ObjectiveTo investigate the correlation between genetic polymorphism of heat shock proteins 70 (HSP70) and susceptibility to occupational noise-induced hearing loss (ONIHL). Methods A total of 229 ONIHL workers were selected as the case group and 229 healthy workers with similar age, years of noise exposure, and noise exposure levels were selected as the control group using the case-control study method. Occupational health examinations were conducted on both groups, and peripheral blood of individuals was collected for DNA extraction. The genotypes of three single nucleotide polymorphisms of the HSP70 were detected using the MassArray system. Results The allele frequency distribution of HSP70 rs2227956, rs1043618, and rs1061581 in the control group was in Hardy-Weinberg equilibrium (all P>0.05). The genotype and allele frequency distribution of rs2227956 was significantly different between the two groups (all P<0.05), while no significant difference was found for rs1043618 and rs1061581 (all P>0.05). After adjusting for age, years of noise exposure, individual noise exposure level, smoking, and drinking, individuals with AG and AG+GG genotypes of rs2227956 had a higher risk of ONIHL than those with AA genotype (all P<0.05). The risk of ONIHL was higher in individuals with G allele of rs2227956 than in those with A allele (P<0.05). No correlation was found between rs1043618 and rs1061581 polymorphisms and the risk of ONIHL (all P>0.05). Conclusion The rs2227956 polymorphism of the HSP70 gene is correlated with susceptibility to ONIHL in noise-exposed workers, and the G allele is a risk factor for ONIHL in this population.

Objective To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer(FET)cycles in patients with polycystic ovary syndrome(PCOS).Methods A retrospective analysis was conducted on patients'data from 882 FET cycles.According to the pregnancy outcome,the patients were divided into non-implantation group(Group A),abortion group(Group B1)and live birth group(Group B2).Clinical data and laboratory parameters were compared among the three groups,and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET.Patients were also divided into four groups(C1-C4)based on the number of high-quality embryos obtained(0-3,4-6,7-10,≥11),and their clinical data and laboratory parameters were compared.Results The clinical pregnancy rate,live birth rate,and miscar-riage rate in the 882 treatment cycles were 71.09%(627/882),61.68%(544/882),and 13.24%(83/627),respectively.Single-factor analysis showed significant differences in body mass index(BMI),infertility type,hu-man chorionic gonadotropin(hCG)day estradiol(E2)level,number of retrieved oocytes,and number of high-quality embryos among Groups A,B1,and B2(P<0.05).Further multiple Logistic regression analysis revealed that BMI(OR=1.046,95%CI:1.001-1.093,P=0.044)and a history of previous pregnancy(OR=1.417,95%CI:1.030-1.950,P=0.032)were independent risk factors for successful FET in PCOS patients,while an in-creased number of high-quality embryos was an independent protective factor for successful pregnancy.Based on the results of Group B2,compared to Group A,OR=0.920,95%CI:0.880-0.962,P=0.000;compared to Group B1,OR=0.923,95%CI:0.862-0.988,P=0.022.Compared with the other three groups(C1-C3),the total amount of gonadotropin(Gn)in the C4 group was the lowest and the number of oocytes obtained was the high-est(P<0.05).Multiple comparisons showed that Group C4 had lower BMI,follicle-stimulating hormone(FSH),very low-density lipoprotein(vLDL)levels,a higher luteinizing hormone and follicle-stimulating hormone(LH/FSH)ratio compared to Group C1(P<0.05).Group C4 had lower fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)levels compared to Group C3,and higher high-density lipoprotein-cholesterol(HDL-C)and apolipoprotein A1(Apo A1)levels compared to Groups C2 and C3(P<0.05).Con-clusion BMI,the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles.Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles.

Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis and molecular charac-teristics desmoid fibromatosis the breast(DFB).Methods The clinicopathological data and prognostic information of 26 pa-tients with desmoid fibromatosis of the breast were collected.Their clinical characteristics,histological morphologies,immu-nophenotypes and molecular characteristics were analyzed.Re-sults All the 26 patients were female,with a median age of 34.5 years and an average age of 36.8 years(range from 13 to 69 years).There were 10 cases in left breast,14 cases in right breast and 2 cases in bilateral breast.Isolated and painless breast masses were found in all patients,and 3 cases were ac-companied by nipple depression.Grossly,most of them showed a poorly circumscribed tan-white to gray mass with a trabeculated appearance.Microscopically,all the tumors were composed of mild spindle cells with varying intervals of collagen fiber bun-dles.The boundary between the tumor and the surrounding breast tissue was not clear,and the tumor cells infiltrated adja-cent tissues,such as breast ducts,lobules,adipose tissue,and skeletal muscle.Uniform spindle or oval cells formed in fascicles and interwoven,without atypical or polymorphism;the nuclear chromatin was sparse or vacuolar,with small nucleoli,but mito-ses were rare or absent.Nuclear accumulation of β-catenin was present in 20 of 26 tumors,SMA was variously positive in 20 of 26,desmin was focally positive in 6 of 26;CKpan,CK5/6,p63,CD34,CD10 and S-100 were all negative.The Ki67 index was 5％-10％.The gene mutations of CTNNB1 exon 3 were found in 18 of 26 by Sanger sequencing,including T41A(83.3％),S45P(11.1％)and S45F(5.6％).Two patients also had familial adenomatous polyposis.Local resection was performed in 23 cases,mastectomy was performed in 2 cases,and one case did not require any additional treatment after core needle biopsy.20 cases were followed up for 1-108 months,and no recurrence occurred.Conclusion Desmoid fibromatosis of the breast is rare,and can mimic breast cancer clinically,ra-diologically and histologically.It should be always considered in differential diagnosis for the spindle cell proliferations of the breast.A diagnosis of DFB can be achieved basing on the typi-cal histopathology,immunohistochemistry,history and gene se-quencing.

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.
Animals ; Male ; Testis ; Sertoli Cells/metabolism* ; Transcriptome ; Spermatogenesis/genetics* ; Primates ; Aging/genetics* ; Stem Cells

Objective To analyze the distribution characteristics of injuries among students in Songjiang district, Shanghai, and to provide data support for preventing injuries among students. Methods Data of injury cases among school students in Songjiang from 2017 to 2019 were collected from the National Injury Surveillance System (NISS), and the demographic characteristics, injury occurrence and clinical characteristics of injuries were analyzed. Results A total of 13 877 cases of injuries in school students were reported from 2017-2019, with a sex ratio of 1.94:1. The education level of the injured students was mainly primary school. The peak incidence months of student injuries were May (9.97%) and November (9.67%). Falls (50.83%) were the leading cause of student injuries, and the top three places of student injuries were at home (30.08%), in schools and public places (28.11%) and on roads/streets (22.97%). The top three activities at the time of the injury were leisure activities (34.62%), sports activities (18.50%), and taking transportation（17.68%）. The top three injury types were bruise/scratch (42.94%), sprain/strain (28.67%) and sharps/bite/open injury (13.53%). The common injury parts were lower limbs (38.39%), head (27.82%) and upper limbs (24.88%). Conclusion The prevention of injuries in school students in Songjiang should focus on male students and low age students, and targeted injury prevention and control work for students of different ages should be carried out.

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

Objective: To investigate the difference of clinical characteristics of recurrent spontaneous abortion (RSA) in patients with losses after spontaneous gestation and after in vitro fertilization and embryo transfer ( IVFET) ． Methods : 237 patients diagnosed with RSA were divided into spontaneous gestation group ( n = 185) and IVF group (n = 52) according to their previous modes of fertilization．The clinical characteristics of the two groups were analyzed. Results: Compared with the spontaneous gestation group，the age of the first pregnancy and the age at the time of RSA in the IVF group were statistically greater than those in the natural pregnancy group ( P < 0. 05 ) ．The number of biochemical pregnancies in IVF group was statistically higher than that in spontaneous gestation group，and the number of spontaneous abortions in IVF group was statistically lower than that in spontaneous gestation group (P＜0. 001) ．The proportion of patients with irregular menstruation in IVF group was statistically higher than that in spontaneous gestation group ( P ＜ 0. 05 ) ． The serum activated partial prothrombin time (APTT) ，R , K，high density lipoprotein cholesterol (HDL-C) ，thyrotropin (TSH) and homocysteine ( HCY) in IVF group were statistically lower than those in spontaneous gestation group，and the Angel，Ma，low density lipoprotein cholesterol (LDL-C) and body mass index (BMI) in IVF group were statistically higher than those in spontaneous gestation group (P＜0. 05) ．In the comparison of etiological composition between the two groups，the proportion of anatomical factors in IVF group was statistically higher than that in spontaneous gestation group (P < 0. 05) ． Conclusion The abortion risk factors in RSA patients after IVF-ET is more serious than that in RSA patients after natural pregnancy．It is suggested to further improve and implement the pre-pregnancy examination and education of infertile patients during IVF-ET treatment，so as to reduce the risk of RSA and obtain a better pregnancy outcome.

