Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Objective To explore the effect of physical exercise on semen quality in order to provide basic data and theoretical basis for the improvement of male reproductive health.Methods A cross-sectional study was conducted on 1 059 males who visited the Reproductive Medicine Center of Shandong Maternal and Child Health Hospital for medical treatment and physical examination during July 2022 and April 2023.Their demographic data and physical exercise data were surveyed with questionnaires.Total sperm count,sperm concentration,total sperm motility,forward movement and normal sperm morphology were analyzed with computer aided analysis.Logistic regression model and multiple linear regression model were applied to analyze the effects of physical exercise on semen quality.Results After adjustment for confounding factors such as age,body mass index,alcohol consumption and smoking,logistic regression analysis showed that the risk of abnormal semen quality was increased in patients with moderate and heavy exercise intensity(OR=2.103,OR=2.229).Compared with the participants with physical exercise ≤10 min per session,those with＞20 min per session had a lower risk of abnormal semen quality(OR=0.357,0.256,0.289 for exercise time for＞20～30,＞30～60,＞60 min,respectively).There was no statistical significance between physical exercise frequency and semen quality(P＞0.05).The participants having exercise well were at a lower risk for abnormal semen quality(OR=0.711).Multiple linear regression analysis revealed that the frequency of physical exercise was an influencing factor of sperm concentration(β=7.474,95％CI:4.800～10.149,P＜0.05);the time of physical exercise per session was an influencing factor for total sperm count(β=20.632,95％CI:7.634～33.629);the intensity of physical exercise(β=-1.461,95％CI:-2.392～-0.530)and time of physical exercise per session(β=2.608,95％CI:1.404～3.812,P＜0.05)were influencing factors for percentage of forward motility sperm(P＜0.05);and physical exercise intensity(β=-1.934,95％CI:-3.238～-0.630),time of physical exercise per session(β=4.211,95％CI:2.525～5.897)and frequency of physical exercise(β=-2.008,95％CI:-3.480～-0.536)were influencing factors of total sperm motility(P＜0.05).Conclusion Physical exercise may affect semen quality,greater intensity of physical exercise may be a risk factor for abnormal semen quality,and longer physical exercise time may be related to improving semen quality.Therefore,proper physical exercise can help improve semen quality.

Objective:To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases.Methods:Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non-WBRT group). All patients received 4-6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM-OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no-WBRT groups. Survival analysis was estimated by Kaplan-Meier method, and the log-rank test was used to compare survival curves between two groups. Results:The median BM-OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non-WBRT groups, respectively( P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM-OS between two groups( P=0.02). In 118 patients with synchronous brain metastases, the median BM-OS in two groups were 13.0 months and 9.6 months( P=0.007); and in 127 patients with metachronous brain metastases, the median BM-OS were 8.0 months and 4.1 months( P=0.003). In 50 patients without extracranial metastases, the median BM-OS were 13.3 months and 10.9 months( P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM-OS were 9.5 months and 5.9 months( P=0.009)in two groups. Conclusions:WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.

Objective:To compare the incidence of radiation pneumonitis (RP) between lung cancer patients from the European, American and Asian regions.Methods:The studies related to lung cancer and RP were searched from PubMed, Embase, and Cochrane library. According to the different places where the studies were conducted, the searched studies were divided into two types: Asian studies and European, American and Australian studies. The incidence of RP between two regions was summarized. Studies related to dosimetry parameters were searched from PubMed database.Results:A total of 3, 190 patients from 14studies were included. Meta-analysis results showed that the incidence of ≥ grade 3 RP was similar in patients from Asia and Europe, America and Australia (4.9% vs. 4.6%, P=0.895), whereas the incidence of grade 5 RP in Asia was significantly higher than that in Europe, America and Australia (1.5% vs. 0.2%, P=0.002). Moreover, the lung irradiation dose received by the patients in the Asian group was relatively low. Lung V 20Gy dose limitation standard was reported in 21studies. Further analysis found no statistical significance in lung V 20Gy dose limitation standard between two regions ( P=0.440), and the standard in Asian studies is likely to be even stricter. Conclusions:The incidence of RP after chemoradiotherapy in lung cancer patients in Asia is relatively higher compared with those in Europe, America and Australia. The differences in dose limitation standard should be noted when the thoracic radiation regimen based solely on the data from foreign studies is applied to the patients in Asia.

