Colorectal cancer （CRC） ranks as the second leading cause of cancer death worldwide. Although preventive colonoscopy screening has improved the survival rate of CRC patients in the past few years， there are still many patients diagnosed after symptoms appear. The surgery for CRC carries high risks and high recurrence， and ideal therapies remain to be developed. The Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway has become a focus of research due to its central role in cellular activities. As a classic oncogenic pathway， the JAK/STAT signaling pathway offers new possibilities for diagnosing and treating various malignancies， and it paves a new way for developing therapies for CRC. This pathway not only participates in basic cellular processes， such as proliferation， differentiation， and apoptosis but also plays a crucial role in immune responses and inflammation. Abnormal activation of the JAK/STAT signaling pathway is closely related to the occurrence and development of CRC. Studies have shown that the active components and compound prescriptions of traditional Chinese medicine （TCM） can inhibit the proliferation， invasion， migration， and angiogenesis while promoting the apoptosis and autophagy of CRC cells by interfering with the JAK/STAT signaling pathway. Furthermore， this pathway may also play a role in regulating the sensitivity of tumor cells to chemotherapy and radiotherapy， thus influencing the effectiveness of tumor treatment and impeding the progression of CRC. In recent years， research results have been updated rapidly， and previous literature summaries have failed to incorporate the latest findings， creating obstacles to accessing current literature. Therefore， this article supplements and summarizes information from the definition of the JAK/STAT pathway， association of this pathway with CRC， and TCM intervention of CRC. This review aims to provide references for future development of molecular biology regarding CRC and the research and development of new drugs.

BACKGROUND:Combining seed cells with 3D bioprinting technology enables the specific construction of various tissues and organs to meet the demands of tissue repair.However,further research is needed on the promotion of angiogenesis in damaged tissues. OBJECTIVE:By cultivating a 3D scaffold structure of methacrylated gelatin loaded with fibroblasts,obtaining the supernatant,and mixing it in different proportions with a complete culture medium to simulate the cellular microenvironment during tissue repair,this study aimed to explore the role of various cellular microenvironments in promoting angiogenesis in endothelial cells. METHODS:A methacrylated gelatin scaffold structure loaded with fibroblasts was prepared using an extrusion-based 3D bioprinting process.Hydrogel scaffold extract was prepared and mixed with a complete culture medium in ratios of 1:1,1:2,and 1:4 to obtain conditioned medium.Mouse embryonic fibroblasts BALB3T3 and human umbilical vein endothelial cells were co-cultured with complete medium(control group)and hydrogel scaffold extract,respectively.Cell proliferation was assessed using the CCK-8 assay and cell viability was analyzed using live/dead staining.Three kinds of conditioned medium and complete medium(control group)were used to co-culture with human umbilical vein endothelial cells for tube formulation assay,vascular genetic testing,and immunofluorescence staining of CD31. RESULTS AND CONCLUSION:(1)Scanning electron microscopy revealed that the methacrylated gelatin scaffold exhibited a porous structure,and rheological results demonstrated excellent mechanical properties of the hydrogel.CCK-8 assay and live/dead cell staining showed that the hydrogel scaffold extract had no obvious cytotoxicity.(2)Tube formulation assay indicated that the hydrogel showed the total length of cell tubules in 1:1 conditioned medium group was smaller than that in the control group(P<0.05).There were no statistical differences among the four groups in the number of vascular branches formed by endothelial cells(P>0.05).(3)qRT-PCR results showed that for vascular endothelial growth factor mRNA expression,the 1:2 conditioned medium group was lower than the 1:1 conditioned medium group on day 1(P<0.01).On day 3,the expression level of vascular endothelial growth factor in the 1:2 conditioned medium group was higher than that in the control group(P<0.01).On day 5,the cytokine expression level in the 1:2 conditioned medium group was significantly higher than that in the other three groups(P<0.01 or P<0.000 1).The expression in the 1:1 conditioned medium group was significantly lower than that in the other three groups(P<0.05 or P<0.01).On day 1,the expression level of basic fibroblast growth factor in the 1:1 conditioned medium group was significantly higher than that in the control group and 1:4 conditioned medium group(P<0.01,P<0.05).The expression was higher in the 1:2 conditioned medium group than that in the control group(P<0.05).On day 3,the expression levels of cytokines in the 1:4 conditioned medium group was higher than that in the control group(P<0.05).(4)On day 3,the expression of CD31 in the 1:2 conditioned medium group was higher than that in the control group and the 1:4 conditioned medium group(P<0.05).(5)The results indicate that the resulting conditioned media can simulate the microenvironment of vascular regeneration after tissue damage,promoting the vascularization process of endothelial cells.The best promotion of vascularization in endothelial cells was observed when the ratio of supernatant to complete culture medium was 1:2.

