[Construction of a risk prediction model for diabetes after kidney transplantation based on genome-wide association study].

Objective: To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation (PTDM) and construct a risk prediction model for PTDM. Methods: The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital, Ningbo University and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed. The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM. The differences in clinical indicators between the two groups were compared, the risk factors affecting the incidence of PTDM were determined, and susceptibility genes of PTDM were screened by genome-wide association study (GWAS). PTDM risk prediction models based only on clinical indicators (Model 1) and clinical indicators combined with susceptibility genes (Model 2) were established respectively, and the predictive performance of the two prediction models was compared. Finally, the Nomogram of the optimal model was drawn, and the discrimination, calibration and clinical applicability of the model were evaluated. Results: A total of 113 kidney transplant recipients (70 males and 43 females) were included, with an average age of (46.2±10.8) years. There were 51 cases in PTDM group and 62 cases in Non-PTDM group. The related factors screened by GWAS and logistic regression analysis included family history of diabetes (OR=88.912, 95%CI: 5.827-1 356.601, P=0.001), preoperative triglyceride (TG) (OR=1.888, 95 %CI: 1.150-3.098, P=0.012), uric acid (UA) (OR=1.011, 95%CI: 1.000-1.022, P=0.045) and rs802707 (OR=10.046, 95%CI: 1.462-69.042, P=0.019). The area under the curve (AUC) of the receiver operating characteristics analysis (ROC) predicted by Model 1 for PTDM was 0.891 (95%CI: 0.811-0.972), with the sensitivity of 0.889 and the specificity of 0.742. The AUC of ROC curve predicted by Model 2 for PTDM was 0.930 (95%CI: 0.864-0.995), with the sensitivity of 0.885 and the specificity of 0.900. Conclusions: Family history of diabetes, preoperative TG and UA, and rs802707 are significantly associated with the occurrence of PTDM. In addition, the combination of susceptibility genes could improve the predictive ability of clinical indicators for the risk of PTDM.

[Research progress on neurodevelopmental outcomes of small for gestational age infants].

The incidence of perinatal disease and perinatal mortality in small for gestational age infants increased significantly. This group of people is prone to a variety of long-term metabolic diseases and cardiovascular diseases, and is also prone to growth retardation and neurodevelopmental delay, which will seriously affect the long-term quality of life of children. The article studies the neurodevelopmental outcomes of small-for-gestational-age infants. By reviewing and sorting out previous literature, the neurodevelopmental disorders of small-for-gestational-age infants are analyzed according to five aspects: intellectual development, motor development, language development, sensory development, and mental illness. The classification and summary were carried out, and the influencing factors of neurodevelopmental disorders of SGA were also evaluated, so as to provide reference for promoting the improvement of neurodevelopmental outcomes of small-for-gestational-age infants.

[Study of the predictive role of serum HBV RNA on HBeAg serological conversion in children with chronic hepatitis B].

Objective: To investigate the role of serum hepatitis B virus RNA (HBV RNA) in predicting HBeAg serological conversion in children with chronic hepatitis B. Methods: 175 children aged 1~17 years with chronic hepatitis B who received interferon α (IFNα) for 48 weeks were selected. Patients were divided into HBeAg seroconversion and non-conversion based on whether HBeAg seroconversion occurred at 48 weeks of treatment.T-test and Mann-Whitney U test were used to compare between groups; chisquare test or Fisher exact probability method was used to compare the frequency between groups of classified variables; and Pearson correlation was used to analyze the correlation between indicators. Univariate and multivariate logistic regression analyses were used to identify influencing factors associated with HBeAg serological conversion. The predictive effect of HBV RNA, HBV DNA, and HBsAg on HBeAg serological conversion was compared and analyzed by the receiver operating characteristic curve (ROC). Results: The seroconversion rate of HBeAg at 48 weeks was 36.0% (63/175). The reduction in HBVRNA levels from baseline to the 12th, 24th, 36th, and 48th weeks of antiviral therapy was significantly greater in the HBeAg serological conversion group than that in the non-conversion group, and the difference was statistically significant between the two groups (P < 0.05). Univariate and multivariate regression analyses showed that age and a decline in HBV RNA levels at week 12 were independent predictors of HBeAg serological conversion. The area under the ROC curve (AUROC) of HBV RNA decline at week 12 was 0.677(95% CI∶0.549-0.806, P = 0.012), which was significantly better than the same period of AUROC of HBV DNA (0.657, 95% CI∶0.527-0.788, P = 0.025) and HBsAg (0.660, 95% CI∶0.526-0.795, P = 0.023) decline. HBV RNA levels decreased (>1.385 log10 copies/ml) at week 12, with a positive predictive value of 53.2%, a negative predictive value of 72.2%, a sensitivity of 77.4%, and a specificity of 57.9% for HBeAg seroconversion. Conclusion: HBV RNA level lowering during the 12th week of antiviral therapy can serve as an early predictor marker for HBeAg serological conversion in children with chronic hepatitis B.