Objective : To analyze the metabolism of blood glucose，blood lipid and insulin in patients with recur- rent pregnancy loss (RPL) ，and to compare the predictive efficacy of triglyceride glycemic index (TyG) ，triglycer- ide glycemic body mass index (TyG-BMI) and homeostatic model assessment of insulin resistance( HOMA-IR) for RPL． Methods : A total of 573 patients with RPL were selected as the RPL group，and 652 women who received as- sisted reproductive technology for male infertility were selected as the control group．The general data of the two groups were retrospectively analyzed．The levels of body mass index(BMI) ，fasting blood glucose (FPG) ，fasting triglyceride (FTG) ，fasting insulin ( FINS) ，TyG index，TyG-BMI index and HOMA-IR were compared between the two groups．Spearman correlation analysis was used to verify the correlation between TyG index，TyG-BMI in- dex and HOMA-IR. Receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of TyG index，TyG-BMI index and HOMA-IR for RPL occurrence，and the optimal predictive cut-off point was calculated. Results : The BMI，FPG，FTG，TyG index，TyG-BMI index and HOMA-IR in the RPL group were significantly higher than those in the control group (P＜0. 05) ．TyG index and TyG-BMI index were positively correlated with HOMA-IR , and the correlation coefficients were 0. 442 and 0. 505，respectively (P＜0. 001) . ROC curve a- nalysis showed that the area under the curve of TyG-BMI index predicting RPL was 0. 579 (95% CI : 0. 551 - 0. 607，P＜0. 001) ，which was greater than that of TyG index of 0. 557 (95% CI : 0. 529－0. 585，P＜0. 001) and HOMA-IR of 0. 535 (95% CI : 0. 507 －0. 563，P ＜0. 05) ，among which the difference between TyG-BMI index and HOMA-IR index area under the curve was statistically significant (P ＜0. 05 ) ．The optimal cut-off points of TyG-BMI index ，TyG index and HOMA-IR for predicting RPL were 172. 3 ( sensitivity 75. 7% ，specificity 37. 06% ) ，8. 32 ( sensitivity 59. 44% ， specificity 51. 61% ) and 3. 58 ( sensitivity 25. 87% ， specificity 81. 62% ) ，respectively． Conclusion The incidence of overweight，abnormal blood glucose，lipid and insulin me- tabolism in RPL patients is higher than that in normal women．TyG index and TyG-BMI index can be used as indi- cators of insulin metabolic status in RPL population besides HOMA-IR , and TyG-BMI index has a higher efficacy in predicting the occurrence of RPL compared to HOMA-IR.

Objectives:To explore the GAA varient spectrum and the genotype-phenotype correlations in patients with glycogen storage disease type Ⅱ (Pompe disease, PD), as well as to estimate the disease incidence based on carrier rate of GAA varients in Guangzhou population.Methods:A total of 57 PD cases were retrospectively enrolled at Guangzhou Women and Children′s Medical Center from January 1, 2010 to May 31, 2020. All patients presented symptoms before the age of 18 years. Each diagnosis was further confirmed by GAA enzyme activity and GAA variants. The carrier rate of GAA varients was calculated based on variants detected by whole exon sequencing among 2 395 healthy children in Guangzhou.Results:Among the 57 PD patients (including male 26, female 31),twenty-eight patients with infantile onset PD (IOPD) presented with progressive general muscle weakness and cardiomyopathy. The mean ages of symptom onset and diagnosis were (2.5±1.4) and (5.0±3.0) months, respectively. Twenty-six cases died in the first year after birth.Twenty-three patients with late onset PD (LOPD) presented with progressive muscle weakness. Seven of them had respiratory failure at diagnosis. The mean ages of symptom onset and diagnosis were (12.0±5.0) and (17.0±7.5) years, respectively. Six children with atypical IOPD showed motor delay, muscle weakness and cardiomyopathy. Their diagnosis was confirmed at 2.5-7.0 years of age. Among the 57 patients, 47 different variants were identified in the GAA gene. Three variants: c.797C>T, c.1109G>A and c.1757C>T were novel. c.1935C>A (25/114, 21.9%) and c.2238G>C (15/114, 13.2%) were the most common variants, detected in 57.1% of IOPD and 65.2% (15/23) of LOPD patients, respectively. Among the 28 IOPD patients, 26 cases (92.9%) carried at least one missense variant which indicated positive cross-reactive immunologic material (CRIM). The carrier rate of pathogenic variants in GAA gene among healthy children was 24/2 395. The estimated incidence of PD in this population is about 1/40 000. The frequencies of pseudodeficiency variants c.1726G>A and c.2065G>A homozygotes were 26.3% (15/57) and 35.1% (20/57) in PD patients, which were significantly higher than those (1.7% (40/2 395) and 3.9% (94/2 395)) in healthy children (χ2=151.2, 121.9; both P<0.01). Conclusions:PD presents as a spectrum, some as atypical IOPD. The c.1935C>A and c.2238G>C are common variants, correlated with IOPD and LOPD respectively. The c.796C>T and c.1082C>T are usually found in atypical IOPD. The majority of IOPD patients is predicted to be CRIM positive. The estimated incidence of PD is about 1/40 000.

