Objective To investigate the preparation process of cold -dampness medicine iron stick and the curative effect of cold -dampness medicine iron stick,thus to provide reference for the clinical treatment of cold -dampness lumbago.Methods Using science and technology of preparation and the thermal effect of cold -dampness medicine iron stick was observed.1 20 cases with cold -dampness lumbago of dampness type with low back pain, according to the order of treatment were divided into the observation group and control group.63 cases of the treatment group were given cold -dampness medicine iron stick affixed to the surface of the skin,57 cases of the control group were given kanlisha affixed to the surface of the skin.The treatment effect after one course of treatment was observed. Results Cold -dampness medicine iron stick heat effect index of heat time was 1 2min,to thermal time was 1 0.8h, the highest temperature was 56.5℃,thermal equilibrium curve was gentle and lasting.The efficacy of the two groups of drugs within the observation time effect was obvious.The total effective rate of the observation group was 90.5%(57 /63),which was higher than 75.4%(43 /57)of the control group,the difference was statistically significant (χ2 =4.87,P <0.05).During the treatment,local skin blisters,rash,itching and other low temperature burns and other allergic reaction were not found.Conclusion Cold -dampness medicine iron stick process is stable and controllable in quality and heat balance curve slow long -lasting,determine the efficacy,innovative therapies,it is easily accepted by patients and worthy to be popularized in clinical practice.

Tuochuang Shengji therapy (the therapy of supporting sores and generating muscle) belongs to the "tonic method" of internal treatment of TCM surgical sores and ulcers. Its meaning is to strengthen the healthy qi and discharge purulent, remove the rot and promote the growth of the muscle. The representative prescriptions include Tuoli Xiaodu Powder, Huangqi Decoction, Painong Neituo Powder, Shengong Neituo Powder, etc., mostly with Astragali Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Angelicae Sinensis Radix and other tonic drugs, supplemented by Gleditsiae Spina, Lonicerae Japonicae Flos and other anti-pathogenic factor drugs to strengthen the the healthy qi and discharge purulent. The main mechanism of Tuochuang Shengji method in the treatment of refractory wounds include anticoagulation in the hemostasis stage, anti-inflammation and bacteriostasis in the inflammation stage, promoting angiogenesis in the proliferation stage, and promoting granulation tissue growth and re-epithelialization in the remodeling stage. The existing research on the understanding of Tuochuang Shengji therapy is mostly the method of tonifying qi and supporting sores, and there is few related literature on the remaining treatment methods. In the future, the integrity and systematicness of TCM should be paid attention to, the multi-component analysis of Tuochuang Shengji compound and the continuous research on the upstream and downstream of signaling pathways should be strengthened, the quality of research should be improved.

Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Toll-like receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or vi-ruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.

Objective:To investigate the efficacy and safety of chidamide in the maintenance therapy for patients with T-cell lymphoma (TCL).Methods:A prospective, single-arm clinical study was conducted. A total of 53 TCL patients who achieved partial remission (PR) and above after first-line induction chemotherapy in the Second Affiliated Hospital of Army Military Medical University from May 2018 to July 2020 were included, among which 28 cases underwent autologous hematopoietic stem cell transplantation after induction chemotherapy, and then received maintenance therapy with chidamide initiating 30 to 45 days after transplantation (the transplantation group); 25 cases began to receive maintenance therapy with chidamide about 30 days after 6 to 8 courses of first-line induction chemotherapy (non-transplantation group). Chidamide usage was listed as follows: oral, 20-30 mg per time, 2 times per week, at intervals of not less than 3 d and the therapy was maintained for 2 years or until disease progression or intolerance. The main study endpoint was the 2-year recurrence rate, and the secondary study endpoints included the 1-year recurrence rate, the 1- and 2-year progression free survival (PFS) rate, the 1- and 2-year overall survival (OS) rate, and the safety of maintenance therapy.Results:The median follow-up was 13.5 months (range 5 to 51 months). After 6 to 8 courses of first-line induction chemotherapy in 53 patients with TCL, complete remission (CR) was achieved in 29 (54.7%) cases and PR in 24 (45.3%) cases. The proportion of patients aged ≤ 60 years and those achieving CR before maintenance treatment in the transplantation group was higher than that in non-transplantation group (both P < 0.05). During maintenance therapy, the best remission reached CR in 84.9% (45/53) of patients; CR rates during maintenance therapy were 89.3% (25/28) and 80.0% (20/25), respectively in the transplantation and non-transplantation groups; and PR rates were 10.7% (3/28), and 20.0% (5/25) ( χ2 = 0.31, P = 0.577). Among the 53 patients with TCL, 21 cases had recurrence with a 1-year recurrence rate of 26.4% (14/53) and a 2-year recurrence rate of 39.6% (21/53). The 2-year recurrence rates were 42.9% (12/28) and 36.0% (9/25), respectively in the transplantation and non-transplantation groups, and the difference was not statistically significant ( χ2 = 0.26, P = 0.610). The 1-year recurrence rates of patients receiving chidamide maintenance therapy with different international prognostic index (IPI) scores and whether achieving CR before maintenance therapy or not showed statistically significant differences (all P < 0.05); the 2-year recurrence rates of patients receiving chidamide maintenance therapy with different IPI scores, bone involvement or not and whether achieving CR before maintenance therapy or not showed statistically significant differences (all P < 0.05). The 1-year PFS and OS rates were 80.7% and 88.6%, and the 2-year PFS and OS rates were 61.1% and 71.9% in 53 patients. The 1-year PFS rates of patients in the transplantation and non-transplantation groups were 81.1% and 80.2% ( P = 0.774), and the 1-year OS rates were 89.3% and 87.4%, respectively ( P = 0.736). The 2-year PFS rates were 60.4% and 61.3% ( P = 0.440), and the 2-year OS rates were 72.7% and 70.6% ( P = 0.510). No patient discontinued chidamide maintenance therapy due to adverse drug reactions during maintenance therapy; ≥ grade 3 adverse drug reactions included neutropenia (9 cases, 23.1%), anemia (7 cases, 17.9%), thrombocytopenia (6 cases, 16.2%) and electhrolyte disturbance (1 case, 5.3%). The chidamide dosage was adjusted to 20 mg per time due to leucopenia in 7 patients and thrombocytopenia in 3 patients. Conclusions:Maintenance therapy with chidamide can reduce recurrence rate and prolong survival time of TCL patients, and it has a favorable safety.

