Major depressive disorder (MDD) has become an increasingly serious public health issue, characterized by high incidence and high disability rates. It often coexists with other mental health problems and physical diseases, with a significant negative impact on patients' quality of life. In clinical practice, MDD is considered a heterogeneous disease. The complexity of the pathological mechanisms and the variability in treatment responses lead to a lack of clear therapeutic targets, which complicates the treatment process. In recent years, with advancements in neuroscience, the crucial role of microglia in the pathogenesis of MDD has been revealed. As the main immune cells in the brain, microglia are not only involved in the regulation of neuroinflammation but also play important roles in neurogenesis and neuronal regulation in MDD. This article mainly discusses the role of microglia in the pathophysiological mechanisms of MDD, aiming to provide a theoretical basis for microglia as a potential target for the treatment of MDD.

ObjectiveTo understand the serotype distribution and drug resistance of salmonella contaminated in commercially available food. MethodsSalmonella detection， including the serotypes， was conducted in food products sold in Pudong New Area from 2020 to 2022. The antimicrobial susceptibility test of 15 antibiotics was conducted by the broth microassay. ResultsA total of 118 salmonella strains were detected in 2 497 pieces of food， with a total detection rate of 4.7%. The dominant detection categories were poultry meat， livestock meat and aquatic products. The 118 salmonella strains could be divided into 24 serotypes， Salmonella enteritidis （26.4%）， Salmonella Typhimurium （16.2%） and Salmonella delpy （14.4%） were the main dominant types. Salmonella had the highest resistance rate to ampicillin （63.6%）， followed by tetracycline， chloramphenicol， cotrimoxazole and nalidixic acid. Among the three dominant serotypes， the multidrug resistance rate of Salmonella typhimurium was the highest （89.5%）， followed by Salmonella delpy （70.6%） and Salmonella enteritidis （61.3%）. ConclusionLivestock， poultry meat， and aquatic products are seriously contaminated by salmonella with diverse serotypes. The livestock meat is mainly contaminated by Salmonella typhimurium and Salmonella delpy， and the poultry meat is mainly contaminated by Salmonella enteritidis. The drug resistance spectrum is wide and the multi-drug resistance rate is high. Different from the livestock and aquatic isolates， poultry meat-derived strains have high tolerance to ampicillin， nalidixic acid and polymyxin， and carry certain potential food safety risks.

Objective:To explore the clinical characteristics and outcomes of pediatric kidney transplantations at a single center and discuss the related clinical issues.Methods:From January 1990 to October 2019, clinical data were analyzed retrospectively for 244 pediatric renal transplants. The youngest recipient was aged 1.8 years and the median age of pediatric recipients was 12.2 years. The major disease was primary or hereditary glomerulonephritis ( n=160, 69.0%), congenital anomalies of kidney and urinary tract (CAKUT), cystic renopathy and other hereditary nephropathies ( n=55, 23.7%). The donor sources included traditional deceased donor ( n=42, 17.2%), living-related donor ( n=19, 7.8%) and organ donation ( n=183, 75.0%). The median age of donors was 2 years (0-51) and the median weight 12.0(2.7-72.0) kg. From January 2013 to October 2019, 170 cases), the major induction immunosuppression regimen was anti-thymocyte globulin (ATG) ( n=110, 64.7%) or basiliximab ( n=58, 34.1%). The maintenance regimen was tacrolimus + mycophenolic acid (MPA) + glucocorticosteroids. Finally the outcomes and the complications were analyzed. Results:The survival rates of 244 kidney allograft recipients were 98.1%, 94.5% and 93.4% and the graft survival rates 92.6%, 84.2% and 82.0% at 1/3/5 years respectively. Ten recipients died of accident ( n=2, 20.0%), pneumonia after transplantation ( n=2, 20.0%) and intracranial hemorrhage ( n=2, 20.0%). Thirty-three recipients lost their allografts mainly due to intravascular thrombosis in graft ( n=5, 14.3%), acute rejection ( n=5, 14.3%) and death ( n=9, 25.7%). Besides, among 109 deceased donor allograft recipients, the postoperative outcomes were delayed graft function recovery (DGF) ( n=27, 24.8%), arterial thrombosis ( n=6, 5.5%), venous thrombosis ( n=1, 0.9%), graft perirenal hematoma ( n=6, 5.5%), raft artery stenosis ( n=10, 9.2%) and graft ureteral fistula ( n=1, 0.9%). The incidence of acute rejection was 17.5% and 23.2% at 1/3 year respectively. The recurrent rate of primary disease was 6.9%, including primary FSGS ( n=3, 42.9%) and IgA nephropathy ( n=2, 28.6%). At 1/3 year post-operation, the incidence of pulmonary infection was 16.9% and 22.4% and the incidence of urinary tract infection 26.9% and 31.7%. Excluding recipients with graft failure, the estimated glomerular filtration rate (eGFR) at 1/2/3 year postoperatively was (80.3±25.2), (81.4±27.8) and (71.8±27.6) ml/(min·1.73 m 2)respectively. Conclusions:The outcomes of pediatric renal transplantations are excellent at our center. Future efforts shall be devoted to optimizing the strategies of donor kidney selection and strengthening preoperative evaluations, perioperative and postoperative managements for improving the long-term outcomes of pediatric renal transplantations.

