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 explore the clinical value of inflammatory prognostic index combined with dual-source CT perfusion imaging in predicting early response of hepatocellular carcinoma(HCC)after transcatheter hepatic artery chemoembolization(TACE).Methods A total of 25 patients with HCC,who met the inclusion criteria and received initial TACE at the First Affiliated Hospital of Dali University of China from November 2022 to November 2023,were prospectively collected.CT perfusion scan was performed before TACE as well as in 30-40 days after TACE,and blood routine and blood biochemical data were collected.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to evaluate postoperative enhanced CT manifestations.Patients obtaining complete remission(CR)or partial remission(PR)were classified as effective group(n=14),and patients obtaining stable disease(SD)or progression disease(PD)were classified as ineffective group(n=11).The differences in CT perfusion imaging parameters and inflammatory parameters between the two groups were analyzed,and the predictive values of preoperative CT perfusion imaging parameters and inflammatory parameters for postoperative early response of HCC were evaluated.The cutoff value was taken at the maximum Youden index.Univariate analysis and multivariate analysis were used to analyze the effect of CT perfusion imaging parameters,inflammatory parameters and clinical features on the prognosis.The nomogram prediction model was constructed by using R software.Results The post-TACE arterial liver perfusion(ALP),hepatic perfusion index(HPI),blood flow(BF)and blood volume(BV)were significantly lower than their pre-TACE values(all P＜0.05).Afer TACE portal vein perfusion(PVP)was obviously higher than that before operation(P＜0.05).No statistically significant differences in the mean transit time(MTT),flow extraction product(FED),C-reactive protein(CRP),albumin(ALB),neutrophil/lymphocyte ratio(NLR)and inflammatory prognosis index(IPI)existed between the pre-TACE values and post-TACE values(all P＞0.05).The pre-TACE ALP,BF and FED in the effective group were significantly higher than those in the ineffective group,while the pre-TACE CRP and IPI in the effective group were remarkably lower than those in the ineffective group(P＜0.05).There were no statistically significant differences in pre-TACE PVP,HPI,MTT,BV,ALB and NLR between the effective group and the ineffective group before(all P＞0.05).In the effective group,the pre-TACE ALP,HPI,BF,BV and FED were obviously higher than their post-TACE values(all P＜0.05)preoperative PVP was significantly lower than postoperation(P＜0.05),while no statistically significant differences in MTT,CRP,ALB,NLR and IPI existed between the pre-TACE values and the post-TACE values(all P＞0.05).In the ineffective group,the pre-TACE HPI was prominently higher than the post-TACE value(P＜0.05),while no statistically significant differences in ALP,PVP,BF,BV,MTT,FED,ALB,CRP,NLR and IPI existed between the pre-TACE values and the post-TACE values(all P＞0.05).The pre-TACE ALP,BF,BV,FED,CRP and IPI had high predictive values in judging early response of HCC after TACE(all P＜0.05),the AUC values were 0.831,0.779,0.740,0.753,0.779 and 0.805 respectively,and the optimal cutoffs were 33.280 mL/100 mL min,61.860 mL/100 mL min,5.885 mL/100 mL,29.725 mL/100 mL min,30.465 mg/L,1.885 respectively.ALP combined with CRP had the highest predictive value for post-TACE early response of HCC,with an AUC of 0.968(95％CI:0.906-1.000,P＜0.05),ALP combined with IPI could significantly improve the predictive value,with an AUC of 0.961(95％CI:0.894-1.000,P＜0.05),with the sensitivity and specificity being 0.929 and 0.909 respectively.Multivariate analysis showed that pre-TACE ALP and CRP were the independent influencing factors for post-TACE early response of HCC(P＜0.05).The nomogram prediction model constructed based on the pre-TACE ALP and CRP could effectively predict the post-TACE early response of HCC,and the AUC value was 0.968(95％CI:0.908-1.000).Conclusion ALP and CRP can be used to predict the post-TACE early response of HCC,and the combination use of ALP and CRP can significantly improve the predictive value.

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 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.

【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.

