ObjectiveTo classify subtypes among middle-aged and elderly type 2 diabetes mellitus (T2DM) patients aged between 35‒74 years in Shanghai suburbs, to compare their characteristics and analyze incidence risk for cerebrovascular disease among these subtypes, so as to promote personalized and precise treatment of T2DM. MethodsA total of 7 792 patients with T2DM who completed a baseline survey from 2016 and 2019 were selected as the research subjects, based on the data from a natural population cohort and biobank in Shanghai suburbs. Patients were stratified by gender and clustered into subtypes using k-means method based on baseline parameters including the age at T2DM diagnosis, body mass index (BMI), fasting blood glucose, and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Patients were followed up until March 31, 2023. Multivariate Cox regression models were used to analyze the association between subtypes and incidence risk for cerebrovascular disease, and those with cerebrovascular disease within 1 year of follow-up survey were excluded from sensitivity analysis. ResultsAmong the 7 792 patients with T2DM, 3 615 were males and 4 177 were females. Stratified by gender, 4 subgroups were identified through k-means clustering analysis, namely poor blood glucose control subgroup, severe insulin-resistant subgroup, younger onset subgroup, and older onset subgroup. The median follow-up time was 4.30 years, during which 1 960 cerebrovascular disease events were observed (844 in males, 1 116 in females). After adjusting for smoking, alcohol consumption, weekly exercise, family history of diabetes mellitus, and duration of diabetes mellitus, among male patients, the incidence risk for cerebrovascular disease was lower in the younger onset subgroup (HR=0.59, 95%CI: 0.48‒0.73, P<0.001), poor blood glucose control subgroup (HR=0.81, 95%CI: 0.65‒1.00, P=0.046), and severe insulin-resistant subgroup (HR=0.61, 95%CI: 0.50‒0.75, P<0.001), compared to the older onset subgroup. While among female patients, the incidence risk for cerebrovascular disease was also lower in the younger onset subgroup (HR=0.68, 95%CI: 0.57‒0.80, P<0.001), poor blood glucose control subgroup (HR=0.73, 95%CI: 0.60‒0.89, P=0.002), and severe insulin-resistant subgroup (HR=0.72, 95%CI: 0.61‒0.85, P<0.001), compared to the older onset subgroup. Results of the sensitivity analysis were consistent with the main findings. ConclusionAmong middle-aged and elderly T2DM patients in suburban Shanghai, both male and female patients have the highest incidence risk for cerebrovascular disease in the older onset subgroup. Subtyping of T2DM patients can help to identify the high-risk populations of cerebrovascular disease.

Objective:To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) .Methods:From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis.Results:①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five na?ve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions:There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

Malignant tumors have become the main cause of human death.With the prolonged use of chemotherapeutic drugs during the treatment process,tumor cell resistance is also constantly increasing.long non-coding RNA(lncRNA)is an important mem-ber of the non-coding RNA family.Cancer susceptibility candidate 2(CASC2)is a type of long non-coding RNA,high expression of CASC2 can inhibit tumor cell development and reduce drug resistance of tumor cells by promoting apoptosis,regulating signaling path-ways,participating in cellular transmission pathways,competitively binding of miRNA,and changing the protein structure or functional status.This article will provide a comprehensive review of the regulatory effects and mechanism of lncRNA CASC2 on chemotherapy resistance in malignant tumors.

MicroRNAs (miRNAs) are a class of small, single-stranded non-coding RNAs that act as important regulators of gene expression and are involved in a number of important processes in life. A large number of studies have suggested that dysregulation of miRNA expression may be an important part of the mechanism of human tumorigenesis and progression. MiR-155-5p is mainly regarded as an oncomiR that acts on multiple target genes to participate in tumor progression, although it has been suggested to possess cancer growth suppressor effects. In this paper, we summarize the effects of miR-155-5p on cancer cell proliferation, invasion, migration, and drug resistance in various tumor types and elucidate its value as a possible potential marker in assisting diagnosis.

Objective:To explore the risk factors in leukemia transformation (LT) in those with myelodysplastic syndromes (MDS) .Methods:From January 2012 to December 2020,data on 320 patients with newly diagnosed primary MDS were gathered from the MDS center. The clinical features and molecular characteristics are explored. Additionally, a retrospective analysis of risk factors for the development of acute leukemia from MDS was done.Results:The median follow-up was13.6 (0.4-107.3) months. 23.4% (75/320) of the MDS patients had LT group. Significant differences between the LT group and non-LT group can be seen in age ( P<0.001) , bone marrow blast percentage ( P<0.001) , bone marrow fibrosis ( P=0.046) , WHO classification ( P<0.001) , IPSS-R ( P<0.001) and IPSS-R karyotype group ( P=0.001) . The median number of mutation of LT group was 1 (1, 3) , that in non-LT group was 1 (0, 2) ,which had a statistical difference ( P=0.003) .At the time of the initial diagnosis of MDS, the LT group had higher rates of the TP53 mutation ( P=0.034) , DNMT3A mutation ( P=0.026) , NRAS mutation ( P=0.027) and NPM1 mutation ( P=0.017) . Compared with the mutations at first diagnosis and LT of six patients, the number of mutations increased and the variant allele frequencies (VAF) increased significantly in LT patients. Higher bone marrow blast percentage (Refer to <5% , 5% -10% : HR=4.587, 95% CI 2.214 to 9.504, P<0.001, >10% : HR=9.352, 95% CI 4.049 to 21.600, P<0.001) , IPSS-R cytogenetic risk groups ( HR=2.603, 95% CI 1.229-5.511, P=0.012) , DNMT3A mutation ( HR=4.507, 95% CI 1.889-10.753, P=0.001) , and NPM1 mutation ( HR=3.341, 95% CI 1.164-9.591, P=0.025) were all independently associated with LT in MDS patients, according to results of multivariate Cox regression. Conclusion:Bone marrow blast percentage, IPSS-R cytogenetic risk groups, DNMT3A mutation, and NPM1 mutation are independent risk factors in LT for MDS patients.

