BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.

Objective To study the prognostic factors of progressive hearing loss among children with large vestibular aqueduct syndrome(LVAS).Methods The clinical data of 49 children(95 ears)with LVAS who re-ceived at least two hearing tests from January 2017 to January 2023 in our hospital were retrospectively analyzed,and they were divided into two groups according to the progression of hearing loss:the stable group(55 ears)and the progressive group(40 ears).The effects for progressive hearing loss of initial age,gender,laterality,imaging features,audiometric data,and incomplete partition type Ⅱ(IP-Ⅱ)and SLC26A4(type A,B,C,D)genotypes were analyzed by univariate and multivariate Cox regression analysis.The potential prognostic factors were further verified by Kaplan-Meier survival analysis.Results Each dB decrease in the initial average hearing threshold in-creased the expected hazard by 7.03％(P=0.02).Incomplete partition type Ⅱ(IP-Ⅱ)was associated with 5.11 hazard ratio(95％CI,1.81 to 14.45,P=0.002).Genotype C was associated with 6.13 hazard ratio for progressive hearing loss(95％CI,2.07 to 18.13,P=0.001).Conclusion The initial average hearing threshold,IP-Ⅱ,and SLC26A4 genotype C were significant effect factors of progressive hearing loss in patients with LVAS.This could predict the progression of hearing loss in children with LVAS and help identify patients at high risk for progressive hearing loss.

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

Objective:To compare the tropism of different adeno-associated virus (AAV) serotypes in retinal cells.Methods:The plasmids pFastBacDual-inCap and pFastBacDual-ITR-CMV-EGFP were constructed for AAV packaging with the baculovirus expression system.Recombinant adeno-associated virus type 2(rAAV2), 6, 8 and 9 serotypes were packaged, and the infectivity of rAAV was evaluated by infecting HEK293T cells at multiplicity of infection(MOI)2000.Twenty-five C57BL/6 mice were divided into five groups, with five mice per group.In the three experimental groups, both eyes of each mouse were injected 1 μl rAAV intravitreally, and 1 μl phosphate buffered saline (PBS) for the eyes of the control group.Two weeks after injection, the retinal tissues were collected for preparing flat mounts and cryosections.Enhanced green fluorescent protein (EGFP) gene expression was observed via fluorescence microscopy and laser scanning confocal microscopy.The study protocol was approved by the Ethics Committee of Suzhou Institute of Biomedical Engineering and Technology.Results:The infection efficiency of the recombinant virus to HEK293T cells was rAAV2>rAAV6>rAAV8>rAAV9, and the transduction efficiency was 39.5%, 18.4%, 8.7% and 4.6%, respectively.In mouse retinal transduction, rAAV2 and rAAV6 were highly expressed in the ganglion cells, and rAAV8 and rAAV9 were highly expressed in the retinal pigment epithelium (RPE) and photoreceptor cells.rAAV2-mediated EGFP expression in retinas was stable within three months after injection.Conclusions:Different rAAV serotypes have varying tropism and transduction efficiencies in retinal cells through intravitreal injection, rAAV2 has a high transduction efficiency and it can be stably expressed in retinas within three months after injection.

Objective:To study the impact of repeat hepatectomy for patients with post-hepatectomy recurrent hepatocellular carcinoma (HCC).Methods:The data of patients who developed post-hepatecotmy recurrent HCC and underwent repeat hepatectomy at the General Surgery Department of Beijing Tongren Hospital from May 2013 to May 2016 (the Recurrence Group), were retrospectively compared with the data from patients who underwent initial hepatectomy for HCC during the same study period (the Primary Group). The general data, perioperative data, postoperative complications and survival of the two groups were compared.Results:The primary group included 179 patients, consisting of 133 males and 46 females, aged (57.3±11.7) years, with a range from 14.0 to 84.0 years. The recurrence group included 36 patients, consisting of 30 males and 6 females, aged (55.9±11.4) years, with a range from 40.0 to 77.0 years. There were no statistically significant differences between the two groups in gender, age, hepatitis virus infection status, preoperative alpha fetoprotein, Child-Pugh score and indocyanine green retention rate at 15 min ( P>0.05). However, there were statistically significant differences ( P<0.05) between the two groups in operative time [(244.2±84.3)min vs. (283.4±66.8)min], intraoperative blood loss[(428.5±151.6)ml vs. (756.2±187.4)ml], anatomic or nonanatomic hepatectomy, single tumor or multiple tumors, and maximum tumor diameter[(5.81±2.24)cm vs. (3.69±1.55)cm]. There were no statistically significant differences between the two groups in incidences of tumor capsular invasion, tumor thrombus and degrees of tumor differentiation ( P>0.05). There were no statistically significant differences in surgical complication rates ( P>0.05), and in 1-year and 3-year overall and disease free survival rates between the two groups ( P>0.05). Conclusions:Repeat hepatectomy for recurrent HCC after hepatectomy was safe and effective. Its long-term survival outcomes were similar to first hepatectomy for HCC.