OBJECTIVE: To explore the molecular basis for two brothers affected with globozoospermia. METHODS: Whole exome sequencing was carried out for both patients. Candidate variant was verified by Sanger sequencing and quantitative real-time PCR (qRT-PCR). RESULTS: Whole exome sequencing, Sanger sequencing and qRT-PCR verification revealed a heterozygous c.384dup (p.Glu129*) variant in the DPY19L2 gene in the two brothers and their mother. A large heterozygous deletion, spanning approximately 164.5 kb and encompassing the entire DPY19L2 gene, was detected on chromosome 12 of the two patients and their father. CONCLUSION The c.384dup (p.Glu129*) variant and deletion of the DPY19L2 gene probably underlie the pathogenesis of globozoospermia in the two patients, which was in keeping with the autosomal recessive inheritance of disease in this pedigree.
Gene Deletion ; Genetic Variation ; Humans ; Infertility, Male ; genetics ; Male ; Membrane Proteins ; genetics ; Pedigree ; Siblings ; Teratozoospermia ; genetics ; Whole Exome Sequencing

Objective:The existed economic evaluations of cancer screening in Chinese population are almost all single-cancer focused, evidence on parallel comparison among multiple cancers is lacking. Thus, the aim of this study was, from a priority setting perspective, to compare the cost-effectiveness of six common cancers(colorectal cancer, breast cancer, liver cancer, lung cancer, esophageal cancer and stomach cancer) to facilitate policy making in future scaled-up screening in populations in China.Methods:Partially based on our previous single-cancer systematic reviews (colorectal cancer, breast cancer, liver cancer, and lung cancer), evidence of economic evaluations of cancer screening in populations in mainland China were systematically updated and integrated. The main updates include: 1) Stomach cancer and esophageal cancer were newly added to the current analysis. 2) The literature searching was extended to 8 literature databases, including PubMed, EMbase, The Cochrane Library, Web of Science, CBM, CNKI, Wanfang Data, and VIP. 3) The period of publication year was updated to the recent 10 years: January 1, 2009 to December 31, 2018. 4) The study focused on populations in mainland China. Following the standard processes of literature searching, inclusion and exclusion from previous systematic reviews, the basic characteristics, evaluation indicators and main results of the included studies were extracted. All the costs were discounted to 2017 value using the by-year consumer price index of medical and health care residents in China and presented in the Chinese Yuan (CNY). The ratios of incremental cost-effectiveness ratio (ICER) to China′s per capita GDP in 2017 were calculated (<1 means very cost-effective, 1-3 means cost-effective, >3 means not cost-effective). Given a specific indicator, the median value among all reported screening strategies for each cancer was calculated, based on which priority ranking was then conducted among all cancers when data available.Results:A total of 45 studies were included, 22 for breast cancer, 12 for colorectal cancer, 6 for stomach cancer, 4 for esophageal cancer (all conducted in high-risk areas), 1 for liver cancer and none for lung cancer (was not then considered for next ranking due to limited numbers of studies). When based on the indicator, the median ratio of cost per life-year saved to China′s per capita GDP (reported in 12 studies), the lowest ratio (-0.015) was observed in esophageal cancer among 16 strategies of 2 studies ( N=2, n=16), followed by 0.297 for colorectal cancer ( N=3, n=12), 0.356 for stomach cancer ( N=1, n=4) and 0.896 for breast cancer ( N=6, n=52, P75=3.602). When based on another commonly used ICER indicator, the median ratio of cost per quality-adjusted life-year gained to China′s per capita GDP (reported in 13 studies), the least cost was found in stomach cancer (0.495, N=3, n=8, P75=3.126), followed by esophageal cancer (0.960, N=1, n=4, P75=1.762) and breast cancer (2.056, N=9, n=64, P75=4.217). Data was not found for colorectal cancer. In addition, cost per cancer case detected was the most adopted indicator (32 studies). The median cost among all screening strategies for each cancer was 14 759 CNY for stomach cancer ( N=5, n=7), 49 680 CNY for colorectal cancer ( N=12, n=25) and 171 930 CNY for breast cancer ( N=13, n=24), respectively. Data was not available for esophageal cancer and rare for precancer cases detected. Evidence related to cost per disability-adjusted life-year gained was not available. Conclusions:At China′s national level and limited to the six cancers covered by the current study, the preliminary analysis suggests that stomach cancer and colorectal cancer were the most cost-effective target cancers and could be given priority in the future scaled-up screening in general populations. Esophageal cancer screening should be prioritized in high-risk areas. Breast cancer was also cost-effective in general but some of the intensive screening strategies were marginal. Data on liver cancer and lung cancer were too limited to conclude, and more well-designed studies and high-quality research evidence should be required. This priority ranking might be changed if other common cancers were involved analyses.

