Colitis-associated cancer(CAC)is a specific type of colorectal cancer that develops from inflammatory bowel disease(IBD).Myeloid-derived suppressor cells(MDSCs)are a group of myeloid cells with immunosuppressive properties,and MDSCs in the tumor microenvironment proliferate and activate during the development of colitis-associated cancer,inhibiting T-cell production and impairing their function,which impedes the immunotherapeutic effect of colitis-associated cancer.In this paper,we review the immunosuppressive mechanisms of MDSCs in the development of inflammatory bowel disease to colitis-associated cancers and the current drugs targeting MDSCs for immunotherapy of inflammatory colorectal cancers,with a view to providing new strategies for the treatment of colitis-associated cancers.

Objective To investigate the effects of cinbufagin(CB)on the proliferation,migration and invasion ability as well as epithelial-mesenchymal transition(EMT)of human colon cells HCT116.Methods Logarithmically grown HCT116 cells were randomly divided into blank group and experimental-L,-M,-H groups;the blank group did not receive any treatment(0 nmol·L-1),and experimental-L,-M,-H groups were cultured in 1 640 medium containing 17.5,35 and 70 nmol·L-1 cinbufagin for 48 h.Cell counting kit-8(CCK-8)was used to detect the effect of cinbufagin on the survival rate of HCT116 cells;cloning assay was used to detect the effect of cinbufagin on the proliferation of HCT116 cells;cell scratch assay and Transwell assay were used to detect the effect of cinbufagin on the migration and invasive ability of HCT116 cells;Western blot was used to detect the expression levels of janus kinase 2(JAK2)/signal transducers and activators of transcription 3(STAT3)pathway and EMT-related proteins of HCT116 cells.Results The number of clone formation in blank group and experimental-L,-M,-H groups were 122.67±24.42,73.67±15.82,44.33±4.51 and 21.67±1.53;the rates of migration of scratches were(44.64±9.15)％,(26.91±2.94)％,(19.28±1.52)％and(6.33±2.30)％;the number of invaded cells were 120.33±1.15,58.33±9.07,33.33±1.53 and 18.33±3.21;the relative protein expression of phosphorylated JAK-2(p-JAK-2)/JAK-2 were 1.02±0.06,0.94±0.05,0.75±0.22 and 0.49±0.22;relative protein expression of phosphorylated STAT3(p-STAT3)/STAT3 were 0.89±0.10,0.72±0.04,0.65±0.06 and 0.52±0.18;relative protein expression of E-cadherin were 0.30±0.14,0.41±0.13,0.49±0.14 and 0.69±0.17;relative protein expression of N-cadherin were 0.96±0.11,0.78±0.04,0.69±0.12 and 0.40±0.15;Snail relative protein expression were 0.89±0.08,0.62±0.15,0.44±0.15 and 0.27±0.09;Vimentin relative protein expression were 0.92±0.09,0.76±0.13,0.63±0.01 and 0.43±0.09,respectively.The above indexes in experimental-H group showed statistically significant differences compared to blank group(all P＜0.05).Conclusion HCT116 can inhibit the invasion and metastasis of human colorectal cancer cells HCT116 by inhibiting epithelial-mesenchymal transition through JAK2/STAT3 pathway.