Objective:To evaluate the safety and efficacy of endovascular interventional treatment of the intracranial vertebrobasilar trunk large aneurysms (VBTLAs) compared with conservative treatment.Methods:This is a prospective multi-center cohort study. From October 2012 to October 2018, a total of 69 patients with intracranial vertebrobasilar trunk large aneurysm (diameter>10 mm) from Henan Province People's Hospital and People's Liberation Army Rocket Medical Center were included in this study. Patients themselves chose either endovascular interventional therapy (interventional group) or conservative treatment (conservative group) after discussion with their doctors. The χ 2 test was used to compare the incidence of deaths, stroke, and all other serious adverse events including other site bleeding, myocardial infarction and others between the two groups. Results:A total of 69 patients were enrolled, of whom 51 patients were enrolled in interventional group, 18 patients underwent endovascular reconstructive therapy, 11 patients underwent deconstructive therapy, and 4 patients underwent conjunction interventional treatments. Eighteen patients were enrolled in conservative group, of whom 11 cases received simple risk factor control, 7 cases received antiplatelet and risk factors control. The proportions of hypertensive patients 94.4% (17/18) and giant aneurysms 50.0% (9/18) in the conservative group were higher than those in the surgery group 64.7% (33/51, χ 2=4.500, P=0.034), 19.6% (10/51, χ 2=4.730, P= 0.030).The incidence of all serious adverse events associated with protocol was 15.7% (8/51) in the interventional group and 44.4% (8/18) in the conservative group [risk ratio (RR) =0.353, 95% confidence intervals (CI): 0.156-0.801], and the difference was significant (χ 2=4.668, P=0.031). The incidence of fatal events associated with protocol was 2.0% (1/51) in the interventional group and 38.9% (7/18) in the conservative group (RR=0.050, 95%CI: 0.007-0.382), and the difference was significant (χ 2=14.281, P<0.001). The incidence of hemorrhage events associated with protocol was 2.0% (1/51) in the interventional group and 22.2% (4/18) in the conservative group (RR=0.088, 95%CI: 0.011-0.738), and the difference was significant (χ 2 =5.391, P=0.020). Follow-up imaging showed that the occlusion rate of aneurysms in 44 patients in the interventional group was 56.8% (25/44) after a median follow-up of 6 months. Imaging follow-up was obtained in 9 patients, whose occlusion rate of aneurysms was 0 and the median follow-up time was 12 months, in the conservative group. The difference was significant(χ 2 =7.534, P=0.006). Conclusion:Compared with conservative treatment, endovascular intervention of the intracranial VBTLAs has lower incidences of serious adverse events and death events.