Plant adaptation to adverse environment depends on transmitting the external stress signals into internal signaling pathways, and thus forming a variety of stress response mechanisms during evolution. Brassinosteroids (BRs) is a steroid hormone and widely involved in plant growth, development and stress response. BR is perceived by cell surface receptors, including the receptor brassinosteroid-insensitive 1 (BRI1) and the co-receptor BRI1-associated-kinase 1 (BAK1), which in turn trigger a signaling cascade that leads to the inhibition of BIN2 and activation of BES1/BZR1 transcription factors. BES1/BZR1 can directly regulate the expression of thousands of downstream responsive genes. Studies in the model plant Arabidopsis thaliana have shown that members of BR biosynthesis and signal transduction pathways, particularly protein kinase BIN2 and its downstream transcription factors BES1/BZR1, can be extensively regulated by a variety of environmental factors. In this paper, we summarize recent progresses on how BR biosynthesis and signal transduction are regulated by complex environmental factors, as well as how BR and environmental factors co-regulate crop agronomic traits, cold and salt stress responses.
Arabidopsis/metabolism* ; Brassinosteroids/pharmacology* ; DNA-Binding Proteins/metabolism* ; Gene Expression Regulation, Plant ; Stress, Physiological

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.

Objective To investigate the distribution and drug resistance of carbapenem-resistant Enterobacteriaceae ( CRE) isolated from children in China. Methods CRE strains were collected in 10 ter-tiary children's hospitals of China from January 1, 2016 to December 31, 2017. Antimicrobial susceptibility of the clinical strains was detected with disk diffusion method ( KB method) and automated method. The re-sults were analyzed according to the Clinical and Laboratory Standards Institute ( CLSI) Standards published in 2017. WHONET 5. 6 software was used to retrospectively analyze the distribution characteristics and drug resistance of these strains. Results A total of 3065 CRE clinical strains were isolated from children with an overall prevalence of 7. 7％ and among them, 13. 5％ were isolated in neonatal group and 5. 8％ in non-neo-natal group. The detection rate of CRE in 2017 was higher than that in 2016 (9. 7％ vs 5. 7％). Among the 3065 CRE strains, there were 1912 strains of Klebsiella pneumoniae (62. 0％), 667 strains of Escherichia coli (22. 0％), 206 strains of Enterobacter cloacae (7. 0％), 56 strains of Klebsiella aerogenes (1. 8％) and 47 strains of Serratia marcescens (1. 5％). Most of the strains were isolate in neonatology departments including neonatal intensive care units (NICU) and intensive care units (ICU), accounting for 44. 8％ and 19. 7％, respectively. Respiratory tract (61. 8％), urine (19. 4％) and blood (5. 7％) specimens were the main sources of CRE isolates. Results of antimicrobial susceptibility test showed that the CRE strains were highly resistant to carbapenem antibiotics such as imipenem, meropenem and ertapenem, as well as penicillins and most cephalosporins (79. 6％-100％), especially those isolated in the neonatal group (P<0. 05). Children had relatively low resistance rates to aminoglycosides such as amikacin (19. 7％) and fos-fomycin (11. 9％), fluoroquinolones such as levofloxacin (37. 7％) and ciprofloxacin (43. 3％), and tige-cycline (3. 8％). Currently, no polymyxin B-resistant strains were isolated. Conclusions The prevalence of common CRE strains in children in 2017 was higher than that in 2016, especially in newborns. Drug re-sistance in CRE strains isolated from neonates to common antibiotics was more severe, suggesting that great attention should be paid to it and timely measures should also be taken.