Objective To explore the mechanism of inhibition of colorectal cancer cells HT29 proliferation,migration and invasion by bufalin through Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods Human colorectal cancer HT29 cells were randomly divided into control group and experimental-L,-M,-H groups.The cells in the control group were not treated,and the cells in the experimental-L,-M,-H groups were treated with 2.5,5.0 and 10.0 μmol·L-1 bufalin for 48 h.After HT29 cells were infected with FLAG STAT3 lentivirus,the cells were divided into lentivirus infection group and experiment-H(10.0 pmol·L-1 bufalin)+lentivirus infection group.Cell viability was detected by cell counting kit 8(CCK-8).Cloning experiment to verify cell proliferation rate;Transwell experiment verified the migration ability of cells after bufalin treatment;the transfection efficiency of lentivirus and the expression of cell-related proteins were detected by Western blot.Results After 48 h of drug action,the number of cells in the control group,experimental-L,-M,-H groups were 1 003.25±255.53,698.00±152.25,562.13±31.56 and 449.50±82.40,respectively;the number of invasive cells were 932.00±188.84,742.22±108.64,514.67±124.82 and 343.56±86.42,respectively;the protein expression level of p-JAK2 were 1.37±0.27,0.97±0.06,0.74±0.06 and 0.39±0.12,respectively.The number of cells in the control group,experimental-H group,lentivirus infection group,and experimental-H+lentivirus infection group were 906.88±211.71,389.00±143.08,1 279.38±210.34 and 604.75±12.52,respectively;the number of invasive cells were 671.22±44.74,246.11±28.16,1 080.78±119.13 and 574.78±16.23,respectively.Compared with the control group,there were statistically significant differences in the number of cell proliferation,the number of cell invasion and the relative levels of p-JAK2 in the experimental-M and-H groups(all P＜0.05).Compared with the control group,the number of cell proliferation and the number of cell invasion in the experimental-H group,the lentivirus infection group,and the high-dose experimental+lentivirus infection group were statistically significant(all P＜0.05).Conclusion Bufalin can inhibit the proliferation,migration and invasion of colorectal cancer by activating the JAK2/STAT3 signalling pathway.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Leclercia adecarboxylata is a Gram-negative bacterium belonging to the Enterobacteriaceae family. To our knowledge, this is the first report of a carbapenem-resistant L. adecarboxylata strain isolated from a healthy newborn. The L. adecarboxylata strain isolated in this study carried four plasmids that may serve as reservoirs for antibiotic resistance genes. Plasmids 2 and 4 did not harbor any antimicrobial resistance genes. Plasmid 3 is a novel plasmid containing three resistance genes. The bla _IMP gene harbored in the strain was most similar to bla _IMP-79 at the nucleotide level, with a similarity of 99.4% (737/741). This case highlights the importance of considering L. adecarboxylata as a potential cause of infections in children.
Infant, Newborn ; Child ; Humans ; Female ; Enterobacteriaceae Infections/microbiology* ; Enterobacteriaceae/genetics* ; Anti-Bacterial Agents/therapeutic use* ; Plasmids

Abstract: To analyze the clinical, therapeutic and laboratory characteristics of disseminated cryptococcosis caused by Cryptococcus neoformans invading the blood stream in patient with liver cirrhosis and splenectomy. A 30-year-old male underwent splenectomy plus pericardial devascularization due to "splenomegaly and hypersplenism" in March in 2016. The patient had intermittent fever after operation for many times, and successively accompanied with back pain, left lower limb abscess and right hip pain. The highest body temperature was 39 ℃. CT and MRI revealed the lung lesion and multiple bone destruction. During that period, the effect of antibiotics was not good. On April 19th, 2017, Gram's stain, India ink stain, API 32C, Vitek 2 Compact, ribosomal ITS and IGS sequence analysis were performed to identify the strain isolated from the pus and blood stream. The serum of the patient was detected for cryptococcal antigen. Antifungal susceptibility test was used to determine drug sensitivity and minimum inhibitory concentration (MIC). The Cryptococcus neoformans isolated from fresh pus specimen showed a prominent, thick capsule after India ink stain. The colonies isolated from pus and blood stream were identified Cryptococcus neoformans using API 32C, Vitek 2 Compact, and sequence analysis of rDNA ITS and IGS. Cryptococcal capsule antigen was positive. The minimal inhibitory concentrations of 5-Flucytosine, amphotericin B, fluconazole, itriconazole, voriconazole against the isolate were <4 μg/mL, <0.5 μg/mL, 4 μg/mL, ≤0.25 μg/mL, 0.125 μg/mL respectively. The patient was initially treated with intravenous amphotericin B and flucytosine. After anti-Cryptococcus treatment for two months, the patient clinically improved, and the lesions were reduced on a follow-up CT scan. The patient made a full functional recovery after treatment for six months. Cryptococcosis has hidden onset, atypical clinical symptoms and lack of specificity. Blood stream is the main channel for Cryptococcus to spread and involve many organs of the whole body, including skin, bone and so on. Therefore, early use of blood culture to monitor blood flow dissemination, actively removing the primary focus and cutting off the infection route in time and carrying out effective anti-Cryptococcus treatment are conducive to the patient's early recovery.

