High heterogeneity of bone and soft tissue sarcomas limits the development of molecular-targeted therapy but in turn provides an important clue to inner genomic and regulomic diversityof driver pathways that define molecular subtypes associated with patient outcome. The importance of malignant biological behaviorshave been re-emphasized, since tumor arises from the collaborative interplay of oncogenic events acquired the tissue-specifying gene expression programs to survive cancer cells and benefit multi-step tumorigenesis and neoplastic progression. Differ from most epithelial carcinomas that harbor clinically operative mutation sites, sarcomas are characterizedpredominantly by chromosomal alterations and copy-number changes, with low mutation loads. Sarcoma-specific fusion proteins produced by chromosomal translocations are common significant transcription factors, driving tumor cells exhibit an absolute dependence on "transcription addiction". It has been confirmed that cyclin-dependent kinase-7 (CDK7) plays a key role in transcriptional regulation such as cell growth and proliferation, invasion and metastasis. The dysregulated transcriptional regulation acquired during tumor development strictly depends on the essential regulation of CDK7. Targeted inhibition of CDK7 is an effective strategy to suppress tumors, especially those with specific genomic backgrounds (oncogene or fusion-gene driven) which are highly sensitive to CDK7 intervention. Emerging studies have shown that CDK7 is closely related to the malignant behaviors of bone and soft tissue sarcomas, and is expected to become a potential target for the treatment of sarcoma.

Objective:To analyze the incidence of gallstone formation after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) by meta-analysis.Methods:English terms for this meta-analysis included "bariatric surgery, gastric bypass, Roux-n-Y gastric bypass, RYGB, sleeve gastrectomy, SG, cholelithiasis, cholecystectomy, gallstone". Researched articles in Pubmed, Medline and Embase databases were searched up to February 2023 and retrieved for further analysis. The quality of each article was evaluated with Newcastle-Ottawa Scale (NOS). Generated data were analyzed with Revman 5.4.Results:Nine relevant cohort studies were retrieved for this meta-analysis, including a total of 24 255 RYGB patients and 4 500 SG patients. All articles met the requirements after the quality evaluation of NOS. The meta-analysis results showed that the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P<0.001). In subgroup analysis, by administering ursodeoxycholic acid (UDCA) for gallstone prevention, the incidence had no difference between the two groups ( P=0.090), while in the study without UDCA, the incidence of gallstones after RYGB was higher than SG ( P=0.005). In the studies with follow-up time no more than 24 months, the incidence of postoperative gallstones in RYGB group was higher than that in SG group ( P=0.050), but there was no statistical difference when following-up beyond 24 months ( P=0.240). Conclusions:Within 2 years after surgery, RYGB patients have more chances to develop gallstones than SG patients. However, beyond 2-year follow-up, there is no difference between the two procedures. Prophylactical utilization of UDCA after RYGB can effectively reduce the incidence of gallstone formation.

Objective: To investigate the effects of thrombopoietin (TPO) on proliferation and collagen synthesis in pulmonary fibro-blasts induced by TGFβ1. Methods: Cultured human embryonic lung fibroblasts (HFLs) were treated with recombinant human TGF-β1 to induce myofibroblast differentiation. Different concentrations of recombinant human TPO were applied individually or in combina-tion. Cell proliferation rate was determined using the CCK8 assay. Q-PCR and immunofluorescence assay were employed to examine the mRNA and protein expression of α-smooth muscle actin (αSMA) and type I collagen (COL1)A2. Results: TGFβ1 treatment induced HFL transdifferentiation to myofibroblasts was determined by the expression of αSMA, a myofibroblast-specific marker. Cell prolifera-tion increased during the induction. COL1 gene and protein expression were upregulated by TGFβ1 induction (P<0.05). The TGFβ1-in-duced mRNA and protein expression of αSMA and COL1A2 was decreased by TPO treatment (P<0.05), as determined by reverse tran-scription quantitative polymerase chain reaction and immunofluorescence analysis, respectively. The inhibitory rate showed a dose de-pendent effect within a certain TPO concentration range. The CCK8 assay demonstrated that TPO downregulated the TGFβ1-induced proliferation (P<0.05). Furthermore, the expression of heme oxygenase-1 (HO-1) was downregulated in TGFβ1-induced lung fibro-blasts, and these effects were attenuated by TPO administration (P<0.05). Conclusions: TPO can inhibit the TGFβ1-induced prolifera-tion and differentiation of human lung fibroblasts. These effects may be mediated in part by HO-1-related signaling pathways.

