Objective To investigate the effect of glycine N-methyl transferase (GNMT)on intrauterine adhesion (IUA)fibrosis and its related mechanism.Methods In vivo experiment:A total of 36 healthy female SD rats (SPF grade,6～8 weeks old and weighing from 180～220 g)were subjected in this study.IUA model of SD rats and IUA model of GNMT overexpressed rats were established.RT-qPCR and immunofluorescence assay were applied to detect GNMT expression level in normal uterus and model group.RT-qPCR and Western blotting were used to detect the mRNA and protein levels of fibrosis-related molecules and the activation of TGF-β1/Smad3 signaling pathway in each group.The number of endometrial glands in each group was observed by HE staining.Masson staining was used to analyze the severity of endometrial fibrosis in each group.In vitro experiment:transformed human endometrial stromal cells (THESCs)fibrotic phenotype model was constructed using TGF-β1,and THESCs stably transfected with GNMT overexpression lentvirus were treated with TGF-β1.RT-qPCR and Western blotting were used to detect the mRNA and protein expression of fibrosis-related molecules.The expression of TGF-β1/Smad3 signaling pathway was detected by Western blotting.TGF-β1/Smad3 signaling pathway was activated by TGF-β1/Smad signaling pathway activator (SRI-011381),and the expression of TGF-β1/Smad3 signaling pathway and key molecular proteins of fibrosis phenotype was measured with Western blotting.Results In vivo experiment,the mRNA and protein expression levels of GNMT were significantly decreased in the IUA rats than the control rats (P<0.05).Overexpression of GNMT decreased the mRNA and protein levels of fibrosis related molecules,Collagen Ⅰ,Collagen Ⅲ and FN in the IUA rats (P<0.05),and decreased the phosphorylation levels of TGF-β1 and its downstream Smad3 protein (P<0.05).HE and Masson staining showed that overexpression of GNMT could increase the number of endometrial glands and reduce the severity of fibrosis in the IUA rats (P<0.05).In vitro experiments:overexpression of GNMT decreased the mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ and FN associated with fibrotic phenotype of THESCs (P<0.05),and reduced the phosphorylation level of Smad3 protein,downstream of TGF-β1 (P<0.05).After activation of TGF-β1/Smad3 signaling pathway,the protein levels of TGF-β1/Smad3 signaling pathway and downstream fibrosis phenotype molecules,Collagen Ⅲ and FN,were significantly decreased in the LV-GNMT+SRI-011381 group.Conclusion Overexpression of GNMT can inhibit endometrial fibrosis by regulating TGF-β1/Smad3 signaling pathway,thus achieving therapeutic effect on IUA.

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.
Male ; Humans ; Middle Aged ; Asparaginase/therapeutic use* ; Prognosis ; Retrospective Studies ; Lymphoma, Extranodal NK-T-Cell/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Etoposide ; Cyclophosphamide ; Methotrexate/therapeutic use* ; DNA/therapeutic use* ; Treatment Outcome

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100_L+2R-1, efu-miR-9226_L-2_1ss22GA, cgr-miR-1260_L+1, hsa-miR-652-3p_R+1, pal-miR-9993a-3p_L+2R-1, hsa-miR-7977_1ss6AG, hsa-miR-106b-3p_R-1, hsa-miR-186-5p, PC-3p-59611_111, hsa-miR-93-3p_R+1, and aeca-mir-8986a-p5_1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline.
Humans ; Male ; Young Adult ; Adult ; Middle Aged ; MicroRNAs/genetics* ; Signal Transduction/genetics* ; Spermatozoa/metabolism* ; Gene Expression Profiling