Objective:To investigate the efficacy, feasibility, and safety of task-oriented exercise training for hospitalized elderly diabetic patients.Methods:This study is a parallel randomized controlled trial with a positive control and a single-blinded assessor.From July 2020 to July 2021, we included 84 elderly patients with type 2 diabetes who were hospitalized in the Department of Endocrinology at Beijing Hospital.These patients were randomly divided into two groups: the task-oriented exercise training group(TOE group)and the regular exercise training group(regular group). The TOE group participants were trained using a task-oriented exercise program that was specifically developed by our research team.On the other hand, the regular group participants were trained using a classical program that comprised of all exercise modes.Each subject received individualized exercise training for 10 consecutive days while staying in the hospital.We evaluated the efficacy, feasibility, and safety of the training programs by measuring the physical fitness of the participants, assessing the feasibility of the program, and monitoring any exercise-related adverse events that occurred.Results:A total of 79 subjects completed the entire intervention and follow-up period, with 40 subjects in the TOE group and 39 subjects in the regular group.In terms of efficacy, both groups showed improvement in their physical fitness indexes after the intervention, with no significant differences in the degree of improvement between the two groups(all P>0.05). When considering feasibility, the TOE group had a higher proportion of prospective feasibility at 87.5%(35 out of 40)compared to the regular group at 71.8%(28 out of 39). Similarly, the TOE group had a higher proportion of practical feasibility at 75.0%(30 out of 40)compared to the regular group at 53.8%(21 out of 39). The TOE group showed a significant advantage in practical feasibility between the two groups( χ2=3.862, P=0.049). As for safety, there were no exercise-related adverse events during the intervention in either group. Conclusions:The efficacy and safety of the task-oriented exercise program for hospitalized elderly diabetic patients is comparable to that of the regular program.Additionally, the task-oriented program is more feasible than the regular program.

Objective: To investigate the differences in enolase and laminin levels in vaginal epithelial tissues between mice successfully infected withGardnerellaand mice not infected with Gardnerella, providing information for further exploration of the correlation between enolase and laminin levels and the incidence of bacterial vaginosis. Methods: Gardnerella strains isolated, purified, and identified from vaginal secretions of patients with bacterial vaginosis were used to infect the vagina of mice and establish a mouse model of bacterial vaginosis. Successful and failed mice was defined as successful and failed groups, respectively. Differential expression of enolase and laminin in the vaginal epithelial tissue of two groups of mice was detected by Western blot. Modeling success rate was statistically analyzed, and the expression differences of enolase and laminin was compared between two groups. Results: One strain of Gardnerella vaginalis infected 10 SPF grade KM mice, 7 mice met the diagnostic criteria for bacterial vaginosis, and 3 mice failed to model, with a success rate of 70%. Western blot was used to detect protein expression levels, and the levels of laminin and enolase in the successfully modeled mouse vaginal epithelial tissue were significantly higher than those in the failed modeling group, with statistical differences between the two groups(P<0.05). Conclusion Enolase and laminin may be involved in the occurrence of bacterial vaginosis, however, further research is needed to determine the mechanisms through which they trigger the occurrence and development of the disease.