[Association between sleep duration and activity of daily living in the elderly aged 65 years and older in China].

Objective: To investigate the association between sleep duration and activity of daily living (ADL) in the elderly aged 65 years and older in China. Methods: A total of 11 247 subjects aged 65 and above were included in the Chinese Elderly Health Factors Tracking Survey from March 29, 2005 to April 8, 2019. Self-made questionnaire was used to collect the data of population sociological characteristics, health status and disease status. ADL status was assessed by basic activities of daily living. The association between sleep duration and ADL impairment was assessed by Cox proportional risk regression model. The dose-response relationship between sleep duration and ADL impairment was analyzed using restricted cubic spline function. Results: The age of the subjects was (79±10) years, including 5 793(51.5%) females. The incidence of ADL impairment was 33.3% (3 747/11 247). Subjects were divided into short, medium, and long sleep groups according to sleep duration of fewer than seven hours, seven to eight hours, or more than eight hours. The number of short, medium and long sleepers was 2 974 (26.4%), 4 922 (43.8%) and 3 351(29.8%), respectively. The intermediate sleep group had the lowest incidence of impaired ADL (4.98/100 person-years). Cox proportional risk regression model analysis showed that: taking the intermediate sleep group as reference, after adjustment of gender, age, marital status, educational level, place of residence, living with family, smoking, drinking, exercise, frequency of fruit consumption, vegetable intake frequency, sleep quality, factors such as hypertension, diabetes, heart disease and cerebrovascular disease, the long sleep time increased the risk of impaired ADL [HR (95%CI): 1.148 (1.062-1.241)]. Subgroup analysis showed a weak positive multiplicative interaction between sleep duration and age [HR (95%CI): 1.004 (1.000-1.009)], but no multiplicative interaction between sleep duration and sex [HR(95%CI): 0.948 (0.870-1.034)]. Longer sleep duration increased the risk of ADL impairment in women [HR (95%CI): 1.195 (1.074-1.329)], but not in men [HR (95%CI): 1.084 (0.966-1.217)]. Longer sleep duration increased the risk of ADL impairment in people aged 80 years and older [HR (95%CI): 1.185 (1.076-1.305)], but not in people younger than 80 years [HR (95%CI): 1.020 (0.890-1.169)]. There was a non-linear dose-response relationship between sleep duration and ADL damage (P=0.007), and the risk of ADL damage was lowest when sleep duration was 7.5 h. Conclusion: Sleep duration was positively correlated with the risk of ADL impairment in the elderly in a nonlinear dose-response relationship.

[Construction of zebrafish models for screening intracranial hemorrhage associated genes].

Objective: To construct zebrafish models for the screening of intracranial hemorrhage (ICH) associated genes. Methods: ICH zebrafish models were constructed through morpholino oligonucleotides (MOs) technique and microinjection technique, and multiple verification was performed from macro and micro perspectives. First, the normal wild-type AB strain zebrafish injected with control MO was used as the control group, and AB zebrafish embryos microinjected with MOs of genes related to development of neural crest-derived cells (NCDCs) were used as the study group, such as col8a1 MO, tfap2α MO, msx1a MO, msx2 MO, and dkk1a MO. Preliminary verification of the model was conducted under a white-light optical microscope. Then, the model was verified by Tg (flk1: gfp; gata1: dsRed) double transgenic zebrafish, with vascular endothelial cells labeled by green fluorescent protein (GFP) and red blood cell labeled by fluorescent protein (dsRed), and thus the location of cerebral hemorrhage can be observed more clearly. Specifically, zebrafish embryos were microinjected with Control MO as the control group and those microinjected with col8a1 MO as the study group. Then the embryos were cultured until 48 hours post-fertilization to observe the leakage of red blood cells under the confocal laser scanning microscope. Finally, Tg (flk1: gfp) transgenic zebrafish was used to verify the model based on the blood-brain barrier (BBB). Through the leakage of dextran-rhodamine and DAPI dyes, the destruction of BBB and the occurrence of cerebral hemorrhage in zebrafish were further clarified, and quantitative statistics were carried out to verify the relationship between NCDCs development related genes and cerebral hemorrhage phenotype, which proved that the modeling was effective. Results: The zebrafish with col8a1, tfap2α, and msx1 mutations in the study group had apparent ICH compared with wildtype zebrafish, and the prevalence of ICH was 18.18% (52/286), 23.04% (62/251), and 35.94% (23/64), respectively. While, the zebrafish with msx2 and dkk1a mutations rarely had ICH, with the ICH prevalence of 1.03% (1/97) and 1.15% (1/87), respectively. The prevalence of red blood cells leakage in Tg (flk1:gfp; gata1:dsred) double transgenic zebrafish injected with Control Mo and col8a1 Mo was 0.37% (1/273) and 18.18% (52/286) (P<0.001). The number of DAPI positive nuclei of Tg (flk1: gfp) transgenic zebrafish injected with Control Mo and col8a1 Mo was 10.05±5.27 and 60.35±3.96 (P<0.001), and the fluorescent intensity of midbrain parenchymal induced by dextran-rhodamin leakage was 2.54±4.70 and 5.13±3.52 (P<0.001). Conclusion: This study successfully constructs the ICH zebrafish models, and ICH-related genes are screened out, such as col8a1, tfap2α, msx1, and so on.

