ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess， and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 （STAT3）/vascular endothelial growth factor （VEGF） signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine， 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method， with 30 cases in each group. The control group received conventional treatment， while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7^th， 14^th and 21^st day after operation， enzyme-linked immunosorbent assay （ELISA） was used to measure the expression levels of serum interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）. Hematoxylin eosin （HE） staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 （p-STAT3） and vascular endothelial growth factor （VEGF） proteins， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain， secretion volume score， and healing rate of patients on the 3^rd， 7^th， 14^th， and 21^st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group （P<0.05）. For intra-group comparison， the pain score of the control group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The secretion volume score decreased on the 14^th and 21^st days after operation （P<0.05）. The pain score and secretion volume score of the treatment group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The levels of various inflammatory factors decreased in both groups （P<0.05）. Compared with those on the surgical day， the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7^th and 21^st days after operation （P<0.05）. There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period （P<0.01）. For inter-group comparison， on the 7^th and 14^th days after operation， the pain score in the treatment group was lower than that in the control group. On the 7^th， 14^th and 21^st days after operation， the secretion volume scores and healing rate of the treatment group were better than those of the control group （P<0.05）. The levels of various inflammatory factors in the treatment group were lower than those in the control group （P<0.05）， and the decline rate was faster （P<0.05）. On the 7^th day after operation， the levels of p-STAT3， VEGF protein， and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group （P<0.05）. HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly， and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery， reduce secretions， and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β， IL-6， and TNF-α， reducing the inflammatory response of the wound， upregulating the expression of p-STAT3 and VEGF proteins， and stimulating the STAT3/VEGF signaling pathway， thereby accelerating angiogenesis and promoting wound healing.

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.

OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

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.

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.

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.

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.

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.