[Objective] To evaluate the effects of preoperative ureteroscopy (URS) on the prognosis of patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). [Methods] Data of 712 UTUC patients who received RNU in West China Hospital during May 2003 and Jun.2019 were retrospectively analyzed. Patients were divided into URS group (n=187) and non-URS group (n=525) according to whether URS was performed before RNU. Kaplan-Meier curves were used to analyze the overall survival (OS), cancer-specific survival (CSS), and intravesical recurrence-free survival (IVRFS). Cox proportional risk model was used for risk assessment. Subgroup analysis and interaction test were used to further verify the results. [Results] Significant differences were observed between the two groups in terms of body mass index (BMI), diabetes mellitus, surgical method, hydronephrosis, tumor location, tumor grade, lymph node metastasis, lymphovascular invasion and tumor diameter (P<0.05). Kaplan-Meier survival analysis showed that IVRFS was significantly lower in the URS group than in the non-URS group (P<0.001), and the difference was more pronounced in renal pelvis carcinoma (P<0.001); there were no differences in OS and CSS between the two groups (P>0.05). Cox multivariate regression showed that URS was an independent risk factor for intravesical recurrence (HR=2.12, 95%CI: 1.34-3.36, P<0.001). [Conclusion] Preoperative URS can increase the recurrence rate of UTUC, but it has no effect on the OS and CSS.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Thirty-six puerperas who underwent emergency cesarean section at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 24, 2020 to February 9, 2020, who all wore medical surgical masks, were retrospectively included in this study. Anesthesia management was performed under tertiary medical protection measures. A dedicated anesthesia equipment was separately sterilized. Narcotic drugs were used for one patient only, and disposable medical supplies were used for anesthetic supplies. Contact transmission should be avoided when a neonate required resuscitation, and early isolation and nucleic acid testing were provided for the neonates. The rate of suspected cases of novel coronavirus (2019-nCoV) was 11% , and the rate of clinically diagnosed cases was 17% before surgery. The rate of clinically diagnosed cases of 2019-nCoV was 22%, the rate of confirmed cases was 8%, and the total positive rate of diagnosis was 31% after surgery. The rate of neuraxial anesthesia was 86%, the rate of general anesthesia was 14%, the time of spinal puncture was (15±7) min, the time of tracheal intubation under general anesthesia was (2.1±1.3) min, the operation time was (95±36) min, and blood loss was (276±166) ml. The Apgar score of newborns was 8.8 ± 0.5. There was 1 neonate whose mother was diagnosed as having 2019 novel coronavirous disease after operation, an oropharyngeal swab specimen was obtained at 36 h of birth, and the swab was tested positive for 2019-nCoV by nucleic acid testing. As of February 10, 2020, an anesthesiologist involved in the operation was diagnosed to have infection by 2019-nCoV. In conclusion, diagnosis of 2019 novel coronavirous disease during pregnancy is more difficult, it is necessary to perform anesthesia management for cesarean section under tertiary medical protection. Although the difficulty in anesthesia operation is increased under tertiary medical protection, anesthesiologists can carry out standardized anesthesia management and guarantee the safety of maternal and infants and anesthesiologists themselves as long as they are rigorously trained and adhere to protective protocols.