Objective To investigate the nutritional status and dietary structure of tuberculosis patients among dif-ferent populations, analyze the factors influencing the nutritional status of tuberculosis patients, and provide theo-retical basis for improving clinical nutrition and related issues in tuberculosis patients.Methods Tuberculosis pa-tients, non-tuberculosis patients, and healthy individuals were randomly selected for a questionnaire survey.De-scriptive analysis was conducted using SPSS 20.0 software.Statistical description was performed using rates and composition ratios, and qualitative data were described using relative numbers.Chi-square test was used to compare overall rates and composition ratios among different health conditions groups, with a significance level of α=0.05.Independent factors analysis of nutritional status body mass index (BMI) was conducted using multiple Logistic re-gression analysis for variables with statistically significant differences in the univariate analysis.Results There were differences in the nutritional status (x2 =62.184, P<0.05) and dietary diversity score (x2 =64.049, P<0.05) among tuberculosis patients, non-tuberculosis patients, and healthy individuals.Univariate analysis of nutri-tional status BMI showed statistically significant differences in gender, smoking, meat-based diet, vegetable-based diet, moderate diet diversity score, and 6 other variables for tuberculosis patients (P <0.05) , and in gender, age, ethnicity, marital status, occupation, education level, smoking, drinking white wine, drinking beer, meat-based diet, moderate diet, and 11 other variables for healthy individuals (P<0.05) .The variables with statisti-cally significant differences in the univariate analysis were included in the multiple ordinal logistic regression analy-sis model for both tuberculosis patients and healthy individuals.The results showed that the level of education, veg-etable intake, moderate food diversity score (DDS) of 4-6 were independent influencing factors of nutritional sta-tus BMI among tuberculosis patients (P<0.05);marital status was an independent influencing factor of nutritional status BMI among non-tuberculosis patients (P<0.05);while gender and occupation were independent influencing factors of nutritional status BMI among healthy individuals (P<0.05).Conclusion The dietary nutritional status of the three population groups varied.Targeted health education should be conducted, especially for tuberculosis patients, to address the issue of uneven dietary intake and promote good dietary habits among local tuberculosis pa-tients.

Objective To investigate the status quo of drug resistance and influencing factors of tuberculosis in In-ner Mongolia,and to provide reference for accurate prevention and control of drug-resistant tuberculosis.Methods Random sampling was used in this study.TB patients from Tuberculosis designated hospital in Inner Mongolia were included,according to the rules and drug-resistant strains were identified and tested according to relevant norms.Composition ratio or rate was calculated for statistical description,and Logistic regression model was used to analyze the influencing factors of drug resistance in TB patients.Results Among 1 321 patients,there were 936 males and 385 females,with an average age of(52.65±18.09)years.The rates of mono-resistant,multidrug-resistant(MDR),extensively drug-resistant(XDR)and total drug resistance were 19.00%,11.58%,11.66%and 42.24%,respectively.The highest resistance rates were observed for streptomycin(7.27%),isoniazid(4.69%),and isoniazid+streptomycin(4.47%).The drug resistance spectrum presented diversity and com-plexity.Compared to females,males had a higher proportion of drug resistance,and the difference was statistically significant(P<0.001).The proportion of patients who were sensitive to anti-tuberculosis drugs increased with age(P<0.05).Among different age groups,the proportion of drug-resistant patients was higher in the 20-40 age group,40-60 age group,and 60 and above age group compared to the 0-20 age group(P<0.05).Addi-tionally,the proportion of drug-resistant patients was higher in the 20-40 age group and 40-60 age group com-pared to the 60 and above age group(P<0.05).Moreover,the proportion of drug-resistant and multi-drug re-sistant patients was higher among patients undergoing retreatment compared to those undergoing initial treatment(P<0.001).Multivariate Logistic regression analysis showed that male gender(OR=1.48,95%CI:1.02-2.14),age 20-40 years(OR=2.64,95%CI:1.05-6.60),retreatment(OR=2.34,95%CI:1.70-3.22),and outpatient follow-up(OR=1.56,95%CI:1.05-2.33)were independent risk factors for drug-resistant tuber-culosis.Conclusion Inner Mongolia has a high prevalence of MDR and overall drug-resistant tuberculosis among patients.The drug resistance profile exhibits diversity and complexity.Risk factors that contribute to drug resist-ance include being male,aged between 20 and 40,undergoing retreatment,and receiving outpatient follow-up.Therefore,it is necessary to further improve clinical diagnosis and treatment,promote rational use of first-line anti-tuberculosis drugs,prioritize individualized treatment,enhance health education,improve the medical insurance system,and optimize patient management approaches in order to enhance patient compliance.