Objective:Objective The inhibitory effect of Niuhuang Qinggan Capsule on 2019-nCoV virus was studied to provide experimental evidence for drug screening and treatment of 2019-nCoV acute respiratory disease.Methods:The 2019-nCoV virus GS048 strain was isolated and cultured by Vero-E6 cells. The solution of Niuhuang Qinggan capsule was incubated with virus in vitro to determine the change of virus titer. The effect of Niuhuang Qinggan capsule on the proliferation of 2019-nCoV virus was determined by cell culture medium method.Results:It was found that the concentration of 274.3 μg/ml was not toxic to the cells when the concentration of drugs was lower. When the drug was incubated with virus, the titer of virus decreased from 10 4.4TCID 50/ml to 10 2.8TCID 50/ml. In vitro 2019-nCoV virus culture experiment showed that the addition of the drugs reduced the cytopathy, and the logarithmic value of virus titer decreased by 40% -50%. Conclusion:In this study, in vitro inhibition experiments suggest that Niuhuang Qinggan capsule has the potential to inhibit the proliferation of 2019-nCoV. It can be used as a candidate drug to further verify the therapeutic effect of the 2019-nCoV acute respiratory disease.

Objective:To observe the effects of intervention based on self-regulation mode on illness perception, medical coping styles and quality of life of patients with psoriasis.Methods:Eighty patients with psoriasis from February 2018 to August 2019 in Qinhuangdao First Hospital were selected and divided into two groups by random digits table method, 40 patients in each group. The control group was given routine intervention, and the experimental group was given intervention based on self-regulation mode. The Illness Perception Questionnaire-Revised (IPQ-R) scores, Medical Coping Modes Questionnaire (MCMQ) scores, dermatologylifequalityindex (DLQI) scores and compliance of the two groups were compared before and after intervention.Results:There was no significant difference in the score of IPQ-R, MCMQ, DLQI before intervention between the two groups( P>0.05). After intervention, scores of symptoms, disease perception and causes of the disease in IPQ-R were (7.24±0.75), (162.34±20.35), (76.23±8.65) points in the experimental group and (6.08±0.72), (123.26±18.57), (52.79±7.84) points in the control group, there were significant differences between the two groups ( t values were 7.057, 8.972, 12.699, P<0.01). In the MCMQ, facing score,avoidance score and yielding score were (25.67±2.83), (12.26±1.84), (9.12±1.24) points in the experimental group, (21.76±3.89), (14.35±2.48), (10.45±1.68) points in the control group, there were significant differences between the two groups ( t values were 5.141, -4.280, -4.028, P<0.01). The DLQI scores of experimental group were significantly higher than those of control group ( t values were 2.648-8.244, P<0.05 or 0.01), and compliance of experimental group (97.5%, 39/40) was significantly better than control group (80.00%, 32/40) with statistically significant( Z value was 40.000, P<0.01). Conclusions:Intervention based on self-regulation mode can effectively reduce negative emotions of patients with psoriasis, increase their illness perception and compliance, improve their medical coping styles, self-management ability and quality of life, with positive application value.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example,

Enhancer of zeste homolog 2 (EZH2) is a catalytic subunit of polycomb repressive complex 2 (PRC2). It acts as a histone methylation transferase and plays a key role in oncogenesis, development, metastasis, and drug tolerance. Studies have found that the expression of EZH2 is regulated by a variety of carcinogenic transcription factors, anti-cancer microRNA, tumor-related non-coding RNA and post-translational modifications. Moreover, the effect of EZH2 in silencing target genes is mainly through trimethylation of histone H3 at lysine 27 (H3K27me3). This article summarizes the main regulatory roles and functions of EZH2 in tumorigenesis, and reviews the progress of target therapies based on EZH2.

Objective:To evaluate the pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap for the treatment of soft tissue defects at the contrallateral leg.Methods:Between January of 2012 and January of 2016, 8 patients with soft tissue defects at the leg were treated at Department of Orthopedic Surgery, Hand and Foot Surgery Hospital of Lanzhou. They were 5 men and 3 women, aged from 19 to 50 years (mean, 35 years). All of them were treated by bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap pedicled with posterior tibial artery. The size of the defects ranged from 10 cm×9 cm to 13 cm×8 cm. The immediate coverage of the muscle flaps and vessel pedicle was repaired by a meshed split-thickness skin graft. The donor site was closed directly. The therapeutic efficacy was assessed at the final follow-up according to the criteria by Iowa for tibial fractures.Results:All the skin flaps and muscle flaps survived without any vascular crisis. One case developed necrosis of small skin graft at the distal muscle flap which spontaneously healed after dressing change for 2 weeks. Their follow-up ranged from 2.5 to 4.5 years (mean, 3.8 years). A good contour was confirmed at the recipient area. By the Iowa criteria at the final follow-up, 3 cases were excellent, 4 good and one fair.Conclusion:Pedicled bridge transplantation with medial leg skin flap and medial hemi-soleus muscle flap is a good treatment for soft tissue defects at the contrallateral leg which has only one major blood vessel, reducing damage to the donor site.