[Effects of typical PKC subtypes on the proliferation of mouse pulmonary artery smooth muscle cells and the expression of ERK1/2 and Akt induced by hypoxia].

Objective: To study the effects of specific isoforms of classic protein kinase C (cPKCs) on hypoxia-induced proliferation and the expression of ERK1/2 and Akt using drug intervention or virus transfection in vitro. Methods: Dynal MPC-1 magnetic particle concentrator was used to separate iron-containing pulmonary arterioles fragments, and the pulmonary artery smooth muscle cells (PASMCs) were primary cultured and identified. The cells were intervened by PKC agonist (PMA), PKCα inhibitor (safingol), PKCßⅠ inhibitor (Go6976) and PKCßⅡ inhibitor (LY333531) respectively, and the changes in protein expressions of cPKCs, and the phosphorylation levels of ERK1/2 and Akt were observed by immunoblotting under the condition of normal oxygen or hypoxia. The lentiviral vectors of PKCα and PKCß were used to specifically knock-down the activity of target genes by virus transfection techniques, and Western blotting was used to observe the protein expressions of cPKCs, and the phosphorylation levels of ERK1/2 and Akt in hypoxia-induced PASMCs in mice. Results: With Brdu method, the proliferation of PASMCs induced by hypoxia was significantly inhibited by safingol, Go6976 and LY333531 by inhibiting cPKCα, ßⅠ and ßⅡ respectively. Compared with the hypoxic control group, the rates of Brdu positive cells were (7.35±0.26)% vs (11.28±0.43)%, (3.76±0.25)% vs (7.98±0.28)% and (4.12±0.46)% vs (7.78±0.53)%. We also observed that PMA could significantly promote the proliferation of PASMCs under normoxic condition. Compared with the normoxia control group, the Brdu-positive cell rates were (9.65±0.47)% vs (6.34±0.52)%, (9.34±0.38)% vs (5.42±0.21)% and (7.78±0.53)% vs (4.12±0.46)%. In addition, after transfection with PKCα or PKCß lentiviral vector, the proliferation of PASMCs was significantly lower in hypoxia transfection group than in the control group. The rates of Brdu positive cells were (3.58±0.54)% vs (5.97±0.63)%, respectively. Using Western blotting, we also observed that after being inhibited by safingol, Go6976 and LY333531 respectively, the phosphorylation levels of ERK1/2 and Akt in PASMCs induced by hypoxia was significantly lower than the control group. After using safingol, the phosphorylation levels of ERK1/2 and Akt were (0.56±0.07) vs (1.08±0.13) and (0.49±0.04) vs (0.97±0.08). After using Go6976, the phosphorylation levels of ERK1/2 and Akt were (0.41±0.09) vs (0.79±0.10) and (0.48±0.09) vs (0.82±0.16), after using LY333531, the phosphorylation levels of ERK1/2 and Akt were (0.42±0.03) vs (0.87±0.06) and (0.34±0.07) vs (0.78±0.05). While PMA could promote the phosphorylation levels of ERK1/2 and Akt under normoxic condition, 1.25±0.12 vs 0.41±0.07 and 0.98±0.06 vs 0.37±0.08, respectively. Using transfection technique to specifically knock down the expression of cPKCα and ß, we found that under hypoxic conditions, transfection of PASMCs could significantly lower the phosphorylation levels of ERK1/2, its phosphorylation level was 0.29±0.06 vs 0.76±0.05, with no evident change in the phosphorylation levels of Akt. Conclusions: Hypoxia may lead to phosphorylation of ERK1/2 by promoting the protein expression of cPKCα, cPKCßⅠ and cPKCßⅡ respectively, which eventually induces abnormal proliferation of PASMCs from the distal pulmonary arteries, participating in the development of hypoxic pulmonary hypertension (HPH) of the mice. Regulation of the expression of cPKCα, cPKCßⅠ and cPKCßⅡ may help to attenuate the formation of pulmonary vascular remodeling. Target therapy based on cPKCs is expected to be a new direction for HPH therapy in the future.