Objective:To investigate the efficacy of different doses of bortezomib combined with chemotherapy for multiple myeloma (MM).Methods:A prospective case series study was performed. A total of 81 MM patients at Leshan People's Hospital from February 2022 to May 2023 were collected as study subjects. According to the random number table method, patients were divided into high-dose bortezomib group (39 cases treated with 1.6 mg/m 2 bortezomib combined with dexamethasone and thalidomide) and low-dose bortezomib group (42 cases treated with 1.3 mg/m 2 bortezomib combined with dexamethasone and thalidomide). The clinical efficacy after 4 courses of treatment, adverse reactions, C-reactive protein (CRP), β 2 microglobulin (β 2-MG) and serum creatinine levels before and after treatment, survival and prognosis of patients in both groups were compared. Results:There were 29 males and 10 females in the high-dose bortezomib group and the age was (59±5) years; there were 31 males and 11 females in the low-dose bortezomib group and the age was (59±6) years. The differences in the general data of both groups were statistically significant (all P > 0.05). The overall effectiveness rate was 87.2% (34/39) and 80.9% (34/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 0.58, P = 0.446). The incidence rate of adverse reactions was 30.8% (12/39), 19.0% (8/39), respectively in the high-dose bortezomib group and the low-dose bortezomib group, and the difference was not statistically significant of both groups ( χ2 = 1.49, P = 0.222). Before treatment, there were no statistically significant differences in the levels of CRP, β 2-MG and serum creatinine between the 2 groups (all P > 0.05); after treatment, there were statistically significant differences in the levels of CRP [(23.6±2.2) g/L vs. (31.5±3.6) g/L)], β 2-MG [(2 317±63) μg/L vs. (4 212±114) μg/L] and serum creatinine [(70±5) μmol/L vs. (79±7) μmol/L] in the high-dose bortezomib group and the low-dose bortezomib group ( t value was 4.28, 18.29, 4.00, all P<0.05); and the levels of above 3 indicators after treatment were lower than those before treatment of both groups (all P < 0.05). The mortality rate was 10.3% (4/39) and 14.3% (6/42), respectively in the high-dose bortezomib group and the low-dose bortezomib group 1-year follow-up after treatment, and the difference was not statistically significant ( χ2 = 0.30, P = 0.582). Conclusions:The efficacy and safety of high-dose bortezomib combined with chemotherapy are comparable to those of low-dose bortezomib combined with chemotherapy in treatment of MM, while the former could improve renal function and inflammatory status of MM patients.

Objective : To select and obtain vaginal Lactobacillus strains with inhibitory effect on Gardnerella vagi⁃ nalis , and to explore the possible mechanism of inhibition of Gardnerella vaginalis by Lactobacillus vaginalis strains , so as to provide a prerequisite for the development of dominant strains for human disease treatment. Methods : Gardnerella vaginalis and vaginal Lactobacillus strains were isolated from vaginal secretions of patients with bacterial vaginosis (BV) and healthy women , respectively. The Lactobacillus strains with the ability to inhibit the proliferation of Gardnerella vaginalis were screened by spot on lawn. Double agar diffusion method was used to compare the inhibitory effects of Lactobacillus solutions , cell⁃free culture supernatants (CFCs) and bacteria on Gardnerella vaginalis. Results : Sixty⁃two strains of vaginal Lactobacillus strains were isolated and purified from vaginal vaginal secretions of 10 patients with bacterial vaginosis. Among the 62 strains of vaginal Lactobacillus , 18 strains could inhibit the proliferation of Gardnerella vaginalis. The vaginal Lactobacillus solutions , the CFCs , and bacteria all had inhibitory effect on Gardnerella vaginalis. The inhibitory effects of vaginal Lactobacillus solutions were higher than those of the CFCs. After the CFCs were treated with proteinase K , the inhibitory effect of eight samples disappeared , and that of 10 samples weakened obviously. Conclusion In this paper, 62 vaginal Lactobacillus strains are purified and identified , of which 18 strains can inhibit the proliferation of Gardnerella vaginalis. The production of antimicrobial protein may be involved in the mechanism that vaginal Lactobacillus inhibits the proliferation of Gardnerella vaginalis.

