficacy for MIBC,and the model constructed based on EBM shows the highest predictive value.

Phosphatidylinositol-3-kinase (PI3K) inhibitors can increase the sensitivity of tumor cells to Poly ADP-ribose polymerase-1 (PARP-1) inhibitors. Therefore, the simultaneous inhibition of the PARP-1 and PI3K activities are expected to overcome the drug resistance of PARP-1 inhibitors.In our previous work, two compounds XW-1 and WZ-1 with excellent activities against PARP-1 and PI3K were obtained with the limitation to further study due to their poor water solubility.Therefore, XW-1 and WZ-1 were chosen as lead compounds to optimize their solubility by introducing a salt-forming site via a urea group, and 11 novel compounds were designed and synthesized. The structure of all target compounds was confirmed by 1H NMR, 13C NMR, and HRMS.The enzyme activities of the compounds against PARP-1 and PI3K were measured, and the results showed that most of the compounds demonstrated good inhibitory activities against PARP-1 and PI3K.Based on the above result, the inhibitory activities of compounds 8b, 8e, and 8f against MDA-MB-231, MDA-MB-468, HCC1937, HCT116, and olaparib-resistant HCT116R were determined by MTT, respectively.Additionally, the structure-activity relationship was discussed. The results showed that these compounds displayed excellent antiproliferation activity.Among them, compound 8f demonstrated antiproliferation remarkably against all five tumor cells, which was more potent than that of olaparib, and was comparable to that of BKM120.Furthermore, the solubility of hydrochloride salts of compound 8b and 8f was significantly improved compared to the lead compounds.The results of this study will provide a theoretical basis for the further development of PARP-1 and PI3K dual-target inhibitors with good pharmaceutical properties and strong inhibitory activities.

Abernethy malformation， also known as congenital portosystemic shunts， is rare in clinical practice， with less than 300 cases reported in the global literature up to 2019. The disease can have serious complications such as pulmonary hypertension， liver tumor， and liver failure and tends to have an extremely poor prognosis， and early diagnosis and active and effective treatment can reduce and delay the onset of complications. In this case， portography combined with balloon occlusion helped to display the underdeveloped slender portal vein with dysplasia， so that the child who was formerly misdiagnosed with type Ⅰ Abernethy malformation was diagnosed with type Ⅱ Abernethy malformation， and then the child was successfully treated by transcatheter closure. This article gives a detailed report of this case.

Adolescent ; Adult ; Age Distribution ; Aged ; Basic Reproduction Number ; COVID-19/virology* ; China/epidemiology* ; Disease Outbreaks ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Sex Ratio ; Young Adult

Objective The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number ( R 0 ) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention. Method The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R 0 . Result Among the four methods, the EG method fitted the data best. The estimated R 0 was 3.49 (95% CI : 3.42-3.58) by using EG method. The R 0 was estimated to be 2.95 (95% CI : 2.86-3.03) after taking control measures. Conclusion In the early stage of the epidemic, it is appropriate to estimate R 0 using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.

Objectives: Fitting and forecasting the trend of COVID-19 epidemics. Methods: Based on SEIR dynamic model, considering the COVID-19 transmission mechanism, infection spectrum and prevention and control procedures, we developed SEIR^{+ CAQ} dynamic model to fit the frequencies of laboratory confirmed cases obtained from the government official websites. The data from January 20, 2020 to February 7, 2020 were used to fit the model, while the left data between February 8-12 were used to evaluate the quality of forecasting. Results: According to the cumulative number of confirmed cases between January 29 to February 7, the fitting bias of SEIR^{+ CAQ} model for overall China (except for cases of Hubei province), Hubei province (except for cases of Wuhan city) and Wuhan city was less than 5%. For the data of subsequent 5 days between February 8 to 12, which were not included in the model fitting, the prediction biases were less than 10%. Regardless of the cases diagnosed by clinical examines, the numbers of daily emerging cases of China (Hubei province not included), Hubei Province (Wuhan city not included) and Wuhan city reached the peak in the early February. Under the current strength of prevention and control, the total number of laboratory- confirmed cases in overall China will reach 80 417 till February 29, 2020, respectively. Conclusions The proposed SEIR^{+ CAQ} dynamic model fits and forecasts the trend of novel coronavirus pneumonia well and provides evidence for decision making.

Objectives:The COVID-19 has been the public health issues of global concern, but the incubation period was still under discussion. This study aimed to estimate the incubation period distribution of COVID-19.Methods:The exposure and onset information of COVID-19 cases were collected from the official information platform of provincial or municipal health commissions. The distribution of COVID-19 incubation period was estimated based on the Log- normal, Gamma and Weibull distribution by interval-censored data estimation method.Results:A total of 109 confirmed cases were collected, with an average age of 39.825 years. The median COVID-19 incubation period based on Log-normal, Gamma, and Weibull distribution were 4.958 ( P25- P75: 3.472-7.318) days, 5.083 ( P25- P75: 3.511-7.314) days, and 5.695 ( P25- P75: 3.675-7.674) days, respectively. Gamma distribution had the largest log-likelihood result. Conclusions:The distribution of COVID-19 incubation period followed the Gamma distribution, and the interval-censored data estimation method can be used to estimate the incubation period distribution.