Objective: To investigate the epidemiology and hospitalization costs of pediatric community-acquired pneumonia (CAP) in Shanghai. Methods: A retrospective case summary was conducted on 63 614 hospitalized children with CAP in 59 public hospitals in Shanghai from January 2018 to December 2020. These children's medical records, including their basic information, diagnosis, procedures, and costs, were extracted. According to the medical institutions they were admitted, the patients were divided into the children's hospital group, the tertiary general hospital group and the secondary hospital group; according to the age, they were divided into <1 year old group, 1-<3 years old group, 3-<6 years old group, 6-<12 years old group and 12-18 years old group; according to the CAP severity, they were divided into severe pneumonia group and non-severe pneumonia group; according to whether an operation was conducted, the patients were divided into the operation group and the non-operation group. The epidemiological characteristics and hospitalization costs were compared among the groups. The χ² test or Wilcoxon rank sum test was used for the comparisons between two groups as appropriate, and the Kruskal-Wallis H test was conducted for comparisons among multiple groups. Results: A total of 63 614 hospitalized children with CAP were enrolled, including 34 243 males and 29 371 females. Their visiting age was 4 (2, 6) years. The length of stay was 6 (5, 8) days. There were 17 974 cases(28.3%) in the secondary hospital group, 35 331 cases (55.5%) in the tertiary general hospital group and 10 309 cases (16.2%) in the children's hospital group. Compared with the hospitalizations cases in 2018 (27 943), the cases in 2019 (29 009) increased by 3.8% (1 066/27 943), while sharply declined by 76.2% (21 281/27 943) in 2020 (6 662). There were significant differences in the proportion of patients from other provinces and severe pneumonia cases, and the hospitalization costs among the children's hospital, secondary hospital and tertiary general hospital (7 146 cases(69.3%) vs. 2 202 cases (12.3%) vs. 9 598 cases (27.2%), 6 929 cases (67.2%) vs. 2 270 cases (12.6%) vs. 9 397 cases (26.6%), 8 304 (6 261, 11 219) vs. 1 882 (1 304, 2 796) vs. 3 195 (2 364, 4 352) CNY, χ²=10 462.50, 9 702.26, 28 037.23, all P<0.001). The annual total hospitalization costs of pediatric CAP from 2018 to 2020 were 110 million CNY, 130 million CNY and 40 million CNY, respectively. And the cost for each hospitalization increased year by year, which was 2 940 (1 939, 4 438), 3 215 (2 126, 5 011) and 3 673 (2 274, 6 975) CNY, respectively. There were also significant differences in the hospitalization expenses in the different age groups of <1 year old, 1-<3 years old, 3-<6 years old, 6-<12 years old and 12-18 years old (5 941 (2 787, 9 247) vs. 2 793 (1 803, 4 336) vs. 3 013 (2 070, 4 329) vs. 3 473 (2 400, 5 097) vs. 4 290 (2 837, 7 314) CNY, χ²=3 462.39, P<0.001). The hospitalization cost of severe pneumonia was significantly higher than that of non-severe cases (5 076 (3 250, 8 364) vs. 2 685 (1 780, 3 843) CNY, Z=109.77, P<0.001). The cost of patients who received operation was significantly higher than that of whom did not (10 040 (4 583, 14 308) vs. 3 083 (2 025, 4 747) CNY, Z=44.46, P<0.001). Conclusions: The number of children hospitalized with CAP in Shanghai decreased significantly in 2020 was significantly lower than that in 2018 and 2019.The proportion of patients from other provinces and with severe pneumonia are mainly admitted in children's hospitals. Hospitalization costs are higher in children's hospitals, and also for children younger than 1 year old, severe cases and patients undergoing operations.
Infant ; Female ; Male ; Humans ; Child ; Retrospective Studies ; China/epidemiology* ; Hospitalization ; Community-Acquired Infections/therapy* ; Hospitals, Pediatric ; Pneumonia/therapy*

OBJECTIVE: To observe the effect of thumb-tack needles based on "Biaoben acupoint compatibility" on sequela symptoms, mental state and pulmonary ventilation function in patients with coronavirus disease 2019 (COVID-19) during recovery period. METHODS: Fifty cases of COVID-19 during recovery period were randomly divided into an observation group and a control group, 25 cases in each group. The patients in the observation group were treated with thumb-tack needles at Guanyuan (CV 4), Zusanli (ST 36) and Taiyuan (LU 9). The patients in the control group were treated with sham thumb-tack needles at identical acupoints as the observation group. The treatment in the two groups was given once a day, 7-day treatment was taken as a course of treatment, and totally two courses of treatment were given. The TCM symptom score, Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, pulmonary function (forced vital capacity [FVC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF]), the severity of pulmonary ventilation dysfunction and pulmonary imaging changes in the two groups were compared before and after treatment. RESULTS: Compared before treatment, the total scores and each item scores of TCM symptom scale, HAMA scores and HAMD scores in the two groups were reduced after treatment (P<0.05). Except for the symptom scores of dry throat and dry stool, the total score and each item score of TCM symptom scale, HAMA score and HAMD score in the observation group were lower than those in the control group (P<0.05). Compared before treatment, FVC, FEV1 and PEF in the two groups were increased after treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The severity of pulmonary ventilation dysfunction in the two groups was reduced after treatment (P<0.05), and the severity in the observation group was better than that in the control group (P<0.05). After treatment, the lung shadow area in the two groups was decreased (P<0.05), and that in the observation group was smaller than the control group (P<0.05). The improvement of imaging change in the observation group was better than that in the control group (P<0.05). CONCLUSION The thumb-tack needles based on "Biaoben acupoint compatibility" could significantly reduce the sequela symptoms, anxiety and depression in patients with COVID-19 during recovery stage, and improve the pulmonary ventilation function.
Acupuncture Points ; Anxiety/etiology* ; COVID-19/therapy* ; Depression/etiology* ; Humans ; Needles ; Respiratory Function Tests ; Thumb

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.
Adult ; Aged ; Aged, 80 and over ; China ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Proto-Oncogene Proteins c-bcl-6/genetics* ; Proto-Oncogene Proteins c-myc/genetics* ; Retrospective Studies

