Detection of 14 sulfonate esters impurities of active pharmaceutical ingredients based on GC-MS/MS and LC-MS/MS / 药学学报

Two methods including gas chromatography tandem mass spectrometry (GC-MS/MS) and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) were established to detect common alkyl sulfonates and aryl sulfonates genotoxic impurities. Four alkyl sulfonates and methyl benzenesulfonate were determined by GC-MS/MS using butyl methanesulfonate as the internal standard, the chromatographic column was HP-5MS UI (30 mm × 0.25 mm, 0.25 µm), the carrier gas was helium, the flow rate was 1.0 mL·min-1 in a constant flow mode, the sample inlet temperature was set to 250 ℃, the split ratio was 10∶1, and the initial temperature of the heating program was 80 ℃, maintained for 1 minute, and then increased to 240 ℃ at a heating rate of 30 ℃·min-1 for 2 minutes. The mass spectrometry detector was an electron bombardment ion source (EI source), the data collection condition was multi reaction monitoring mode (MRM), and method validation using the raw material of clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of four alkyl sulfonates and methyl benzenesulfonate were good at 3-50 ng·mL-1 and 9-150 ng·mL-1, with a correlation coefficient of r > 0.999, The spiked recovery was 80%-120%. The detection limits were 1 and 3 ng·mL-1; Ten aryl sulfonates determined by LC-MS/MS, the chromatographic column was CSH Fluoro phenyl (100 mm × 2.1 mm, 1.7 µm), the mobile phase was methanol (B)-5 mmol·L-1 ammonium formate (D), with a flow rate of 0.2 mL·min-1, and gradient elution was performed. The gradient program (T/% B) was set as 0/20, 25/90, 35/90, 42/20. The mass spectrometer detector was electro spray ionization with positive ionization mode (ESI+), the data collection was in dynamic multi reaction monitoring mode (dMRM), and the method was validated using the raw material of the clinical drug citalopram hydrobromide as a sample. The results showed that the linear range of aryl sulfonates were good at 9-2 000 ng·mL-1, 3-100 ng·mL-1 and 0.9-30 ng·mL-1, respectively. The correlation coefficient r > 0.999, the spiked recovery was 80%-120%. The detection limits were 30, 1 and 0.3 ng·mL-1. Two detection methods did not detect potential sulfonate genotoxicity impurities in the above APIs. The established analytical methods are reliable and effective, which can provide reference for drug quality control and detection.

Growth retardation and its influencing factors in infants aged 0‒3 in Minhang District， Shanghai / 上海预防医学

ObjectiveTo investigate the detection rate and main influencing factors of growth retardation in infants aged 0-3 in Minhang District， and to provide relevant evidence for early intervention， nutrition promotion and health guidance in the future. MethodsFrom September 1， 2020 to August 31， 2021， the height， weight， basic information of parents， feeding methods， and lifestyle habits of infants who received systematic healthcare aged 0‒3 in community health service centers and Minhang maternal child health hospital were collected， and the current situation and influencing factors of infant growth retardation were analyzed. ResultsAmong the 68 637 infants who underwent a systematic physical examination in Minhang District， the total detection rate of growth retardation was 5.03% （3 453/68 637）. The detection rates in the 0-year-old， 1-year-old， 2-year-old， and 3-year-old groups were 6.57% （1 636/24 885）， 3.90% （664/17 031）， 4.62% （827/17 905）， and 3.72% （326/8 773）， respectively. There was no difference in the detection rate of growth retardation between boys and girls （P>0.05）， and a multinomial logistic regression analysis of 13 influencing factors （infant birth weight， birth length， parental weight， height， education level， mother’s childbearing age， delivery mode， household registration， feeding mode within 6 months， infant sleep， etc.） in univariate analysis showed that birth weight <2 500 g （OR=3.99， 95%CI： 2.809‒5.674） or ≥4 000 g （OR=12.78， 95%CI： 8.868‒18.443）， maternal height <150 cm （OR=7.10， 95%CI： 4.294‒11.753）， paternal height <160 cm （OR=5.65， 95%CI： 2.792‒11.422）， maternal education level of junior high school and below （OR=1.31， 95%CI： 1.087‒1.588）， paternal education level of junior high school and below （OR=1.02， 95%CI： 0.838‒1.236）， mixed feeding （OR=1.15， 95%CI： 1.031‒1.288）， and sleep duration exceeding the recommended time （OR=1.58， 95%CI： 1.466‒1.710） were risk factors for growth retardation in infants aged 0‒3. Infants with a birth length <50 cm or with household registration in Shanghai had a higher incidence of growth retardation. ConclusionGrowth retardation in infants aged 0‒3 is influenced by a combination of genetic， environmental， and sleep factors. It is essential for parents to realize the impact of growth retardation on the future of their children early on and actively participate in the early detection， screening， and intervention of growth retardation.