[Prognostic analysis of different comprehensive treatment models for locally advanced esophageal squamous cell carcinoma based on propensity score matching].

Objective: To compare the effects of preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the long-term survival of patients with radical resection for esophageal squamous cell carcinoma. Methods: Totally 1 082 patients with stage T3-4aN0-3M0 thoracic esophageal squamous cell carcinoma were recruited in this study who underwent radical resection at Department of Thoracic Surgery, Fourth Hospital, Hebei Medical University from January 2005 to January 2015. There were 798 males and 284 females, with a median age of 61 years (range: 37 to 86 years). There were 138 patients undergoing preoperative neoadjuvant chemotherapy, 392 patients postoperative adjuvant chemotherapy, and 552 patients surgery alone. The neoadjuvant chemotherapy group was used as the benchmark group to match the propensity score with the adjuvant chemotherapy group and the surgery-only group respectively at a ratio of 1∶3. A total of 7 covariates including tumor location, number of positive lymph nodes, tumor invasion depth, tumor differentiation degree, surgical procedure, vascular tumor thrombus and nerve invasion were included, and the caliper value was taken as 0.1. After matching, a total of 699 patients were included for the analysis, including 128 patients in the neoadjuvant chemotherapy group, 267 patients in the adjuvant chemotherapy group, and 304 patients in the surgery alone group. The Kaplan-Meier method was used to generate the survival curves which was tested by the Log-rank method for survival analysis. Results: After matching analysis, the 5-year overall survival rate was 41.5% in the neoadjuvant chemotherapy group with a median overall survival time of 43 months (95%CI: 27 to 59 months), 57.6% in the adjuvant chemotherapy group with a median overall survival time unreached, and 24.9% in the surgery alone group with a median overall survival time of 28 months (95%CI: 25 to 31 months) (χ²=60.475, P<0.01). For overall survival after matching, the adjuvant chemotherapy group was better than the neoadjuvant chemotherapy group (χ²=11.384, P=0.001), the neoadjuvant chemotherapy group was better than the surgery alone group (χ²=8.654, P=0.003), and the adjuvant chemotherapy group was better than surgery alone group (χ²=60.234, P<0.01). Conclusion: Both preoperative neoadjuvant chemotherapy and postoperative adjuvant chemotherapy can improve the long-term survival of patients with locally advanced esophageal squamous cell carcinoma undergoing radical resection, and the improvement effect of postoperative adjuvant chemotherapy is more obvious.

[Research progress on immune pathogenesis of pneumoconiosis].

Pneumoconiosis is a type of occupational disease with extensive influence and serious harm. It is a systemic disease of diffuse pulmonary fibrosis caused by the inhalation of industrial dust into the lungs, and pneumoconiosis can continue to progress without further dust exposure, eventually leading to respiratory failure and death. With the wide application of new materials, new technologies and new crafting, the increasing demand for industrial materials, the survival of a large number of dust-exposed workers during the industrial boom in the 20th century, the incidence and cumulative number of pneumoconiosis cases continued to remain high, which caused a vast economic burden to the society. The pathogenesis of pneumoconiosis is relatively complex and known to be related to mechanical stimulation, oxidative stress, inflammation, immune response, and genetic predisposition. The immune system, as the defense of the body, plays an important role in the development of pneumoconiosis. This paper reviews the recent progress on the immunological pathogenesis of pneumoconiosis.

[The relationship between resting heart rate and all-cause mortality among the Chinese oldest-old aged more than 80: a prospective cohort study].

Objective: To explore the association between resting heart rate(RHR) and all-cause mortality among the Chinese oldest-old aged more than 80. Methods: Using a total of seven surveys or follow-ups data (1998, 2000, 2002, 2005, 2008, 2011 and 2014) from the Chinese Longitudinal Healthy Longevity Survey (CLHLS). A total of 17 886 elderly over 80 years old were selected as subjects, their resting heart rate were measured though baseline survey and the survival outcome and death time of the subjects were followed up. The subjects were divided into 6 groups according to their resting heart rate. Cox regression model was used to estimate the effect of resting heart rate on mortality risk. The interaction of age, gender and resting heart rate was also analyzed by likelihood ratio test. Results: The age of subjects M (P25, P75) was 92 (86, 100) years old, including 10 531 females (58.9%) and there were 13 598 participants died, the mortality rate was 195.5 per 1 000 person-years. Multivariate Cox regression analysis showed that compared to the control group (60-69 pbm/min), the hazard ratio of the elderly are 1.06 (95%CI: 1.02, 1.11), 1.09 (95%CI: 1.04, 1.15), 1.23 (95%CI: 1.14, 1.34), 1.25 (95%CI: 1.08, 1.44) in the group of RHR between 70-79, 80-89, 90-99 and ≥100 pbm/min and P values are all less than 0.05. Likelihood ratio test showed that RHR and age had an interaction effect. (P for interaction=0.011). Conclusion: The risk of all-cause death increased with the increase of resting heart rate and this relationship was stronger between the 80-89 years old people.