Peripheral T-cell lymphoma(PTCL)is a group of hematological malignant tumors with high heterogeneity.At present,CHOP(cyclophosphamide,vincristine,prednisone,doxorubicin)or CHOP-like regimens are usually used for first-line treatment,but the remission rate is low,and the prognosis is poor.It is urgent to improve the traditional chemotherapy regimens to improve the efficacy onthe basis of tradtional che-motherapeutic regimen.Recent studies have found that the epigenetic alterations are crucial in the pathogene-sis of PTCL,and more and more new epigenetic targeted drugs have shown good effects and safety in the monotherapy and combination therapy of PTCL,which provide a new strategy for the precise diagnosis and treatment of PTCL.This article reviews the latest progress in epigenetic changes of PTCL and the prospects of targeted drug therapy applications,in order to provide reference for improving the clinical prognosis of the patients with PTCL.

Ruxolitinib， a small molecule inhibitor， selectively targets Janus kinase （JAK） by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain， thereby inhibiting JAK activation and signal transducer and activator of transcription （STAT） phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream， approved by the US FDA as the first non-segmental vitiligo home treatment drug， is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis， alopecia areata， and other conditions， indicating great application prospects.

The accurate annotation of transcription start sites(TSSs)and their usage are critical for the mechanistic understanding of gene regulation in different biological contexts.To fulfill this,specific high-throughput experimental technologies have been developed to capture TSSs in a genome-wide manner,and various computational tools have also been developed for in silico pre-diction of TSSs solely based on genomic sequences.Most of these computational tools cast the problem as a binary classification task on a balanced dataset,thus resulting in drastic false positive predictions when applied on the genome scale.Here,we present DeeReCT-TSS,a deep learning-based method that is capable of identifying TSSs across the whole genome based on both DNA sequence and conventional RNA sequencing data.We show that by effectively incorporating these two sources of information,DeeReCT-TSS significantly outperforms other solely sequence-based methods on the precise annotation of TSSs used in different cell types.Furthermore,we develop a meta-learning-based extension for simultaneous TSS annotations on 10 cell types,which enables the identification of cell type-specific TSSs.Finally,we demonstrate the high precision of DeeReCT-TSS on two independent datasets by correlating our predicted TSSs with experimentally defined TSS chromatin states.The source code for DeeReCT-TSS is available at https://github.-com/JoshuaChou2018/DeeReCT-TSS_release and https://ngdc.cncb.ac.cn/biocode/tools/BT007316.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group， model group and T. mongolicum total flavonoid group， with 8 mice in each group. Except for the blank group， the other 2 groups were given a high-fat diet， while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/（kg·d）] intragastrically， once a day， for 8 consecutive weeks. During the experiment， the food intake of each group of mice was recorded. After the last medication， the body mass， fat weight， blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing； the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group， the body weight of mice in T. mongolicum total flavonoids group was decreased significantly （P＜0.05）； the levels of total lipid cholesterol， triglycerides， and LDL cholesterol were all decreased significantly （P＜0.01）， and the level of HDL cholesterol was increased significantly （P＜0.01）； the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced （P＜0.05）； significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved； mRNA expressions of COX7A1 and COX8B were significantly upregulated （P＜0.05）. The results of bacterial colony detection showed that compared with the model group， there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group， and the Sobs index characterization and β diversity were increased significantly （P＜0.05）. Relative abundances of Blautia， norank_f_Ruminococcaceae， Bilophila， Alistipes， classified_f_Ruminococcaceae， Parabacteroides， norank_f_Desulfovibrionaceae， Anaerotruncus were significantly up-regulated（P＜0.05）， while those of Faecalibaculum， Erysipelatoclostridium， GCA-900066575， Tuzzerella， Lactobacillus， norank_f_norank_o_RF39， achnospiraceae_FCS020_group were significantly down-regulated （P＜0.05）. CONCLUSIONS T. mongolicum total flavonoids can reduce body mass， fat weight and blood lipid levels， and repair the pathological damage to liver and epididymal fat in obese mice， which is related to improving intestinal flora disorders caused by high-fat diet.