Thirty-six puerperas who underwent emergency cesarean section at Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology from January 24, 2020 to February 9, 2020, who all wore medical surgical masks, were retrospectively included in this study.Anesthesia management was performed under tertiary medical protection measures.A dedicated anesthesia equipment was separately sterilized.Narcotic drugs were used for one patient only, and disposable medical supplies were used for anesthetic supplies.Contact transmission should be avoided when a neonate required resuscitation, and early isolation and nucleic acid testing were provided for the neonates.The rate of suspected cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was 11% , and the rate of clinically diagnosed cases was 17% before surgery.The rate of clinically diagnosed cases of SARS-CoV-2 was 22%, the rate of confirmed cases was 8%, and the total positive rate of diagnosis was 31% after surgery.The rate of neuraxial anesthesia was 86%, the rate of general anesthesia was 14%, the time of spinal puncture was (15±7) min, the time of tracheal intubation under general anesthesia was (2.1±1.3) min, the operation time was (95±36) min, and blood loss was (276±166) ml.The Apgar score of newborns was 8.8±0.5.There was 1 neonate whose mother was diagnosed as having coronavirus disease 2019 after operation, an oropharyngeal swab specimen was obtained at 36 h of birth, and the swab was tested positive for SARS-CoV-2 by nucleic acid testing.As of February 10, 2020, an anesthesiologist involved in the operation was diagnosed to have infection by SARS-CoV-2.In conclusion, diagnosis of coronavirus disease 2019 during pregnancy is more difficult, it is necessary to perform anesthesia management for cesarean section under tertiary medical protection.Although the difficulty in anesthesia operation is increased under tertiary medical protection, anesthesiologists can carry out standardized anesthesia management and guarantee the safety of maternal and infants and anesthesiologists themselves as long as they are rigorously trained and adhere to protective protocols.

Objective To understand the epidemiological characteristics of the novel coronavirus diseases 2019 (COVID-19), and to scientifically guide the prevention and control of COVID-19 in Hubei Province. Methods All COVID-19 cases reported online in Hubei Province as of March 31, 2020 were extracted from Hubei^'s Infectious Disease Information System. The epidemic curve, age and sex characteristics, and spatiotemporal distribution characteristics of the COVID-19 cases were analyzed. Results As of March 31, 2020, a total of 70 764 cases were reported in Hubei Province, including 49 195 confirmed cases. A total of 4 579 deaths occurred among the confirmed cases, and the reported case fatality rate was 6.47%. The peak of the onset of symptoms occurred from January 20 to February 14, 2020. The sex ratio of male to female of the confirmed cases was 0.99: 1, and most were 30-69 years old. The cases diagnosed before January 5 were mainly reported by Wuhan City. From January 6 to January 31, all counties and districts in the province reported that the incidence of confirmed COVID-19 cases began to rise, and about 50% counties reported that the morbidity rate of confirmed COVID-19 cases was over 10 cases per 100 000. The morbidity rate of COVID-19 cases rose rapidly between February 1-15, and then gradually reached its peak after February 16. Conclusion Wuhan City of Hubei Province first discovered and reported the COVID-19 outbreak. The onset of symptoms peaked in January 20 to February 14, and the 30-69 years old group was the key population. Many measures such as restricting personnel movement, reducing contact, and strengthening health education played an important role in controlling the outbreak of COVID-19 in Hubei.

SOCS3, a feedback inhibitor of the JAK/STAT signal pathway, negatively regulates axonal regrowth and inflammation in the central nervous system (CNS). Here, we demonstrated a distinct role of SOCS3 in the injured spinal cord of the gecko following tail amputation. Severing the gecko spinal cord did not evoke an inflammatory cascade except for an injury-stimulated elevation of the granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon gamma (IFN-γ) cytokines. Simultaneously, the expression of SOCS3 was upregulated in microglia, and unexpectedly not in neurons. Enforced expression of SOCS3 was sufficient to suppress the GM-CSF/IFN-γ-driven inflammatory responses through its KIR domain by attenuating the activities of JAK1 and JAK2. SOCS3 was also linked to GM-CSF/IFN-γ-induced cross-tolerance. Transfection of adenovirus overexpressing SOCS3 in the injured cord resulted in a significant decrease of inflammatory cytokines. These results reveal a distinct role of SOCS3 in the regenerating spinal cord, and provide new hints for CNS repair in mammals.