Objective:To evaluate and improve the performance of the newborn screening program for primary carnitine deficiency (PCD) based on tandem mass spectrometry and to investigate the incidence of PCD and molecular characteristics of SLC22A5 gene in Guangzhou.Methods:A total of 200 180 neonates born in Guangzhou from 2015 to 2019 were enrolled into the newborn screening program for PCD by tandem mass spectrometry at Guangzhou Newborn Screening Center. The positive results of screening for PCD was defined as free carnitine (C0) less than 10 μmol/L with decreased acylcarnitine species in dried blood spots of three to seven days after birth. Screen-positive newborns and their mothers were recalled for another blood spot sample. The diagnosis was confirmed based on decreased levels of C0 and acylcarnitine species in recalled blood spots and genetic analysis in SLC22A5 gene sequencing. The utility of using the sum of propionylcarnitine and palmitoylcarnitine (C3+C16) as a biomarker for acylcarnitine species in newborn screening was retrospectively evaluated. The levels of C0 and (C3+C16) at first screening were compared between newborns with PCD and newborns born to mothers with PCD by independent t test. The variant spectrum and known pathogenic variants carrier rate of SLC22A5 in 2 395 healthy children in Guangzhou Women and Children′s Medical Center through whole exon sequencing were analyzed. Results:Among 200 180 neonates, 239 (0.12%) cases were screen-positive for PCD. A total of 37 patients including 15 newborns and 22 mothers had confirmed PCD. The incidence of PCD was 1/13 345 in newborns and 1/9 099 in mothers, respectively. The positive predictive value of this program was 15.5%. Taking cutoff values of C0<8.5 μmol/L or C0 8.5~9.9 μmol/L with (C3+C16)<2 μmol/L, the number of screen-positive cases would be reduced from 810 to 224 without additional false negative case, when compared with cutoff value C0<10 μmol/L only. Both levels of C0 and (C3+C16) at first screening were not significant difference between newborns with PCD and newborns born to mothers with PCD ((6.2±2.4) vs. (5.0±1.8) μmol/L, (1.4±0.4) vs. (1.2±0.5) μmol/L, t=3.826, 0.326; P=0.058, 0.572). Seven PCD mothers experienced moderate fatigue and dizziness in the morning. One of them presented with cardiomyopathy in pregnancy. Genetic analysis of the SLC22A5 gene showed that p.S467C, p.F17L, p.R254X were the three most common variants in newborns with PCD. In PCD mothers and healthy children, the p.S467C, p.F17L and R399W were the three most common whereas the severe variant p.R254X was rare. The population carrier rate for pathogenic variants was 1 in 65 and the estimated incidence of PCD was about 1/16 500. Conclusions:Newborn screening can detect PCD both in newborns and mothers. Adding a quantitative biomarker (C3+C16) <2 μmol/L into the newborn screening program can improve the PCD screen performance. The severe variant p.R253X was common in PCD newborns but rare in PCD mothers and healthy children, indicating that the current screening program maybe failed to detect all PCD newborns and under-estimated the incidence rate of PCD in Guangzhou.