OBJECTIVE: To explore the application value of rectal prolapse constipation balloon in single auxiliary defecation. METHODS: Forty-one patients with moderate or severe rectocele were treated with a rectocele constipation balloon through the vagina. The defecography and VAS scores were compared before and after implantation. RESULTS: There was a significant difference between the anorectal angle, rectocele, and VAS scores before and after intervention in defecography (<0.01). CONCLUSIONS A single assisted defecation of the rectocelicular constipation balloon is feasible.
Constipation ; diagnosis ; Defecation ; Defecography ; instrumentation ; Female ; Humans ; Rectal Prolapse ; Rectocele

Objective To retrospectively analyze the clinical effect of 131 I in the treatment of hyperthyroid heart disease.Methods 269 cases who received nuclear medicine 131 I therapy for hyperthyroid heart disease were selected.Clinical laboratory and related examinations,including determination of serum thyroid hormones and antibod-ies (FT3 ,FT4 ,TSH,TRAb,TGAb and TPOAb),biochemical indicators,analysis of blood,electrocardiogram,thyroid ultrasonography,thyroid 131 I uptake rate determination,static imaging and color Doppler ultrasound of the heart were condutced.After diagnosis clear integrated touch technique,thyroid color Super and the thyroid static imaging deter-mine thyroid weight.131 I dose by following formula calculation determine:131 I dose =(each grams thyroid plans vol-ume)×thyroid weight (g)/thyroid 24h or highest 131 I rate (%),each grams thyroid plans volume for 2.96-4.44MBq,calculation 131 I dose,application SPSS 17.0 statistics software for statistics,used paired t test to analyze serum hormone levels of FT3 ,FT4 ,sTSH before treatment,3,6 and 12 months after treatment.Results After 131 I treatment 3,6,12 months,serum FT3 ,FT4 ,sTSH levels significantly declined compared with before treatment (t =36.03,23.88,17.81,45.01,24.85,13.95,49.97,25.66,10.28,all P <0.01).Of 269 patients received 131 I treat-ment,hyperthyroidism cured in 220 cases (81.8%),improved in 42 cases (15.6%),invalid in 7 cases (2.6%);hyperthyroidism heart recovered in 226 cases (84.0%),effective rate was 97.0%(261 /269).Conclusion The treatment of hyperthyroid heart disease as soon as possible is the key to control hyperthyroid,reduced thyroid hormone in the peripheral circulation,131I can be fast and effective treatment of hyperthyroidism,hyperthyroid abnormal ECG and cardiac anomalies symptom relief for time is the ideal treatment of hyperthyroid heart disease recovery as soon as possible,with normal thyroid function,hyperthyroid can return to normal or part of normal.

OBJECTIVETo evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using siRNA-loaded nano-scale microbubbles (siRNA-NBs).

METHODSsiRNA-NBs were prepared by hetero-assembly of polymeric siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light scattering. The distributions of cy3-labled siRNA in the tumor tissues were evaluated using confocal laser scanning microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by contrast-enhanced ultrasonography.

RESULTSThe siRNA-NBs had a mean diameter of 400.7 ± 30.5 nm with a weak positive charge of +8.8 ± 0.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of blood supply during gene therapy.

CONCLUSIONSAs a novel ultrasound contrast agent, siRNA-NBs make possible the integration of tumor gene therapy and therapeutic effect evaluation for cancer.

Apoptosis ; Contrast Media ; Gene Silencing ; Genetic Therapy ; Humans ; Liposomes ; Micelles ; Microbubbles ; Neoplasms ; therapy ; Particle Size ; Polymers ; RNA, Small Interfering ; Sirtuin 2 ; genetics ; Ultrasonics