Objective: To analyze the antimicrobial resistance profile in Chinese children. Methods: This was a prevalence survey. From January 1 through December 31, 2016, the isolates were collected from 10 tertiary children hospitals in China. Antimicrobial susceptibility testing was carried out by routine laboratory methods. The penicillin susceptibility of streptococcus pneumonia and Meropenem susceptibility of gram-negative bacteria were detected by E-test and disk diffusion method respectively. Antimicrobial susceptibility results were interpreted according to the criteria of Clinical and Laboratory Standards Institute (CLSI) Guideline 2016. The data of antimicrobial susceptibility testing of isolates from either the different patients (neonatal group and non-neonatal group) or various sources were analyzed by WHONET 5.6 software. Results: A total of 56 241 isolates were collected, of which 41.5% (23 328 isolates) were gram-positive organisms and 58.5% (32 886 isolates) gram-negative organisms. The five leading pathogens were Escherichia coli (7 995/56 214, 14.2%), Straphylococcus aureus (6 468/56 214, 11.5%), Streptococcus pneumonia (6 225/56 214, 11.1%), Haemophilus influenza (5 435/56 214, 9.7%) and Klebsiella pneumonia (4 523/56 214, 8.0%). The Meropenem resistance rates of Klebsiella pneumonia, Enterobacter cloacae, Escherichia coil, Pseudomonas aeruginosa, Acinetobacter baumonia isolates were 27.4% (326/1 189) , 8.1% (29/358) , 2.0% (27/1 362) , 19.5% (34/174) , 49.7% (230/463) in neonatal group and 15.4% (512/3 327) , 4.8% (40/841) , 2.3% (151/6 564) , 13.7% (252/1 840) , and 53.4% (860/1 611) in non-neonatal group. The Methicillin-resistant Staphylococcus aureus (MRSA) rates of neonatal group and non-neonatal group were 46.2% (649/1 404) and 33.3% (1 668/5 010) . The penicillin non-susceptible rates of Streptococcus pneumonia in the two groups were 17.6% (6/34) and 18.2% (1 121/6 158) respectively. The β-lactamase positive rates of Haemophilus pneumonia isolates in the neonatal group and non-neonatal groups were 33.8% (47/139) and 44.4% (2 345/5 282) respectively. Conclusion This investigation highlights the worrisome trend of antimicrobial resistance in children, especially among neonatal patients in China.

Objective: To describe the clinical characteristics of pneumococcal infections and drug resistance of Streptococcus pneumoniae isolates from children's hospitals, which would provide reference for preventing and treating pneumococcal diseases. Methods: This was a prevalence survey. In this study, the age, specimen type, monthly distribution characteristics, and antimicrobial resistance of Streptococcus pneumoniae isolates from 9 children's hospitals in China were investigated between January 1, 2016 and December 31, 2016. The WHONET 5.6 software was used to analyze the antibiotic susceptibility of Streptococcus pneumoniae. The comparison of rates was performed by Chi-square test. Results: A total of 6 200 isolates of streptococcus pneumoniae were obtained, namely, 95.1% (5 876/6 177) from the respiratory tract specimens, 2.2% (136/6 177) from blood specimens and 0.4% (24/6 177) from cerebrospinal fluid specimens. The isolates were mainly from children older than 1 and younger than 5 years (54.7%, 3 381/6 185) . Most of strains (33.2%, 1 184/3 563) were isolated in November, December and January. Streptococcus pneumoniae isolates were completely sensitive to vancomycin (100.0%, 6 189/6 189) , linezolid (100.0%, 6 030/6 030) , moxifloxacin (100.0%, 3 064/3 064) , highly sensitive to levofloxacin (99.8%, 5 528/5 540), ertapenem (98.8%, 3 024/3 061) and lowly sensitive to erythromycin (1.7%, 102/6 016), clindamycin (3.7%, 116/3 136), and tetracycline (5%, 244/4 877), respectively. According to the parenteral susceptibility breakpoints for non-meningitis isolates, the sensitivity of Streptocococus pneumoniae to penicillin from children's hospital of Chongqing Medical University (49.3%, 892/1 809) was significantly lower than those of other hospitals (χ²=1 268.161, P<0.05) . Conclusions Streptococcus pneumoniae is mainly isolated from respiratory tract, from children older than 1 and younger than 5 years and during November to January in tertiary children's hospital of China. The Streptococcus pneumoniae from children is highly sensitive to vancomycin, linezolid, moxifloxacin, levofloxacin. There are also significant differences in the sensitivity of penicillin for Streptococcus pneumoniae from different hospitals.