Objective:The existed economic evaluations of cancer screening in Chinese population are almost all single-cancer focused, evidence on parallel comparison among multiple cancers is lacking. Thus, the aim of this study was, from a priority setting perspective, to compare the cost-effectiveness of six common cancers(colorectal cancer, breast cancer, liver cancer, lung cancer, esophageal cancer and stomach cancer) to facilitate policy making in future scaled-up screening in populations in China.Methods:Partially based on our previous single-cancer systematic reviews (colorectal cancer, breast cancer, liver cancer, and lung cancer), evidence of economic evaluations of cancer screening in populations in mainland China were systematically updated and integrated. The main updates include: 1) Stomach cancer and esophageal cancer were newly added to the current analysis. 2) The literature searching was extended to 8 literature databases, including PubMed, EMbase, The Cochrane Library, Web of Science, CBM, CNKI, Wanfang Data, and VIP. 3) The period of publication year was updated to the recent 10 years: January 1, 2009 to December 31, 2018. 4) The study focused on populations in mainland China. Following the standard processes of literature searching, inclusion and exclusion from previous systematic reviews, the basic characteristics, evaluation indicators and main results of the included studies were extracted. All the costs were discounted to 2017 value using the by-year consumer price index of medical and health care residents in China and presented in the Chinese Yuan (CNY). The ratios of incremental cost-effectiveness ratio (ICER) to China′s per capita GDP in 2017 were calculated (<1 means very cost-effective, 1-3 means cost-effective, >3 means not cost-effective). Given a specific indicator, the median value among all reported screening strategies for each cancer was calculated, based on which priority ranking was then conducted among all cancers when data available.Results:A total of 45 studies were included, 22 for breast cancer, 12 for colorectal cancer, 6 for stomach cancer, 4 for esophageal cancer (all conducted in high-risk areas), 1 for liver cancer and none for lung cancer (was not then considered for next ranking due to limited numbers of studies). When based on the indicator, the median ratio of cost per life-year saved to China′s per capita GDP (reported in 12 studies), the lowest ratio (-0.015) was observed in esophageal cancer among 16 strategies of 2 studies ( N=2, n=16), followed by 0.297 for colorectal cancer ( N=3, n=12), 0.356 for stomach cancer ( N=1, n=4) and 0.896 for breast cancer ( N=6, n=52, P75=3.602). When based on another commonly used ICER indicator, the median ratio of cost per quality-adjusted life-year gained to China′s per capita GDP (reported in 13 studies), the least cost was found in stomach cancer (0.495, N=3, n=8, P75=3.126), followed by esophageal cancer (0.960, N=1, n=4, P75=1.762) and breast cancer (2.056, N=9, n=64, P75=4.217). Data was not found for colorectal cancer. In addition, cost per cancer case detected was the most adopted indicator (32 studies). The median cost among all screening strategies for each cancer was 14 759 CNY for stomach cancer ( N=5, n=7), 49 680 CNY for colorectal cancer ( N=12, n=25) and 171 930 CNY for breast cancer ( N=13, n=24), respectively. Data was not available for esophageal cancer and rare for precancer cases detected. Evidence related to cost per disability-adjusted life-year gained was not available. Conclusions:At China′s national level and limited to the six cancers covered by the current study, the preliminary analysis suggests that stomach cancer and colorectal cancer were the most cost-effective target cancers and could be given priority in the future scaled-up screening in general populations. Esophageal cancer screening should be prioritized in high-risk areas. Breast cancer was also cost-effective in general but some of the intensive screening strategies were marginal. Data on liver cancer and lung cancer were too limited to conclude, and more well-designed studies and high-quality research evidence should be required. This priority ranking might be changed if other common cancers were involved analyses.