Bibliometric Analysis of Forensic Genetics Literatures in SCIE from 1989 to 2019.

ABSTRACT: Objective To conduct bibliometric analysis of forensic genetics literatures published by Chinese mainland scholars in SCIE journals from 1989 to 2019, to show the research achievements of the past three decades and predict future research fields and directions. Methods Microsoft Office Excel 2019 was utilized to analyze the general situation, research institutions, authors, funds, author keywords, etc. of the literatures. The status of research in forensic genetics in Chinese mainland was visualized by PlotDB, Gephi 0.9.2 software and literature interpretation. Results During the last three decades, 1 126 forensic genetics literatures were published by scholars from Chinese mainland on SCIE journals, mostly articles. The quantity and quality of the literatures were both on the increase. The number of literatures published in Forensic Science International-Genetics was the highest, and 60.83% of the literatures were funded, mainly by the National Natural Science Foundation of China （498 literatures）. The current research hotspots were STR, SNP, InDel polymorphisms, linkage genetic markers, mtDNA genetic markers, epigenetic markers, RNA genetic markers, chip technology and omics research method. Conclusion The forensic genetics in China has developed rapidly along with the promotion of forensic science in universities. The SCIE literatures on forensic genetics published by Chinese mainland scholars increased rapidly with the funding from the National Natural Science Foundation of China and Ministry of Science and Technology of the People's Republic of China, which positively contributes to the development of basic research and the improvement of overall level in forensic genetics in China.

[Application of adaptive statistical iterative reconstruction veo and 80 kv in renal computed tomography angiography].

Objective: To explore the application of adaptive statistical iterative reconstruction Veo (ASIR-V) and 80 kV in renal computed tomography angiography(CTA). Methods: Eighty patients with renal computed tomography angiography were prospectively collected from April 2018 to July 2018 in the Affiliated Hospital of Shaanxi University of Chinese Medicine and randomly divided into group A and group B. The patients in group A adopted tube voltage 120 kV and contrast agent concentration 600 mgI/kg and reconstructed with filtered back projection (FBP), while the patients in group B were scanned with tube voltage 80 kV and contrast agent concentration 350 mgI/kg and reconstructed with FBP and ASIR-V from 10% to 100% with 10% interval. The CT values and standard deviation (SD) of the right renal artery, left renal artery were measured respectively to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).The image quality of renal CTA was subjectively scored by two experienced radiologists blindly using a 5-point criteria.The contrast agent,CT volume dose index(CTDI(vol)) and dose length product(DLP) in both groups were recorded and the effective radiation dose(ED) was calculated. Results: The ED ((2.11±0.19)mSv) and contrast agent ((21.9±3.0)g) in group B were 65.1% (P<0.05) and 42.2% (P<0.05) lower than those in group A ((6.04±1.89)mSv and (38.0±3.8)g).With the increase of ASIR-V percentage in group B, CT values showed no significant difference, SD values gradually decreased, SNR values and CNR values gradually increased.The CT values with different reconstruction algorithm showed no statistically significant difference (all P>0.05) between group A and group B. The SD values with 40%ASIR-V to 100%ASIR-V reconstruction in group B were significantly lower than those of group A (all P<0.05).The SNR values with 50% ASIR-V to 100% ASIR-V reconstruction and CNR values with 70%ASIR-V to 100%ASIR-V were significantly higher than those of group A(all P<0.5).Two radiologists had excellent consistency in subjective scores of image quality for renal CTA(all kappa>0.75, P<0.05). The subjective scores with 60% ASIR-V to 90% ASIR-V in group B were significantly higher than those in group A (P<0.05), of which 70%ASIR-V reconstruction achieved the highest subjective score for renal CTA. Conclusion: ASIR-V and 80 kV can significantly reduce radiation dose (about 65.1%) and contrast agent (about 42.2%) in renal CTA, ASIR-V reconstruction can significantly improve the image quality of renal CTA, of which 70% ASIR-V reconstruction achieved the best image quality in 80 kV renal CTA.