Membrane type-1 matrix metalloproteinase (MT1-MMP or MMP14) plays the pivotal role in tumor development and metastasis, so it is a promising drug target in malignancy. To acquire MT1-MMP specific binding peptides, we first analyzed MMPs sequences to find the divergent and specific sequence of MT1-MMP by bioinformatics approach, then set the specific sequence as the sense peptide target and designed antisense peptide library. Finally, by means of molecular docking, molecular dynamics simulation and in vitro cell assays, we screened the antisense peptide library against MT1-MMP and further studied the obtained specific peptides. Here, we identified the divergent and specific sequence of AYIREGHE (Named MT1-loop) located in MT1-MMP loop by multiple sequence alignment and established the antisense peptides library with capacity of 1 536 sequences. After two rounds of virtual screening, we obtained five antisense peptides with Rerankscores in the top for further screening. They all interacted with MT1-MMP, and docked well at the active site composed of MT1-loop sequence. Analysis of the affinities of these five antisense peptides to other MMPs (MMP1-3, MMP7-13, MMP14 HPX, MMP16) revealed that the peptide FVTFPYIR was more specific to MT1-MMP. Molecular dynamics simulation showed that the peptide FVTFPYIR might affect the stability of MT1-MMP and thus have effects on its activities. Meanwhile, the peptide FVTFPYIR could specifically inhibit the growth of MG63 and MDA-MB-231 tumor cells both of which expressed MT1-MMP. The work provides a new insight and way for the development of antitumor lead peptides targeting MT1-MMP.
Amino Acid Sequence ; Humans ; Matrix Metalloproteinase 14 ; chemistry ; Molecular Dynamics Simulation ; Neoplasms ; Peptide Library ; Peptides ; chemistry

Objective To evaluate the usefulness of free angle M-mode echocardiography (FAM) in obtaining tricuspid annular plane systolic excursion (TAPSE) for assessing the fetal right ventricular function,and to compare the results of measurements of TAPSE by conventional M-mode(CM) and FAM.Methods Two hundred and forty-three normal fetuses in second and late trimester were divided into 5 groups by gestational age(GA):20-24 weeks,24+1-28 weeks,28+1-32 weeks,32+1-36 weeks,36+1-40 weeks.The TAPSE were measured by CM and FAM echocardiography,meanwhile multiple parameters for evaluating right ventricular function were obtained by using myocardial tissue Doppler imaging (TDI),and the correlation between TAPSE and other parameters were analyzed by linear correlation.ANOVA was used to compare CM-TAPSE,FAM-TAPSE,Em,Sm and right ventricular fractional shortening(RVFS)with different GA.Regression equation estimate was used to compare the relationship of FAM-TAPSE with GA.Independent sample t test was used to compare CM TAPSE with FAM TAPSE.Results There were significant differences in CM-TAPSE,FAM-TAPSE,Em,and Sm among 5 groups (P =0.000),the measured value of FAM-TAPSE was higher than that of CM TAPSE (P =0.000).Both FAM-TPASE and CM-TAPSE showed significant positive correlations with GA,Em and Sm,but FAM TAPSE demonstrated better correlation than CM-TAPSE.Conclusions By adjusting sample line of FAM,measuring the maximum displacement of tricuspid annular plane is feasible,and FAM may evaluate fetal right ventricular function more accurately and effectively.

Objective To evaluate the feasibility of integrating cancer gene therapy with therapeutic effect evaluation using siRNA-loaded nano-scale microbubbles (siRNA-NBs). Methods siRNA-NBs were prepared by hetero-assembly of polymeric siRNA micelles and liposomal microbubbles, and the particle sizes and surface potentials were examined with dynamic light scattering. The distributions of cy3- labled siRNA in the tumor tissues were evaluated using confocal laser scanning microscopy. A siRNA targeting the anti-apoptosis gene SIRT2 was designed and its gene silencing effects was tested in vivo using siRNA-NBs with ultrasound exposure. The therapeutic effect of the loaded siRNA-NBs was evaluated by contrast-enhanced ultrasonography. Results The siRNA-NBs had a mean diameter of 400.7 ± 30.5 nm with a weak positive charge of+8.8 ± 0.8 mV. With ultrasound exposure, siRNA-NBs effectively delivered cy3-siRNA into the cytoplasm of cancer cells and caused SIRT2 suppression and cell apoptosis in tumor tissues, resulting in significantly suppressed tumor growth. In addition, contrast-enhanced ultrasonography of siRNA-NBs provided good imaging quality to allow real-time observation of blood supply during gene therapy. Conclusions As a novel ultrasound contrast agent, siRNA-NBs make possible the integration of tumor gene therapy and therapeutic effect evaluation for cancer.