OBJECTIVE: To analyze the phenotype and genetic variants of a pedigree affected with hereditary protein C (PC) deficiency. METHODS: The protein C activity (PC:A) of the proband and her family members (a four-generation pedigree including 11 individuals) were tested by chromogenic substrate method, and the protein C antigen (PC:Ag) was detected with an enzyme-linked immunosorbent assay(ELISA). The 9 exons and flanking sequences of the protein C (PROC) gene were amplified by PCR and directly sequenced. Suspected mutation was validated by clone sequencing and in other members of the family. MutationTaster and ClustalX-2.1-win was used to analyze the pathogenicity and conservation of the mutation site,respectively. Three-dimentional protein model and amino acids interaction were analyzed with Swiss-PdbViewer software. RESULTS: The PC: A and PC: Ag of the proband were decreased to 46% (reference range: 70%-130%) and 50% (referencerange:70%-140%), respectively. Her grandmother,aunt, cousin and younger brother also showed declined PC:A and PC:Ag by approximately 50%. Genetic analysis revealed that the above individuals have all carried a deletional mutation c.1212-1212delG (p.Met364TrpfsX15) in exon 9 of the PROC gene which can cause replacement of Methionine at position 364 by Tryptophan and alteration of 15 downstream amino acids, and produce a premature stop codon at position 378. The score of MutationTaster was 1.000, indicating that the variant is pathogenic. Conservative analysis showed that the 15 altered amino acids are located in a conserved region across nine homologous species. Protein model analysis showed that the mutation has disrupted a catalytic domain of protein C thereby affected its function. CONCLUSION The heterozygous c.1212-1212delG deletional mutation in exon 9 of the PROC gene, which was unreported previously,probably accounts for the decrease of PC:A and PC:Ag in this pedigree.

Objective:To investigate the changes of T lymphocyte subsets and cytokines in children with he-patitis B virus(HBV)-associated glomerulonephritis (HBV-GN), and their relationship with HBV-DNA load.Methods:Forty-one children who was the first diagnosed with HBV-GN in Department of Pediatrics, the People′s Hospital of Gansu Province and Institute of Infectious Diseases, the First Hospital of Lanzhou University from September 2012 to September 2016 were collected as the objects(HBV-GN group). At the same time, the 40 patients with HBV infection (chronic HBV infection, normal liver and kidney function, normal 24-hour proteinuria quantitation, no hematuria under the microscope, no recent symptoms of cold and fever, etc.) were enrolled as the control group.The levels of T lymphocyte subset, tumor necrosis factor α(TNF-α), interferon-γ (IFN-γ), interleukin (IL)-2, IL-4, IL-6, IL-8 and IL-10 in the HBV-GN group and the control group were compared, and the relationship between HBV-DNA and cell factors was farther analyzed.Results:Compared with the control group, the proportions of CD3 + T, CD4 + T lymphocyte and CD4 + /CD8 + ratio decreased in the HBV-GN group(0.632±0.052 vs.0.692±0.047, 0.204±0.050 vs.0.466±0.038, 0.006±0.002 vs.0.017±0.003, t=1.025, 3.342, 5.234, all P<0.05), and the proportions of CD8 + T lymphocyte was significantly higher than that in the control group (0.411±0.023 vs.0.220±0.043, t=4.452, P<0.01). Besides, IL-2 and IFN-γ levels in the HBV-GN group were significantly lower than those in the control group[(23.36±2.55) ng/L vs.(36.33±1.24) ng/L, (19.20±2.18) ng/L vs.(61.25±2.08) ng/L, all P<0.05], and the serum levels of TNF-α, IL-4, IL-6, IL-8, and IL-10 were significantly higher than those in the control group[(19.60±1.46) ng/L vs.( 6.68±2.32) ng/L, (13.65±3.34) ng/L vs.(1.35±1.52) ng/L, (5.57±1.02) ng/L vs.(1.43±0.57) ng/L, (26.32±3.45) ng/L vs.(9.68±2.55) ng/L, (19.82±2.78) ng/L vs.(1.02±0.56) ng/L, all P<0.01]. Moreover, in HBV-GN patients, there was negative correlation between HBV-DNA load and IFN-γ, IL-2( r=-0.985, -0.943, all P<0.05), and positive relationship in HBV-DNA load with TNF-α, IL-4, IL-6, IL-8 and IL -10 levels( r=0.942, 0.966, 0.953, 0.944, 0.963, all P<0.05). Conclusions:There is an CD4 + /CD8 + imbalance and an abnormal level of cell factors in HBV-GN progression.In further HBV-GN treatment, HBV-DNA and the cell factors should be detected simultaneously to dynamically eva-luate the illness change and the clinical curative effect.