ObjectiveTo retrospectively analyze the clinical data of 52 patients with coronavirus disease-2019 （COVID-19） and explore the clinical efficacy of modified Sanxiaoyin on mild/moderate COVID-19 patients. MethodThe propensity score matching method was used to collect the clinical data of mild or moderate COVID-19 patients enrolled in the designated hospital of the Second Hospital of Jingzhou from December 2019 to May 2020. A total of 26 eligible patients who were treated with modified Sanxiaoyin were included in the observation group， and the 26 patients treated with conventional method were the regarded as the control. The disappearance of clinical symptoms， disappearance time of main symptoms， efficacy on traditional Chinese medicine （TCM） symptoms， hospitalization duration， laboratory test indicators， and CT imaging changes in the two groups were compared. ResultThe general data in the two groups were insignificantly different and thus they were comparable. After 7 days of treatment， the disappearance rate of fever， cough， fatigue， dry throat， anorexia， poor mental state， and poor sleep quality in the observation group was higher than that in the control group （P<0.05）， and the difference in the disappearance rate of expectoration and chest distress was insignificant. For the cases with the disappearance of symptoms， the main symptoms （fever， cough， fatigue， dry throat， anorexia， chest distress） disappeared earlier in the observation group than in the control group （P<0.01）. After 7 days of treatment， the scores of the TCM symptom scale of both groups decreased （P<0.01）， and the decrease of the observation group was larger that of the control group （P<0.01）. All patients in the two groups were cured and discharged. The average hospitalization duration in the observation group ［（12.79±2.68） d］ was shorter than that in the control group ［（15.27±3.11） d］ （P<0.01）. The effective rate in the observation group （92.31%， 24/26） was higher than that in the control group （76.92%， 20/26） . After 7 days of treatment， the lymphocyte （LYM） count increased （P<0.05）， and white blood cell （WBC） count and neutrophil （NEUT） count decreased insignificantly in the two groups. Moreover， levels of C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， and procalcitonin （PCT） reduced in the two groups after treatment （P<0.01） and the reduction in the observation group was larger than that in the control group （P<0.01）. Through 7 days of treatment， the total effective rate on pulmonary shadow in the observation group （90.00%， 18/20） was higher than that in the control group （77.27%， 17/22） （P>0.05） and the improvement of lung shadow in the observation group was better than that in the control group （P<0.01）. ConclusionModified Sanxiaoyin can significantly alleviate fever， cough， fatigue， anorexia， chest distress， poor sleep quality， and other symptoms of patients with mild or moderate COVID-19， improve biochemical indicators， and promote the recovery of lung function. This paper provides clinical evidence for the application of modified Sanxiaoyin in the treatment of mild or moderate COVID-19.

OBJECTIVE: To observe the clinical efficacy of dynamic qi acupuncture for acute lumbar sprain, and to explore the differences of different needle retention time on the improvement of pain, lumbar mobility and lumbar dysfunction. METHODS: A total of 160 patients with acute lumbar sprain were randomly divided into an observation group A (40 cases, 4 cases dropped off), an observation group B (40 cases, 2 cases dropped off), an observation group C (40 cases, 4 cases dropped off) and a medication group (40 cases, 6 cases dropped off). The patients in the observation group A, the observation group B and the observation group C were treated with acupuncture at "lumbago point" and Sanjian (LI 3) on the left side, and during the needles were kept for 10, 20 and 30 min respectively, the patients were required to take tolerable lumbar active activities, once a day; the patients in the medication group were treated with celecoxib capsules, 0.2 g each time, twice a day. All the patients were treated for 5 d. Before and after treatment, the scores of numerical rating scale-11 (NRS-11), lumbar range of motion (ROM) and modified Oswestry disability index (ODI) were observed, and the clinical efficacy of each group was evaluated. RESULTS: After treatment, the scores of NRS-11, ROM and ODI in each group were decreased compared before treatment (P<0.01). The decreased degree of NRS-11, ROM and ODI in each observation group was greater than that in the medication group (P<0.05), and the decreased degree of ROM and ODI in the observation group B and the observation group C was greater than that in the observation group A (P<0.05). The total effective rates were 94.4% (34/36) in the observation group A, 94.7% (36/38) in the observation group B and 97.2% (35/36) in the observation group C, respectively, which were higher than 79.4% (27/34) in the medication group (P<0.05). CONCLUSION Dynamic qi acupuncture with needle retention for 10, 20 and 30 min all could effectively improve the pain, lumbar mobility and lumbar dysfunction in patients with acute lumbar sprain. If the lumbar dysfunction is severe, needle retention for 20 min or more is recommended.
Humans ; Treatment Outcome ; Pain

OBJECTIVE: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. METHODS: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. RESULTS: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. CONCLUSION The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.
Middle Aged ; Male ; Humans ; Creatinine ; Cross-Sectional Studies ; Asian People ; Glomerular Filtration Rate ; China

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*