Objective:To investigate the changes of cardiac morphology and function in obese patients after bariatric surgery.Methods:The clinical data of 100 patients who underwent bariatric surgery, including gastric sleeve resection and gastric bypass in Beijing Friendship Hospital, Capital Medical University from January 2018 to December 2021 were selected for retrospective analysis, including 67 females and 33 males, aged from 18 to 65 years, with average of (36.7±9.5) years. The software of SPSS 26.0 was used to conduct data analysis. Univariate and Logistic regression analysis was performed on the indicators of patients before bariatric surgery and 1 year after surgery, and ROC curves were drawn to determine the changes of cardiac morphology and cardiac function after bariatric surgery.Results:Compared with preoperative, one year after bariatric surgery, patients′ body weight [(112.2±30.2) kg vs(80.7±23) kg, P<0.001] and body mass indes [(38.77±8.26) kg/m 2vs (27.98±6.54) kg/m 2, P<0.001] were significantly decreased, and systolic and diastolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, blood uric acid, and resting heart rate were also significantly decreased ( P<0.05), cardiac ejection fraction was significantly improved [(65.5±5.9)% vs (67.9±4.7)%, P<0.001], ventricular septum, left ventricular posterior wall, left atrial diameter, left ventricular systolic and end-diastolic diameter were significantly reduced ( P<0.05), while the inner diameter of the ascending aorta was not significantly changed [(3.14±0.39) cm vs (3.09±0.38) cm, P=0.125]. In addition, there were no significant differences in cardiac morphology between gastric bypass and gastric sleeve resection. Logistic regression analysis showed that pre-bariatric BMI value, postoperative BMI reduction value, whether suffering from hypertension, and whether the inner diameter of the ascending aorta was widened were the important influencing factors for the improvement of ejection fraction after bariatric surgery ( P<0.05). The area under the ROC curve for predicting the improvement of ejection fraction was 0.772 (95% CI: 0.669-0.875), the specificity was 85%, the sensitivity was 66%, and the best cut-off point was 0.545. Conclusions:One year after bariatric surgery in obese patients, cardiac ejection fraction was significantly improved, and ventricular septum, left ventricular posterior wall, left atrial diameter, left ventricular systolic and end-diastolic diameter were significantly reduced compared with those before surgery. There was no significant difference between gastric sleeve resection and gastric bypass in the improvement of cardiac function and the effect on cardiac morphology. The combined prediction model composed of preoperative body mass index value, decreased body mass index value at 1 year after operation, whether suffering from hypertension, whether the inner diameter of the ascending aorta is widened and other indicators has a good predictive value for the improvement of ejection fraction in bariatric patients at 1 year after operation.

Objective:To systematically evaluate the effect of bariatric and metabolic surgery on bone metabolism in obese patients.Methods:Search terms for the present meta-analysis included "bariatric surgery, metabolic surgery, sleeve gastrectomy, gastric bypass, bone metabolic indicators, bone mineral density", both in English and corresponding Chinese. PubMed, WOS, Cochrane, CNKI, and VIP databases were searched for longitudinal studies from the establishment of the database to September 20, 2022. The data on bone mineral density and bone metabolic markers in obese patients before and after bariatric surgery were extracted. RevMan5.4 and Stata17.0 software were used for Meta-analysis.Results:A total of 8 clinical studies with 420 patients were included. The results of the meta-analysis showed that compared with the preoperative baseline, lumbar spine bone mineral density ( WMD=0.05, 95% CI: -0.00~0.1), femoral neck bone mineral density( WMD=0.10, 95% CI: 0.05-0.15), hip bone mineral density( WMD=0.14, 95% CI: 0.10-0.17), and serum vitamin D 3 ( WMD=-4.87, 95% CI: -6.34--3.40)were decreased, while parathyroid hormone ( WMD=10.04, 95% CI: 5.32-14.76) was elevated after surgery. Conclusions:Current evidence demonstrates that metabolic and bariatric surgery can lead to decreased bone mineral density and impairs in bone metabolic markers early after surgery. Roux-en-Y gastric bypass surgery cause more adverse effects on bone metabolism than sleeve gastrectomy. The results imply that all patients undergoing metabolic and bariatric surgery should be monitored for bone metabolism and routinely take vitamin D and calcium supplements.