[Clinicopathologic features and immunophenotype of pseudosarcomatous myofibroblastic proliferation of urinary bladder].

Objective: To investigate the clinicopathologic features, immunohistochemical phenotypes and biological behavior of pseudosarcomatous myofibroblastic proliferation (PMP) of the urinary bladder which may be misdiagnosed as a malignant neoplasm and undergo extensive treatment. Methods: Six cases of PMP of the urinary bladder were collected from 2001 to 2016 at Beijing Tiantan Hospital, Capital Medical University. The clinicopathologic features and immunophenotypic profile were studied by histopathological and immunohistochemical investigations with clinical follow-up. At the same time, the translocation of ALK gene was detected by fluorescence in situ hybridization (FISH). Immunohistochemistry was carried out using EnVision method for the expression of AE1/AE3, vimentin, EMA, SMA, Caldesmon, Calponin, desmin, ALK, Ki-67, MyoD1, myoglobin, CD34, S-100, CD117, CK7, CK20, GATA3, p63 and CK5/6. The related literature was reviewed. Results: There were two male and four female patients, significantly more common in women. The age of the patients was 27 to 53 years, and the median age was 35 years. The main clinical symptom was painless gross hematuria, one case with dysuria, and one case showed recurrent cystitis. There was no history of surgery and trauma. Follow-up ranged from 4 months to 13 years and showed five cases without recurrence and one case with recurrence. Microscopy showed submucosal lesion with inflammatory exudate and bleeding on the surface, in some cases extending to the superficial muscles of the bladder wall. The lesion was characterized by the proliferation of plump spindle cells, which were loose or dense in arrangement. There were varying degrees of acute and chronic inflammatory cells infiltration in the myxoid matrix. Spindle cells arranged in disorder, or a dense stranding, especially abundant in the cell region. The median mitotic rate was <2/10 HPF cells, but there were no pathological mitotic figures and without nuclear atypia in most spindle cells. Spindle cells with eosinophilic cytoplasm showed long tapering cytoplasmic projections. Oval or short spindle nuclei had vacuolization with prominent nucleoli, looking like ganglionic cells. There were scarce collagen fibers, and a few spindle cells degenerated with chromatin blurred. Some areas showed a granuloma-like pattern and neutrophils within vascular cavity. Immunohistochemically, the spindle cells were diffusely positive for vimentin, SMA and caldesmon. CKpan was strongly and diffusely positive. Desmin and calponin expression was varying. Ki-67 positive cells were about 35% to 55%, but the spindle cells were negative for myoglobin, S-100, CD117, CD34, p63 and CK5/6. FISH test showed that there was no ALK isolated signal in 6 cases of PMP, and so no positive cases were found. Conclusions: PMP of the urinary bladder is a benign non-neoplastic myofibroblastic proliferative lesion. Morphology is extremely easy to be misdiagnosed as malignant tumors, and therefore more attention should be paid to avoid this misdiagnosis.

[Effects of cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome of in vitro fertilization-embryo transfer cycle].

OBJECTIVE: To investigate the impact of previous cystectomy for ovary benign cyst on ovarian reserve and pregnancy outcome in in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles. METHODS: Totally 622 infertility patients were retrospectively investigated who underwent first IVF/ICSI-ET cycle in Reproductive Hospital Affiliated to Shandong University from January 2013 to June 2014. There were 153 cases who had been removed ovarian cyst by cystectomy surgeries recruited as study group, in which 44 cases of ovarian endometriosis cyst, 35 cases of benign ovarian teratomas, 67 cases of simple ovarian cyst and 7 cases of ovarian mucinous cystadenoma. In contrast, 469 infertility patients with tubal-factor infertility or male factor were included as control group. The age-matched women in the control group had no ovarian surgery previously. The indicators of ovarian reserve and pregnancy outcome were analyzed between two groups. The influence of different types of ovarian cysts on ovarian reserve and pregnancy outcome in IVF/ICSI-ET cycles were also studied, ovarian endometriosis cyst was studied as Group A, and Group B consisted of benign ovarian teratomas, simple ovarian cyst and mucinous cystadenoma. RESULTS: (1) The significantly lower serum antimullerian hormone (AMH) level (median: 1.92 versus 2.90 mg/L), antral follicle count (AFC; median: 12.0 versus 13.0), retrieved oocytes (12±5 versus 13±6) and the number of embryo cryopreserved (median: 1.0 versus 3.0) were found in study group compared with control group (all P<0.05). There was no statistical difference between two group for the following parameters, such as basal FSH level, the total dosage of gonadotropin duration and the total dosage of gonadotropin (all P>0.05). A better clinical pregnancy rate was achieved in control group (61.6%, 241/391) than that in study group (61.4%, 81/132), but no significant difference was existed (P=0.96). (2) Compared to Group B, Group A had fewer AFC, lower serum AMH level, retrieved oocytes and the number of embryo cryopreserved (11±4 versus 13±5; 1.65 versus 2.15 mg/L; 9±4 versus 13±5; 0 versus 2.0; all P< 0.01). There was a lower clinical pregnancy rate in Group A than that in Group B [50.0% (19/38) versus 66.0% (62/94)], accompanying with higher abortion rate [3/19 versus 9.7% (6/62)], but no differences were observed (all P>0.05). CONCLUSIONS: Ovarian reserve declines after the cystectomy for ovarian benign cysts and the cystectomy has a negative impact on IVF/ICSI-ET cycle, resulting in a decrease of the number of retrieved oocytes and the number of embryo cryopreserved, but do not influence clinical pregnancy outcome. Ovarian reserve is impaired more seriously by cystectomy for ovarian endometriosis cyst than other ovarian benign cyst.