OBJECTIVE: To explore clinical effect of the first metatarsophalangeal joint fusion combined with lateral toe rotation Weil osteotomy in treating hallux valgus with severe metatarsal adduction. METHODS: From March 2017 to August 2021, 37 patients ( 69 feet ) with severe plantar adductor hallux valgus were treated with the first metatarsophalangeal joint fusion combined with rotational Weil osteotomy were retrospectively analyzed, including 8 males(11 feet) and 29 females (58 feet), aged from 67 to 83 years old with an average of (70.03±2.87) years old;3 cases on the left side, 2 cases on the right side and 32 cases on both sides. Visual analogue scale(VAS) was used to evaluate degree of pain relief before operation, 6 weeks after operation and at the final follow-up. American Orthopaedic Foot and Ankle Surgery (AOFAS) forefoot score was used to evaluate function of the affected foot before operation and final follow-up. Hallux valgus angle(HVA) and intermetatarsal angle(IMA) were measured before operation and at the final follow-up. RESULTS: Thirty-seven patients(69 feet) were followed up from 12 to 48 months with an average of(22.8±0.6) months. Bone healing was achieved at the first metatarsophalangeal joint from 7 to 10 weeks with an average of (8.00±1.21) weeks after operation, without delay and nonunion. HVA was increased from (44.30±2.84)° before operation to (15.20±2.13) °at the final follow-up, and had statistical difference(t=65.781, P<0.05);while no difference in IMA before and after operation(P>0.05). VAS was decreased from (6.73±1.48) points to (2.78±0.71) points at 6 months after operation(t=3.279, P<0.05), and had difference compared with the latest follow-up(1.16±1.12)(t=4.859, P<0.05). AOFAS forefoot score increased from (52.14±5.78) preoperatively to (86.70±4.86) at the fonal follow-up, and 25 feet got excellent results, 40 feet good and 4 feet fair. CONCLUSION The first metatarsophalangeal joint fusion combined with lateral toe rotation Weil osteotomy in treating severe plantar adduction hallux valgus could significantly relieve pain and appearance of forefoot, stabilize the first sequence, and significantly improve walking function.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Metatarsal Bones/surgery* ; Hallux Valgus/surgery* ; Retrospective Studies ; Rotation ; Treatment Outcome ; Osteotomy/methods* ; Metatarsophalangeal Joint/surgery* ; Bunion ; Toes

OBJECTIVE: To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors. METHODS: A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children. RESULTS: Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%. CONCLUSIONS Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.
Child ; Family ; Humans ; Kidney Neoplasms/therapy* ; Progression-Free Survival ; Retrospective Studies

Objective:To review and summarize the current research status of traditional Chinese medicine（TCM） for the treatment of chronic atrophic gastritis（CAG），provide references and hints for relevant studies，and contribute to the further understanding of TCM and the application of TCM in the treatment of CAG with scientific evidence. Method:The PubMed and Web of Science databases were searched for relevant literature on the treatment of CAG with TCM from their establishment to August 31，2020. Eligible randomized controlled trials （RCTs） and animal studies were included according to the inclusion and exclusion criteria，and then the information of the included studies was extracted，summarized，and organized for further analysis. Result:A total of 4 RCTs and 21 animal studies （including 13 papers on compound studies，3 papers on single herb studies，and 5 papers on monomer studies） about TCM treatment for CAG were included in this study. RCTs showed that TCM could work well in improving the pathological state of gastric mucosa and clinical symptoms in patients. However，there were problems of low study quality，and non-uniform diagnostic criteria for gastric mucosal pathology and clinical efficiency evaluation. Animal experiments mainly focused on the study of drug mechanism exploration，and their results showed that TCM treatment of CAG was characterized by multi-target action. However，the animal experiments also had some problems such as inconsistence of CAG animal model establishment，positive drug selection，drug intervention methods as well as intervention cycles among different experiments. Conclusion:The efficacy of TCM in the treatment of CAG has gradually gained global recognition，but there is still a need for further standardization and unification of research methods. In the future，high-quality clinical trials and standardized animal experiments are still needed to conduct in-depth studies on the time for intervention，intervention methods，active ingredients and mechanisms of TCM，so as to make contributions to the full understanding and application of TCM in the treatment of CAG.