Objective:To investigate the protective effect and mechanism of dexamethasone in lung ischemia/reperfusion injury (LIRI) rats.Methods:① Part one experiment: 24 Sprague-Dawley (SD) rats were divided into four groups according to the random number method ( n = 6): standard ventilation group (N group), normal saline group (NS group), LIRI group, and dexamethasone+LIRI group (DEX group). The rat model of LIRI was established by clamping the left pulmonary hilum for 1 hour and reperfusing it for 2 hours. The DEX group was given dexamethasone 3 mg/kg 5 minutes before reperfusion, and NS group was injected with normal saline. Group N did not receive any treatment. The left lung tissue of the rats in each group were taken alive 2 hours after reperfusion. The lung tissue was harvested for lung wet/dry mass ratio (W/D) measurement. Hematoxylin-eosin (HE) staining and electron microscopy was used to observe the pathological changes of lung tissue and to assess the degree of injury. Ultrastructural changes of lung tissue were observed under electron microscope. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-6) in lung tissue were detected by enzyme linked immunosorbent assay (ELISA). The expressions of phosphorylated protein kinase B (p-AKT) was detected by Western Blot. ② Part two experiment: intervention with phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway inhibitor LY294002 to further explore the mechanism of dexamethasone in reducing lung injury induced by LIRI. Twenty-four SD rats were divided into four groups according to the random number method ( n = 6): N group, LIRI group, DEX group, and dexamethasone+LY294002+LIRI group (LY group). All the groups except the LY group were treated with membrane and intervention according to part one experiment. The LY group was injected with LY294002 0.3 mg/kg after injection of dexamethasone. The expressions of M1 macrophage polarization markers CD11c, CD16, and M2 macrophage polarization markers CD206, Arg1 were detected by immunohistochemistry. Results:① Part one experiment: compared with N group, the morphological and ultrastructural changes of lung tissue in the LIRI group were significantly changed, lung injury score, lung W/D ratio and TNF-α, IL-1β, IL-6 levels were significantly increased, and p-AKT expression was significantly decreased. Compared with the LIRI group, the morphological and ultrastructural changes of the lung tissue in the DEX group were significantly improved, and the lung injury score was reduced (5.00±0.89 vs. 8.83±0.75), lung W/D ratio and TNF-α, IL-1β, IL-6 levels were significantly decreased [lung W/D ratio: 6.25±0.56 vs. 8.27±0.72, TNF-α(ng/L): 93.28±16.42 vs. 205.90±25.30, IL-1β(ng/L): 130.10±10.81 vs. 209.10±19.20, IL-6 (ng/L): 195.80±21.17 vs. 310.50±20.77], p-AKT expression was significantly increased [p-AKT/AKT: (57.58±8.80)% vs. (36.62±9.25)%], and the differences were statistically significant (all P < 0.05). There was no significant difference in each index between NS group and N group. ② Part two experiment: compared with the N group, the expression of macrophage polarization markers CD11c, CD16, CD206 and Arg1 in the LIRI group were significantly increased. Compared with the LIRI group, the expressions of CD11c and CD16 in the lung tissue of the DEX group were significantly decreased, and the expressions of CD206 and Arg1 were significantly increased. The intervention of PI3K/AKT signaling pathway inhibitor LY294002 significantly blocked the effect of dexamethasone on LIRI-mediated macrophage polarization (CD11c immunohistochemical score: 7.20±0.36 vs. 5.00±0.34, CD16 immunohistochemical score: 8.20±0.48 vs. 7.40±0.64, CD206 immunohistochemical score: 5.80±0.59 vs. 7.40±0.28, Arg1 immunohistochemical score: 7.20±0.72 vs. 8.80±0.48, all P < 0.05). Conclusions:Dexamethasone pretreatment can alleviate the intrapulmonary inflammatory response and lung injury caused by LIRI in rats. The mechanism of action is related to the polarization direction of pulmonary macrophagesvia activation of the PI3K/AKT pathway by dexamethasone.

Objective:This study was to systematically update the economic evaluation evidence of colorectal cancer screening in mainland China.Methods:Based on a systematic review published in 2015, we expanded the scope of retrieval database (PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, CBM) and extended it to December 2018. Focusing on the evidence for nearly 10 years (2009-2018), basic characteristics and main results were extracted. Costs were discounted to 2017 using the consumer price index of medical and health care being provided to the residents, and the ratio of incremental cost-effectiveness ratio (ICER) to per capita GDP in corresponding years were calculated.Results:A total of 12 articles (8 new ones) were included, of which 9 were population-based (all cross-sectional studies) and 3 were model-based. Most of the initial screening age was 40 years (7 articles), and most of the frequency was once in a lifetime (11 articles). Technologies used for primary screening included: questionnaire assessment, immunological fecal occult blood test (iFOBT) and endoscopy. The most commonly used indicator was the cost per colorectal cancer detected, and the median (range) of the 20 screening schemes was 52 307 Chinese Yuan (12 967-3 769 801, n=20). The cost per adenoma detected was 9 220 Yuan (1 859-40 535, n=10). In 3 articles, the cost per life year saved (compared with noscreening) was mentioned and the ratio of ICER to GDP was 0.673 (-0.013-2.459, n=11), which was considered by WHO as "very cost-effective" ; The range of ratios overlapped greatly among different technologies and screening frequencies, but the initial age for screening seemed more cost-effective at the age of 50 years (0.002, -0.013-0.015, n=3), than at the 40 year-olds (0.781, 0.321-2.459, n=8). Conclusions:Results from the population-based studies showed that the cost per adenoma detected was only 1/6 of the cost per colorectal cancer detected, and limited ICER evidence suggested that screening for colorectal cancer was generally cost-effective in Chinese population. Despite the inconclusiveness of the optimal screening technology, the findings suggested that the initial screening might be more cost-effective at older age. No high-level evidence such as randomized controlled trial evaluation was found.