Objective: To detect the expression of non-coding RNA snord105b in gastric cancer (GC) tissues, sera and cell lines, and its correlation with clinicopathological characteristics of patients with GC as well as its effect on the proliferation of GC cells. Methods: One hundred and twenty pairs of GC tissues and corresponding para-cancerous tissues from patients, who underwent surgery at Department of Surgery, the Fourth Hospital of Hebei Medical University between 2016 and 2017, were collected for this study. The presurgical sera samples from GC patients (n=50) and peripheral venous blood samples from healthy donors (n=30), as well as five gastric cancer cell lines (SGC-7901, AGS, MGC-803, BGC-823, HGC-27) and gastric mucosa normal epithelial GES-1 cells were also obtained. qPCR assay was adopted to detect the expression of snord105b in GC tissues, sera and cell lines. The correlation between snord105b and patients’clinicopathological features was investigated. MTS assay was adopted to detect the effect of snord105b silence or over-expressionon in vitro proliferation of four GC cells. Results: qPCR assay demonstrated that the expression of snord105b in GC tissues, sera and cell lines were significantly higher than that of para-cancerous tissues, sera from healthy donors and GES-1 cells (all P< 0.05). Expression level of snord105b was obviously associated with age,tumor size, differentiation and TNM stages of patients (all P<0.05). MTS assay demonstrated that knockdown of snord105b could suppress the proliferation of GC cells (P< 0.05), while forced-expression of snord105b could promote the proliferation of GC cells (P< 0.05). Conclusion: non-coding RNA snord105b aberrantly expressed in GC tissues, sera, and cells, and its expression was obviously correlated with patients’age, tumor size, differentiation and TNM stages. Snord105b could significantly promote the proliferation of GC cells, which may be used as a potential clinical biomaker for early diagnosis and prognosis of GC.

PURPOSE: Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model. RESULTS: The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer. CONCLUSION: These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.
Biomarkers ; Chemoradiotherapy ; Dermatitis ; Diarrhea ; DNA Mismatch Repair ; Follow-Up Studies ; Genetic Variation ; Genotype ; Humans ; Leukopenia ; Logistic Models ; Methods ; Odds Ratio ; Polymorphism, Single Nucleotide ; Prognosis ; Rectal Neoplasms

Objective To evaluate the risk factors for intraoperative hemodynamic instability (HI) in patients with adrenal incident pheochromocytoma.Methods Perioperative clinical parameters of patients undergoing surgery for adrenal incident pheochromocytoma at the First Hospital of Peking University from January 2001 to July 2018 were analyzed.There were 39 males and 41 females,with mean age of 45.1 years (13-76 years old).The median tumor length was 5.1 cm (1.5-14.0 cm),with 25 cases (31.3％) on the left side,55 cases (68.8％) on the right side.There were 37 cases combined with coronary heart disease or diabetes or BMI≥24 kg/m2.Patients were divided into hemodynamic instability (HI group) and hemodynamic stability group (HS group) by whether intraoperative hemodynamic instability occurred.The differences of demographic characteristics and clinical parameters between the two groups were compared.Logistic regression analysis was done for seeking the risk factors for hemodynamic instability during surgery.Results There were 54 cases (67.5％) in the HS group and 26 cases (32.5％) in the HI group.Univariate analysis showed that there was no significant difference in age [(44.06 ± 13.58) years old vs.(47.35 ± 16.11) years old],combined with coronary heart disease or diabetes or BMI≥24 kg/m2 [50.0％(27/54) vs.38.5％ (10/26)],tumor long diameter [median 5.0 cm(1.5-14.0 cm) vs.6.0cm(1.5-13.5 cm)],tumor location [left:29.6％ (16/54) vs.34.6％ (9/26)],preoperative catecholamine test positive [44.4％ (20/45) vs.50.0％ (10/20)],open surgery [27.8％ (15/54) vs.34.6％ (9/26)]and preoperative non-alpha blockers[13.0％ (7/54) vs.30.8％ (8/26)] between HS group and HI group (P ＞ 0.05).Further logistic regression analysis was used to analyze the risk factors of intraoperative hemodynamic instability.Multivariate analysis found that patients who preoperative non-alpha blockers before surgery were independent risk factor for HI (OR =4.574,95 ％ CI 1.273-16.432,P =0.020).Conclusions Preoperative non-alpha blocker in patients with adrenal incidental pheochromocytoma could be independent risk factor for intraoperative hemodynamic instability.Therefore,it is recommended that patients with adrenal incidental tumors,especially those who fail to rule out pheochromocytoma,take preoperative alpha blockers.

