Objective:To investigate the efficiency and safety of the pulsatile GnRH therapy in the treatment of male congeni-tal hypogonadotropic hypogonadism(CHH).Methods:We retrospectively analyzed the clinical data on 45 CHH males treated by pulsatile GnRH therapy in our hospital from January 2013 to March 2023.We treated the patients with gonadorelin at 7-15 μg,one pulse/90 min,and followed them up every month in the first 3 months and then every 3 to 6 months after treatment,for an average of 19.1±4.3 months,during which we recorded the height,body weight,penile length,testis volume,Tanner stages,levels of FSH,LH and T,semen parameters and adverse reactions of the patients,followed by comparison of the data obtained with the baseline.Results:The levels of FSH,LH and T of the patients were dramatically elevated after treatment(P<0.01).The T level of the6 ca-ses of cryptorchidism,however,failed to reach the normal value within 18.2±8.6 months of follow-up.Significant improvement was seen in the external genitalia and secondary sexual characteristics of all the patients,and spermatogenesis was observed in the semen in 33 cases(73.3% ),with a mean sperm concentration of(18.2±6.2)106/ml,sperm progressive motility of(19.7±6.5)%,and semen volume of(1.8±0.6)ml.Eight of the cases achieved natural fertility,and another 3 achieved childbirth by assisted re-productive technology.As for adverse events,gynecomastia was observed in 8,subcutaneous induration in 6,and allergic reaction to therapeutic agent in 3 cases.Conclusion:Pulsatile GnRH therapy is an effective and safe strategy for male CHH.However,clini-cians should choose appropriate approaches to different individual cases.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective To investigate the effects of glutathiones-transferase (GST) T1, GSTM1 and epoxide hydrolase (EPHX1) genes on skin injury in workers exposed to coal tar pitch. Methods Workers from a carbon manufacturing company involved in coal tar pitch production and use were selected as the study subjects using a judgment sampling method. Workers with skin injury after exposed to coal tar were selected as the case group (55 cases), and those with the same workshop and type of work but without skin abnormalities were selected as the control group (197 cases). Urine and blood samples were collected from the workers, and levels of polycyclic aromatic hydrocarbon metabolites, including 1-pyrenol (1-OH-P), 1-naphthol (1-OH-N) and 2-naphthol (2-OH-N), in urine were measured using ultra high-performance liquid chromatography tandem mass spectrometry. The GSTT1, GSTM1 and EPHX1 genes in blood were detected by polymerase chain reaction. Results In the case group, all 55 workers reported skin stinging, 25 workers reported itching and flaking, and 15 workers reported blackheads and pigmentation. Urinary levels of 1-OH-N and 2-OH-N were lower in the worker in the case group than that in the control group (all P<0.05). However, there was no significant difference in the level of 1-OH-P between the two groups (P>0.05). There were significant differences in the number of workers with GSTT1, GSTM1 and EPHX1(His139His) genes between the two groups (all P<0.01). The GSTT1 and GSTM1 genes were positively correlated with post-shift urinary levels of 1-OH-N, 1-OH-P, and 2-OH-N (all P<0.01). The EPHX1 (139Arg locus) gene was positively correlated with post-shift 2-OH-N levels (P=0.03). The GSTT1, GSTM1, and EPHX1 (139Arg locus) genes were associated with reduced skin damage among coal tar workers (all P<0.01), after controlling for age, length of service, gender, smoking, and alcohol consumption. Conclusion Exposure to coal tar pitch can cause skin injury in workers, and the GSTT1, GSTM1, and EPHX1 (139Arg locus) genes are protective factors against skin injury in those workers.

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.
Pregnancy ; Infant, Newborn ; Female ; Humans ; Body Mass Index ; Overweight/epidemiology* ; Premature Birth/epidemiology* ; Pre-Eclampsia/epidemiology* ; Cohort Studies ; Eclampsia ; Incidence ; Risk Factors ; Thinness/epidemiology*

Objective: To explore the association between coagulation function indicators and placental abruption (PA) in different trimesters of pregnancy among preeclampsia-eclampsia pregnant women. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study and were diagnosed with preeclampsia, eclampsia and chronic hypertension with superimposed preeclampsia in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. The baseline and follow-up information were collected by questionnaire survey, and the coagulation function indicators in the first and third trimesters were obtained through medical records. The Cox proportional hazards model was used to analyze the association between the coagulation function indicators and PA. A restrictive cubic spline curve was used to draw the dose-response curve between the relevant coagulation function indicators and PA. Results: A total of 1 340 participants were included in this study. The age was (32.50±4.24) and the incidence of PA was 4.4% (59/1 340). After adjusting for relevant factors, Cox proportional hazards model showed that compared with the high-level classification of fibrinogen (FIB), participants within the middle-(HR=3.28, 95%CI: 1.27-8.48) and low-level (HR=3.84, 95%CI: 1.40-10.53) classification during the first trimester and within the low-level classification (HR=4.18, 95%CI: 1.68-10.39) during the third trimester were more likely to experience PA. Compared with the middle-level classification of pro-thrombin time (PT), the risk of PA in the participants within the low-level classification (HR=2.67, 95%CI: 1.48-4.82) was significantly higher in the third trimester. The restrictive cubic spline analysis showed a linear negative association between FIB and PA in the first and third trimesters, while PT and PA showed an approximately L-shaped association . Conclusion: Among pregnant women diagnosed with preeclampsia-eclampsia, the middle-and low-level classification of FIB in the first and third trimesters and the low-level classification of PT in the third trimester could increase the risk of PA.
Pregnancy ; Female ; Humans ; Pre-Eclampsia/diagnosis* ; Abruptio Placentae/epidemiology* ; Pregnant Women ; Eclampsia ; Cohort Studies ; Placenta

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.
Humans ; Irinotecan/therapeutic use* ; Oxaliplatin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Fluorouracil ; Colonic Neoplasms/chemically induced* ; Rectal Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Camptothecin/adverse effects*

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies