Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM＋EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P＜0.01); UCM＋EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P＜0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P＜0.05); ventricular remodeling was alleviated (P＜0.05), though there was no significant improvement in systolic function in UCM＋EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P＜0.01); the myocardial pathology improved with reduced collagen deposition in UCM＋EMPA group (P＜0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P＜0.01), while myocardial hypertrophy was alleviated in UCM＋EMPA group (P＜0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P＜0.05), but downregulated in UCM＋EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM＋EMPA group (P＜0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.

Objectives:To investigate the expression and clinical prognostic implication of secreted frizzled-related protein 4(SFRP4)in the peripheral blood of patients with dilated cardiomyopathy(DCM)and its.Methods:A total of 259 consecutive patients diagnosed with DCM who were admitted to the Cardiac Center of Zhongshan Hospital,Fudan University,from January 2017 to January 2019 were selected for the DCM group.Additionally,84 individuals who underwent health examinations and echocardiography at our hospital during this period,confirmed to be free of cardiovascular diseases,were selected as the control group.Peripheral serum samples were collected from both groups,and serum SFRP4 levels were measured using enzyme-linked immunosorbent assay(ELISA).The correlation between SFRP4 levels and DCM severity,as well as its predictive value for DCM prognosis,were analyzed.Results:Compared to the control group,the serum SFRP4 levels in the DCM group were significantly elevated([28.54±10.25]ng/ml vs.[52.70±19.74]ng/ml,P<0.05).The DCM group was randomly divided into a training set and a validation set in a 2:1 ratio.Multivariate logistic regression analysis in the training set revealed that serum SFRP4 levels were independently associated with all-cause mortality in DCM patients(OR=1.06,95% CI:1.03-1.10,P<0.001).We further evaluated the model's predictive performance with the receiver operating characteristic(ROC)curves(area under curve>0.8),calibration curves,and decision curve analysis,results indicated that the predictive model containing serum SFRP4 levels showed good performance on predicting all-cause mortality in DCM patients.Kaplan-Meier survival curve analysis demonstrated that during a median follow-up of 33.5(11.0,49.0)months,DCM patients with high peripheral blood SFRP4 levels(≥75th percentile)had a significantly higher incidence of all-cause mortality compared to those with low levels(<75th percentile)(28.81% vs.16.57%,P=0.02).Conclusions:The level of SFRP4 in the peripheral blood of DCM patients is significantly elevated,and peripheral serum SFRP4 levels have potential prognostic value for predicting the all-cause mortality in DCM patients.

Objectives:To investigate the expression and clinical prognostic implication of secreted frizzled-related protein 4(SFRP4)in the peripheral blood of patients with dilated cardiomyopathy(DCM)and its.Methods:A total of 259 consecutive patients diagnosed with DCM who were admitted to the Cardiac Center of Zhongshan Hospital,Fudan University,from January 2017 to January 2019 were selected for the DCM group.Additionally,84 individuals who underwent health examinations and echocardiography at our hospital during this period,confirmed to be free of cardiovascular diseases,were selected as the control group.Peripheral serum samples were collected from both groups,and serum SFRP4 levels were measured using enzyme-linked immunosorbent assay(ELISA).The correlation between SFRP4 levels and DCM severity,as well as its predictive value for DCM prognosis,were analyzed.Results:Compared to the control group,the serum SFRP4 levels in the DCM group were significantly elevated([28.54±10.25]ng/ml vs.[52.70±19.74]ng/ml,P<0.05).The DCM group was randomly divided into a training set and a validation set in a 2:1 ratio.Multivariate logistic regression analysis in the training set revealed that serum SFRP4 levels were independently associated with all-cause mortality in DCM patients(OR=1.06,95% CI:1.03-1.10,P<0.001).We further evaluated the model's predictive performance with the receiver operating characteristic(ROC)curves(area under curve>0.8),calibration curves,and decision curve analysis,results indicated that the predictive model containing serum SFRP4 levels showed good performance on predicting all-cause mortality in DCM patients.Kaplan-Meier survival curve analysis demonstrated that during a median follow-up of 33.5(11.0,49.0)months,DCM patients with high peripheral blood SFRP4 levels(≥75th percentile)had a significantly higher incidence of all-cause mortality compared to those with low levels(<75th percentile)(28.81% vs.16.57%,P=0.02).Conclusions:The level of SFRP4 in the peripheral blood of DCM patients is significantly elevated,and peripheral serum SFRP4 levels have potential prognostic value for predicting the all-cause mortality in DCM patients.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To investigate the diagnostic value of computed tomography(CT)combined with TaqMan probe for cardiopulmonary injury of pediatric patients with mycoplasma pneumonia of different clinical features.Methods:The medical records of 80 pediatric patients with mycoplasma pneumonia admitted to Shijiazhuang Maternal and Child Health Care Hospital from March 2020 to March 2023 were collected,and they were divided into<1 year old group(29 cases),1-3 years old group(23 cases)and>3 years old group(28 cases).They also were divided into long disease course group(43 cases,the disease course>7 d)and short disease course group(37 cases,the disease course≤7 d).All of pediatric patients underwent CT combined with TaqMan probe method to detect the cardiopulmonary injury,and to analyze the incidences of cardiopulmonary injury in pediatric patients of different age groups and different disease course groups.The CT and TaqMan probe were adopted to detect the pleural effusion,myocardial thickness,cardiothoracic ratio and the expression level of mycoplasma nucleic acid,and receiver operating characteristic(ROC)curves were adopted to analyze the diagnostic value of CT and probe in detecting cardiopulmonary injury of patients with mycoplasma pneumonia.Results:CT imaging showed that typical pulmonary abnormalities were present in patients of 62.5%,with a diagnostic accuracy of 93.75%(75/80),which main findings were pulmonary ground glass nodules(GGO),combined bacterial pneumonia and reticulation.Bronchiectasis was found in a small portion of patients.Bilateral pulmonary involvement was found in patients with pulmonary abnormalities,and the involvement of lower lobe was the most obvious in them.The 38 pediatric patients with clinically suspected incidental pulmonary embolism(PE)received additional CT examination with contrast agent,and the 24 pediatric patients of them were diagnosed as PE,and the diagnostic accuracy was 63.15%(24/38).TaqMan probe method was adopted to detect mycoplasma infection,and a high sensitivity and wide dynamic range detection system was established,which could conduct six times of dilutions for 10-fold between 0.2-0.2×10-5.Preparation was performed in 1 ng/μ l microbial community(MMC)-DNA standards,which had high linear dynamic range of 6 times of log10 dilutions with regression coefficient of R2=1.The detection lower limit was found to be 2×10-15 g/μl DNA.The incidence of cardiopulmonary injury gradually decreased with increasing age of pediatric patients with mycoplasma pneumonia of different ages.The incidences of cardiopulmonary injury in pediatric patients with mycoplasma pneumonia of<1 year old group,1 to 3 years old group and>3 years old group were respectively 93.10%,73.91%and 21.43%,and there were significant differences among the 3 groups(x2=7.660,33.019,P<0.05).The incidence(93.02%)of cardiopulmonary injury of long disease course group was significantly higher than that of short disease course group(27.03%),and the differences were statistically significant(x2=12.070,36.960,P<0.05),respectively.The amount of pleural effusion in the cardiopulmonary injury group was significantly higher than that in the non-cardiopulmonary damage group,and the myocardial thickness of cardiopulmonary injury group was significantly increased at the same time,and the cardiothoracic ratio of cardiopulmonary injury group was also significantly higher than that of non-cardiopulmonary injury group.There was significant difference in the expression level of mycoplasma nucleic acid(t=9.52,3.33,4.22,10.00,P<0.05).ROC curve analysis showed that the AUC value of CT combined with TaqMan probe method was larger than 0.5 in diagnosing cardiopulmonary injury of pediatric patients with mycoplasma pneumonia of different clinical features,and the AUC value of the combined diagnosis was largest.Conclusion:CT combined with TaqMan probe method has higher diagnostic value for the cardiopulmonary injury of pediatric patients with mycoplasma pneumonia.It should be considered to conduct the diagnosis of cardiopulmonary injury for pediatric patients who persistently exist the clinical symptom of mycoplasma pneumonia.The adaptation of existing TaqMan probe method,and the further expanded dPCR detection combination would improve the microbial diagnostic toolbox,which would provide reliable quantitative data for treatment decisions to cardiopulmonary injury of pediatric patients with mycoplasma pneumonia.

【Objective】 To analyze the effect of extensively hydrolyzed formula(eHF) in the treatment of feeding intolerance in preterm infants and the effect on hospital infection, in order to provide reference for the clinical treatment of feeding intolerance in preterm infants. 【Methods】 A total of 208 cases of preterm infants with feeding intolerance diagnosed and treated in Shandong Heze Municipal Hospital from April 2017 to February 2020 were selected into the clinical trial for eligibility assessment, then were randomly assigned into study group(n=100) and control group(n=100) after screening and exclusion. Children in the control group were fed with standard preterm formula, while children in the study group were fed with eHF. Feeding tolerance indicators, including daily milk intake, time to meconium evacuation, time to full gastrointestinal nutrition, total gastric residual counts(GRV1) in the 7-d period after resumption of breastfeeding, ratio of all-day gastric residual counts/all-day estimated milk intake after resumption of breastfeeding(GRV2) were compared between the two groups, and growth indicators(body weight growth rate, head dimension growth rate), complication incidence [necrotizing enterocolitis(NEC), pathological jaundice, positive fecal occult blood or blood in stool] and incidence of hospital-acquired infections. 【Results】 The daily milk intake(t=5.037) of the study group was higher than that of the control group, and the time of foetal excretion(t=9.217), the time to reach full gastrointestinal nutrition(t=15.833), GRV1(t=6.737), GRV2(t=9.956) were lower than those of the control group, and the differences were all statistically significant(P<0.05). The rate of weight gain(t=2.454) and head dimension growth(t=5.469) in the study group was significantly higher than those of the control group(P<0.05). The incidence of the three complications of NEC, pathological jaundice and positive fecal occult blood or blood in stool(χ²=4.310) and the incidence of hospital infections(χ²=4.688) were significantly lower in the study group than in the control group(P<0.05). 【Conclusions】 Compared with the standard formula milk for preterm infants, eHF can significantly improve the feeding intolerance of preterm infants, promote growth and development, and reduce the occurrence of hospital-acquired infections. Therefore, eHF can be widely used in clinic for preterm infants with feeding intolerance.