Objective: To establish the domestic matrix assisted laser desorption/ionisation time of flight mass spectrometry database for identification of clinical mycobacteria and evaluate its accuracy with foreign counterpart. Methods: The establishment of "Chinese Pathogenic Mycobacteria Mass Spectrometry Database" : nineteen American type culture collection strains from 19 species and 183 "standardized" isolates from 42 species were selected and extracted by modified ultrasonic extraction method for spectral acquisition and database establishment based on microTyper MS. Each extract was dropped onto 12 spots and tested twice to generate 24 spectrum, then at least 20 qualified spectrum according to the standard were selected. Subsequently they were composed into one main spectra (MSP) by setting peak number maximum, peak frequency minimum and mass tolerance. Verification of database: Totally 305 mycobacteria from different regions were used for comparison of accuracy and spectral features between microTyper MS based on domestic database and imported MALDI TOF MS base on Mycobacteria Library 3.0 database. Results: The database composed of 202 stains from 42 species was constructed, with an average of 4.8 in each species. The top ten were M. Kansasii(16), M. intracellulare(16), M. gordonae(16), M. fortuitum(16), M. avium(16), M. abscessus(16), M. tuberculosis(15), M. marseillense(11), M. arupense(10), M. yongongens(8). A total of 305 isolates were confirmed belonging to 22 species by sequencing. The accuracy based on this database was 99.67% (304/305), which was better than the Mycobacteria Library 3.0 database (χ²=4.06, P<0.05). Conclusion The construction of the "Chinese Pathogenic Mycobacteria Mass Spectrometry Database" meets the requirement of routine clinical application and was more accurate than its counterpart in terms of domestic comment strains.(Chin J Lab Med, 2018, 41: 519-526)

Objective To explore the risks and its influencing factors of patients with psychotic disorders in communities.Methods A total of 457 patients with psychotic disorders in communities were investigated by use of the multistage stratified cluster random sampling method.Results Totally 257 patients with psychotic disorders in communities were with risks,which accounted for 56.2％.Among them,200 patients (43.8％) were with level-0 risk,113 patients (24.7％) were level-1 risk,85 patients (18.6％) were level-2 risk,43 patients (9.4％) were level-3 risk,11 patients (2.4％) were level-4 risk,while 5 patients (1.1％) were level-5 risk.There were significant differences in risks among patients with different gender,family income,duration,type of disease,medication and the history of violent behavior.Logistic regression analysis showed that low family income (OR=0.515,95％ CI=0.386-0.689,P＜0.01),long course of disease (OR=1.378,95％CI=1.179-1.609,P＜0.01),patients with schizophrenia (OR=6.285,95％CI=2.456-16.086,P＜ 0.01) and patients with a history of violence history (OR=28.988,95％CI=10.692-78.592,P＜0.01) were the risk factors of the influencing of patients with psychotic disorders in communities.Conclusions Low family income,long course of disease,patients with schizophrenia and a history of violence history are the influencing factors of patients with psychotic disorders in communities,and the management of follow-up and the strength of supervision among these patients should be reinforced.