ObjectiveTo evaluate the Chinese guidelines and consensus of rehabilitation medicine published in the medical journals in 2022 using Scientific, Transparent and Applicable Rankings (STAR). MethodsGuidelines and consensus which were developed by Chinese institutions or led by Chinese scholars were retrieved in databases of CNKI, Wanfang Data, CBM, Chinese Medical Journal Network, PubMed and Web of Science, in 2022, followed by screening for rehabilitation medicine field. The literature were rated with STAR. ResultsSeven guidelines and eleven consensuses were included. The STAR scores ranged from 11.7 to 69.6, with a median score of 25.9 and mean score of 28.3. There was a significant difference in the total score between guidelines and consensus (U = 12.000, P = 0.014). The score ratio was high in the domains of recommendations (73.6%), evidence (39.5%) and others (33.3%), while it was low in the domains of protocol (1.4%), clinical questions (12.5%) and conflicts of interest (13.9%). The score ratio was high in the items of listing the institutional affiliations of all individuals involved in developing the guideline (94.4%), identifying the references for evidence supporting the main recommendations (94.4%), indicating the considerations (e.g., adverse effects) in clinical practice when implementing the recommendations (88.9%), and making the recommendations clearly identifiable, e.g., in a table, or using enlarged or bold fonts (75%); and it was low in the items of describing the role of funder(s) in the guideline development (0), indicating information about the evaluation and management of conflicts of interest (0), providing tailored editions of the guidelines for different groups of target users (0), presenting the guideline or recommendations visually, such as with figures or videos (0), providing details of the guideline protocol (2.8%), assessing the risk of bias or methodological quality of the included studies (2.8%), describing the responsibilities of all individuals or sub-groups involved in developing the guideline (5.6%), indicating how the clinical questions were selected and sorted (5.6%), formating clinical questions in PICO or other formats (5.6%), making the guideline accessible through multiple platforms (5.6%), and declaring that the funder(s) did not influence the guideline's recommendations (8.3%). ConclusionThe quality of current clinical practice guidelines and consensus of rehabilitation medicine is poor, which should be developed in accordance with the relevant standards.

OBJECTIVE: To explore the genetic basis for a child featuring complex cortical dysplasia and other brain malformations (CDCBM3). METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out for the family trio. Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 1-year-and-2-month old Chinese boy, had presented with motor developmental delay, lissencephaly, severe cognitive impairments, absent speech and congenital laryngomalacia. WES revealed that he has harbored a heterozygous missense variant of the KIF2A gene, namely NM_001098511.2: c.952G>A, p.Gly318Arg (GRCh37/hg19). The highly conserved residue is located around the ATP nucleotide-binding pocket in the kinesin motor domain (PM1). The variant was not found in the Genome Aggregation Database and the 1000 Genomes Project (PM2), and was predicted to be deleterious on the gene product by multiple in silico prediction tools (PP3). This variant was unreported previously and was de novo in origin (PS2). Based on the ACMG guidelines, it was categorized as likely pathogenic (PS2+PM1+PM2+PP3). Furthermore, the congenital laryngomalacia found in our patient was absent in previously reported CDCBM3 cases. CONCLUSION The novel variant of the KIF2A gene probably underlay the disorders in the proband. Above finding has expanded the phenotypic and mutational spectrum of CDCBM3.
Asians/genetics* ; Brain ; China ; Humans ; Infant ; Kinesins/genetics* ; Male ; Malformations of Cortical Development/genetics* ; Whole Exome Sequencing