Objective:To investigate and analyze the epidemiological and clinical characteristics of 46 patients with corona virus disease 2019 (COVID-19) in Beijing City.Methods:A retrospective study was conducted to analyze the data of 46 patients with COVID-19 in Beijing from 20th January 2020 to 8th February 2020 at the Fifth Medical Center of the PLA General Hospital in Beijing City. Twelve, 23 and 11 patients were assigned to the mild group, common group and severe group, respectively. The epidemiological history, clinical characteristics, laboratory tests and imaging inspections were analyzed. Statistical analysis used Fisher exact test. If P<0.05, post- hoc test was used for pairwise comparison, and the statistics were corrected by Bonferroni test. Results:Among the 46 patients included in this study, 27 were male and 19 were female. The age range was between 3-79 years old, and the age was (41.8±16.3) years old. The average incubation period was (4.85±3.00) days. A total of 26 cases (56.5%) were clustered patients, and 26 cases had a history of staying in Wuhan, 10 cases had contact with Wuhan personnel. Fever (39 cases, 84.8%), cough (27 cases, 58.7%), and fatigue (25 cases, 54.3%) were the main clinical symptoms for these patients. The decrease in white blood cell counts occurred in 12 patients, four had the decrease in T lymphocyte percentage, 17 had the decrease in CD4 + T lymphocyte counts, seven had the decrease in CD8 + T lymphocyte counts, 21 had the increase level of C reactive protein (45.7%), and interleukin-6 (IL-6) level increased in 32 cases (69.6%), erythrocyte sedimentation rate (ESR) increased in 23 cases (50.0%), serum ferritin level increased in 26 cases (56.5%), and blood lactic acid level increased in nine cases. There were statistically significant differences in the proportion of cases with decreased absolute value of CD8 + T lymphocytes and T lymphocytes counts among the mild, common and severe groups (all P<0.05). Comparing the proportion of cases in the three groups with elevated C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels, the differences were statistically significant (all P<0.05). The proportion of cases with elevated C reactive protein levels in severe group was higher than those in mild and common groups. The proportion of cases with elevated IL-6, ESR, and serum ferritin levels in severe and common group were higher than those in mild group. The proportion of cases with elevated blood lactic acid levels in severe group was higher than those in mild group. The differences between the above groups were statistically significant (all adjusted P<0.017). Analysis of chest X-rays results showed that 34 patients (73.9%) had inflammation in the lungs. Conclusions:The epidemiological characteristics of patients with COVID-19 in Beijing City are mainly imported cases and clustered cases. The clinical manifestations are mainly fever, fatigue and cough. C reactive protein, IL-6, ESR, serum ferritin and blood lactic acid levels are higher in severe patients.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

The oral microbial community is widely regarded as a latent reservoir of antibiotic resistance genes. This study assessed the molecular epidemiology, susceptibility profile, and resistance mechanisms of 35 methicillin-resistant Staphylococcus epidermidis (MRSE) strains isolated from the dental plaque of a healthy human population. Broth microdilution minimum inhibitory concentrations (MICs) revealed that all the isolates were nonsusceptible to oxacillin and penicillin G. Most of them were also resistant to trimethoprim (65.7%) and erythromycin (54.3%). The resistance to multiple antibiotics was found to be largely due to the acquisition of plasmid-borne genes. The mecA and dfrA genes were found in all the isolates, mostly dfrG (80%), aacA-aphD (20%), aadD (28.6%), aphA3 (22.9%), msrA (5.7%), and the ermC gene (14.3%). Classical mutational mechanisms found in these isolates were mainly efflux pumps such as qacA (31.4%), qacC (25.7%), tetK (17.1%), and norA (8.6%). Multilocus sequence type analysis revealed that sequence type 59 (ST59) strains comprised 71.43% of the typed isolates, and the eBURST algorithm clustered STs into the clonal complex 2-II(CC2-II). The staphyloccoccal cassette chromosome mec (SCCmec) type results showed that 25 (71.43%) were assigned to type IV. Moreover, 88.66% of the isolates were found to harbor six or more biofilm-associated genes. The aap, atlE, embp, sdrF, and IS256 genes were detected in all 35 isolates. This research demonstrates that biofilm-positive multiple-antibiotic-resistant ST59-SCCmec IV S. epidermidis strains exist in the dental plaque of healthy people and may be a potential risk for the transmission of antibiotic resistance.
Anti-Bacterial Agents ; therapeutic use ; Dental Plaque ; microbiology ; Female ; Humans ; Methicillin ; Methicillin-Resistant Staphylococcus aureus ; isolation & purification ; Staphylococcal Infections ; diagnosis ; Staphylococcus epidermidis ; isolation & purification

Metastasis accounts for 90% of breast cancer deaths, where the lethality could be attributed to the poor drug accumulation at the metastatic loci. The tolerance to chemotherapy induced by breast cancer stem cells (BCSCs) and their particular redox microenvironment further aggravate the therapeutic dilemma. To be specific, therapy-resistant BCSCs can differentiate into heterogeneous tumor cells constantly, and simultaneously dynamic maintenance of redox homeostasis promote tumor cells to retro-differentiate into stem-like state in response to cytotoxic chemotherapy. Herein, we develop a specifically-designed biomimic platform employing neutrophil membrane as shell to inherit a neutrophil-like tumor-targeting capability, and anchored chemotherapeutic and BCSCs-differentiating reagents with nitroimidazole (NI) to yield two hypoxia-responsive prodrugs, which could be encapsulated into a polymeric nitroimidazole core. The platform can actively target the lung metastasis sites of triple negative breast cancer (TNBC), and release the escorted drugs upon being triggered by the hypoxia microenvironment. During the responsiveness, the differentiating agent could promote transferring BCSCs into non-BCSCs, and simultaneously the nitroimidazole moieties conjugated on the polymer and prodrugs could modulate the tumor microenvironment by depleting nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) and amplifying intracellular oxidative stress to prevent tumor cells retro-differentiation into BCSCs. In combination, the BCSCs differentiation and tumor microenvironment modulation synergistically could enhance the chemotherapeutic cytotoxicity, and remarkably suppress tumor growth and lung metastasis. Hopefully, this work can provide a new insight in to comprehensively treat TNBC and lung metastasis using a versatile platform.