Objective To analyze the effect of night-shift work, anxiety and their interaction on work-related musculoskeletal disorders (WMSDs) among electronics manufacturing employees. Methods A total of 2 676 employees from 58 electronic manufacturing enterprises in the Pearl River Delta region of Guangdong Province were selected as the research subjects using the judgment sampling method. The Basic Situation Survey Scale, Generalized Anxiety Disorder 7-item Scale and Questionnaire of Musculoskeletal Disorders were used to assess night-shift work, anxiety and the prevalence of WMSDs in employees. The multivariate logistic regression model was used to analyze the effects of night-shift work, anxiety and their combined effects on the risk of WMSDs. Results The proportion of night-shift work was 30.3%, and the detection rates of anxiety and WMSDs were 26.8% and 41.3%, respectively. The results of multivariate logistic regression analysis showed that night-shift work and anxiety were independent risk factors of WMSDs in the research subjects, after excluding the influence of confounding factors such as age, marital status, enterprise size and length of service [odds ratio (OR) and 95% confidence interval (CI) were 1.307 (1.092-1.564) and 3.282 (2.739-3.934), respectively, both P<0.01]. Compared with those without night-shift work or anxiety, the risk of WMSDs was higher in individuals with only night-shift work, only anxiety, or both night-shift work and anxiety [OR and 95%CI were 1.347 (1.091-1.663), 3.395 (2.727-4.227) and 4.117 (3.072-5.519), respectively, all P<0.01]. Conclusion Both night-shift work and anxiety can increase the risk of WMSDs among electronic manufacturing employees, and these two factors exhibit a synergistic effect in increasing the risk of WMSDs.

Viscum coloratum (Kom.) Nakai is a well-known medicinal plant. However, the optimal harvest time for V. coloratum is unknown. Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control. Our study aimed to comprehensively evaluate the quality of V. coloratum in different growth stages, and determine the dynamic variation of metabolites. Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V. coloratum harvested in six growth periods, and the associated biosynthetic pathways were explored. The accumulation of different types of compounds were analyzed based on their synthesis pathways. Grey relational analysis was used to evaluate the quality of V. coloratum across different months. The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test. The results showed that the quality of V. coloratum was the hightest in March, followed by November, and became the lowest in July. During storage, compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids, leading to an increase followed by a decrease in the content of some compounds, and resulted in a large gap during the degradation time course among different compounds. Due to the rapid rate and large degree of degradation, five compounds were tentatively designated as "early warning components" for quality control. This report provides reference for better understanding the biosynthesis and degradation of metabolites in V. coloratum and lays a theoretical foundation for rational application of V. coloratum and better quality control of V. coloratum during storage.
Viscum/chemistry* ; Plants, Medicinal/chemistry* ; Chromatography, Liquid ; Mass Spectrometry ; Metabolomics

Objective:To explore the epidemiological characteristics of Streptococcus pyogenes, namely β-hemolytic Group A Streptococcus (GAS) in children in Shenzhen. Methods:Multilocus sequence typing (MLST) data on the epidemic clonal population of GAS infection in children in Shenzhen Children′s Hospital from January 2016 to December 2018 were retrospectively analyzed.In the present study, 32 GAS strains belonging to 7 different emm types were from 32 children′s with impetigo, cellulitis, scarlet fever, sepsis, pneumonia, obstructive sleep apnea hypopnea syndrome, bronchitis, allergy with rhinitis, buttock abscess, allergic purpura or pharyngeal tonsillitis, which were isolated from 23 throat swabs, 5 sputum samples, 3 pus and 1 blood.Using polymerase chain reaction technology, 7 pairs of allelic housekeeping genes ( gki, gtr, murI, mutS, recP, xpt and yqiL) of 32 GAS isolates were analyzed, and the target gene products were subjected to sequencing.Then the obtained gene sequences of each allele were submitted to the MLST database to obtain the allele profile.Finally, the allele profiles were introduced in the MLST database again to confirm the sequence typing (ST). Results:The GAS clone groups of emm 1.00 and its subtypes, emm 4.00, emm 12.00 and its subtypes, emm 22.00, emm 28.00, emm 75.00, and emm 89.00 belonged to the sequence typing ST28, ST39, ST36, ST46, ST52, ST49, and ST921, respectively. Conclusions:From 2016 to 2018, the MLST clone populations of GAS isolates causing infections in children in Shenzhen are classified as ST28, ST39, ST36, ST46, ST52, ST49 and ST921.