Expression profiles of differentially expressed genes affecting fecundity in goat ovarian tissues.

Although RNA-Seq is an effective method for identifying and exploring novel functional genes in mammals, it has rarely been applied to study fertility-related genes in the goat. In this study, RNA-Seq was used to screen the estrus ovaries of uniparous and multiparous Anhui white goats (AWGs). In total, 15,890 genes were identified and 2201 of these were found to be differentially expressed between the genetic libraries from uniparous and multiparous goats. Compared to the uniparous library, 1583 genes were up-regulated and 618 genes were down-regulated in the multiparous library. The FER1L4 gene showed the level of highest up-regulation in the multiparous library, while SRD5A2 expression showed the greatest down-regulation. In order to determine the functions of FER1L4 and SRD5A2 in goats, the expression profiles of the two genes in different tissues from AWGs and Boer goats at diestrus were analyzed by quantitative PCR. FER1L4 and SRD5A2 showed tissue specific expression patterns and were highly expressed in ovaries from both AWGs and Boer goats. FER1L4 was more highly expressed in ovaries from multiparous than uniparous AWGs. In contrast, SRD5A2 was expressed at a lower level in multiparous AWGs. These results indicated that FER1L4 and SRD5A2 may be associated with the high fecundity of AWGs.

Identification of complete linkage disequilibrium in the DSG4 gene and its association with wool length and crimp in Chinese indigenous sheep.

The desmoglein 4 (DSG4) gene is a potential candidate in the search for genes that may affect wool traits, because of its function. This study aimed to screen for polymorphisms in partial exon 16 and 3ꞌUTR of the sheep desmoglein 4 DSG4 gene, and to test its possible association with wool length and crimp associated with fur. Overall, 326 sheep were scanned via single-strand conformational polymorphism assay, through three pairs of primers. The breeds included Tan, Han, and TanxHan from China, Polled Dorset from Australia, and Suffolk from Britain genotypes AA, BB, and AB for primer2 and genotypes DD, EE, and DE for primer3 were detected in native breeds. Six SNPs and 3-bp insertion/deletions were found in exon 16, of which 4 lead to amino acid substitutions. In addition, 1 SNP was found in 3ꞌUTR. The DSG4 genotype was found to be strongly associated with all wool traits that were considered in this study (P < 0.01). Sheep with the genotype MM had a higher least square mean compared to sheep with the genotype WW or WM with respect to birth scapular wool length (P < 0.01), crimp number of birth scapular wool crimp (P < 0.01), crimp number of weaning scapular wool crimp (P < 0.01), and crimp number of weaning rump wool crimp (P < 0.01, P < 0.05). In conclusion, our study is the first to demonstrate that the DSG4 gene may be a candidate, or major gene, which influences important wool traits.

The diagnostic efficiency of diffusion-weighted imaging in placenta accreta spectrum: a systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the diagnostic efficiency of diffusion-weighted imaging (DWI) in patients with placenta accreta spectrum (PAS). MATERIALS AND METHODS: The present study searched on PubMed, Embase, OVID, Cochrane, Scopus and CNKI, Chinese Bio-Medical Literature, VIP, Wanfang, Duxiu, databases for studies related to the diagnostic performance of DWI for PAS from inception to December 2022. The pooled sensitivity, the pooled specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnosis odds ratios (DOR) were calculated by Meta-disc 1.4 and STATA 16.0. RESULTS: A total of 11 studies met the criteria and were included in the meta-analysis. The effect indexes of DWI in combined PAS were as follows. The pooled sensitivity was 0.670 (0.619-0.719). The pooled specificity was 0.720 (0.661-0.773). The pooled LR+ was 2.161 (1.454-3.211). The pooled LR- was 0.413 (0.280-0.609). The pooled AUC was 0.7841, and Q* was 0.7221. The pooled diagnostic ratio DOR was 6.713 (2.981-15.118). Subgroup analysis showed that four studies used T2-weighted imaging (T2WI) + DWI to diagnose PAS, and the pooled AUC was 0.9822. CONCLUSIONS: The results showed that DWI had high sensitivity and specificity in the diagnosis of PAS. Furthermore, T2WI+DWI has higher diagnostic efficacy than DWI alone in the diagnosis of PAS. Therefore, it is necessary to set T2WI+DWI as a routine sequence for PAS, and T2WI+DWI should be a routine method for the daily diagnosis of PAS.

[Efficacy of PD-1 inhibitors combined with nab-paclitaxel and cisplatin in the neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma].

Objective: To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation. Methods: Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m2) and cisplatin (60 mg/m2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results: The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95%CI: 74.0% to 94.8%) and 50.3% (95%CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95%CI: 88.9% to 100.0%) and 58.2% (95%CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95%CI: 74.2% to 94.9%) and 53.5% (95%CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion: The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.

Individualized treatment of NSCLC: from research to clinical practice.

The exact clinical significance of EGFR mutation status in NSCLC at the time of initial diagnosis remains disputable. The gene expression module in NSCLC for chemotherapy outcome prediction needs to be developed. We analyzed 56 patients with NSCLC received chemotherapy either with (n=20) or without EGFR-TKIs (n=36) between 2008 and 2012 in China. EGFR mutation test and gene expression profiling were performed in samples obtained before medication treatment by liquidchip platform. Significant association (P = 0.028) was seen between EGFR mutation status before first-line chemotherapy and EGFR-TKIs treatment outcomes, which even can be found from the status before second- or third-line treatment. A14-gene expression profiling had been studied. Patients with low mRNA expression of ERCC1 or TYMS preferred higher DCR to cisplatin and pemetrexed than those with high expression (P = 0.39 and P= 0.11). Highly co-expression of TUBB3 and STMN1 gene has associated with the resistance to antimicrotubule drugs (P = 0.03). Our data suggest the EGFR mutations status, even at the time of initial diagnosis, is predictive of outcomes of TKIs treatment after chemotherapy. The mRNA expression profiling investigated in this study has a predictive value in NSCLC treatment, but further research with expanded samples is still required.

Characterization of microRNAs from goat (Capra hircus) by Solexa deep-sequencing technology.

MicroRNAs (miRNAs) are an important class of small noncoding RNAs that are highly conserved in plants and animals. Many miRNAs are known to mediate a myriad of cell processes, including proliferation and differentiation, via the regulation of some transcription and signaling factors, which are closely related to muscle development and disease. In this study, small RNA cDNA libraries of Boer goats were constructed. In addition, we obtained the goat muscle miRNAs by using Solexa deep-sequencing technology and analyzed these miRNA characteristics by combining it with the bioinformatics technology. Based on Solexa sequencing and bioinformatics analysis, 562 species-conserved and 5 goat genome-specific miRNAs were identified, 322 of which exceeded 100 in the expression levels. The results of real-time quantitative polymerase chain reaction from 8 randomly selected miRNAs showed that the 8 miRNAs were expressed in goat muscle, and the expression patterns were consistent with the Solexa sequencing results. The identification and characterization of miRNAs in goat muscle provide important information on the role of miRNA regulation in muscle growth and development. These data will help to facilitate studies on the regulatory roles played by miRNAs during goat growth and development.

Polymorphisms of the myostatin gene (MSTN) and its relationship with growth traits in goat breeds.

Mutations in the myostatin (MSTN) gene can inactivate its expression and result in a non-functional protein, which leads to dramatic muscularity and a "double-muscling" phenomenon in many species. Using gene sequencing and polymerase chain reaction-single-strand conformation polymorphism methods, polymorphisms of the MSTN gene were investigated as a candidate marker for growth in 288 goats. The results showed 2 novel single nucleotide polymorphisms: DQ167575 g.197G>A and 345A>T. Three potential genotypes (AA, AB, and BB) of substitution 197G>A in the 5'-untranslated region were detected in the 2 breeds. The polymorphism (CC and CD) of substitution 345A>T in exon I was segregated. The genetic diversity analysis revealed that Boer goat and Anhui white goat possessed intermediate genetic diversity in the P1 and P3 loci. Significant associations between the genotypes of the P3 locus and body weight, body length, and body height were observed in Boer goat and Anhui white goat (P < 0.05). It could be inferred that the MSTN gene may be a major gene or linked to the major gene affecting the goat growth traits. The polymorphic site could be a molecular marker-assisted selection program for body weight.