Etiological characteristics of viral gastroenteritis in pediatric inpatients under five years old in Shanghai， 2021‒2022 / 上海预防医学

ObjectiveTo investigate the changes in the pathogen spectrum of viral diarrhea in local pediatric inpatients as well as any variations in genotypes of major pathogens during the COVID-19 control period. MethodsFecal samples were collected from the children <5 years who were hospitalized due to acute gastroenteritis in a pediatric hospital in Shanghai. PCR test was carried out to detect rotavirus， norovirus， sapovirus， astrovirus and enteric adenovirus， and then genotyping was performed for major pathogens. ResultsOut of 546 samples， 37.55% tested positive for virus with the following positive rate ranking： norovirus GⅡ （22.16%）， group A rotavirus （16.12%）， astrovirus （2.93%）， enteric adenovirus （2.38%）， sapovirus （0.92%） and norovirus GⅠ （0.18%）. The predominant genotype within norovirus GⅡ were GⅡ.4［P31］ and GⅡ.4［P16］ with a proportion of 24.79% and 14.05% respectively. The detection rate of GⅡ.4［P31］ dropped significantly over the 2-year period （χ2＝16.140，P<0.001）. In addition， an emerging rotavirus genotype G8P ［8］， which was rarely found nationally， was discovered for the first time locally with an increasing proportion， accounting for 7.95% of all rotavirus positive cases. Phylogenic analysis demonstrated that the representative strains of this genotype were genetically closer to the DS-1-like G8P ［8］ strain found in Southeast Asia. ConclusionThe changes in the prevalence of various norovirus genotypes together with the emergence of rare rotavirus genotype in the local area illustrate the importance of continuous monitoring of viral diarrhea and genotyping of key pathogens. Increased local activity of the rare genotype also adds new parameters in the efficacy evaluation of marketed vaccines and development of potential new vaccines in near future.

Experience and Reflection on the Ethical Review of Organ Donation and Transplantation after Citizens’ Death in Medical Institution / 中国医学伦理学

In order to explore the ethical review experience of organ donation and transplantation after the death of citizens, and provide reference value for medical institutions to carry out corresponding ethical review. By using descriptive research, purpose sampling method and the principle of data saturation, 10 members and secretaries of ethics committee on clinical application of organ transplantation technology were finally selected as respondents for semi-structured interviews. The Colaizzi 7-step analysis method was adopted to analyze, summarize and refine the theme. The results showed that the ethical review experience of organ donation and transplantation after the death of citizens included four themes: the responsibilities of ethics committee, the key points of ethics review, the form of ethics review conference and its advantages and disadvantages, and the construction of the ethics committee of organ transplantation. Therefore, there are defects in the ethical review of organ donation and transplantation in medical institutions at present. These can be remedied by enriching elements of the ethical review following the four principles of medical ethics, refining the laws related to organ donation after citizens’ death, constructing a reasonable and efficient pattern of ethical review conference, and establishing a robust and appropriate operation mode of organ transplantation ethics committee.

Long-term auditory monitoring in children with Alport syndrome based on different degrees of renal injury / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.

The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise fatigue.@*METHODS@#A network pharmacological approach was used to explore potential mechanisms of action of Fructus lycii. Skeletal muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological analysis.@*RESULTS@#Six potential active components, namely quercetin, β-sitosterol, stigmasterol, 7-O-methylluteolin-6-C-beta-glucoside_qt, atropine, and glycitein, were identified to have potency in improving exercise fatigue via multiple pathways, such as the PI3K-Akt, neuroactive ligand-receptor interaction, IL-17, TNF, and MAPK signaling pathways. The immunofluorescence results indicated that quercetin, a significant active component in Fructus lycii, increased the mean staining area of 2-NBDG, TMRM, and MitoTracker, and decreased the area of CellRox compared to the control. Furthermore, the protein expression levels of p-38 MAPK, p-MAPK, p-JNK, p-PI3K, and p-AKT markedly increased after quercetin treatment.@*CONCLUSION@#Fructus lycii might alleviate exercise fatigue through multiple components and pathways. Among these, quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative stress. The PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

Proteomic analysis and validation of DNA repair regulation in the process of hepatocellular carcinoma recurrence / 临床肝胆病杂志

ObjectiveTo investigate the role and mechanism of DNA repair regulation in the process of hepatocellular carcinoma （HCC） recurrence. MethodsHCC tissue samples were collected from the patients with recurrence within two years or the patients with a good prognosis after 5 years， and the Tandem Mass Tag-labeled quantification proteomic study was used to analyze the differentially expressed proteins enriched in the four pathways of DNA replication， mismatch repair， base excision repair， and nucleotide excision repair， and the regulatory pathways and targets that play a key role in the process of HCC recurrence were analyzed to predict the possible regulatory mechanisms. The independent samples t-test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsFor the eukaryotic replication complex pathway， there were significant reductions in the protein expression levels of MCM2 （P=0.018）， MCM3 （P=0.047）， MCM4 （P=0.014）， MCM5 （P=0.008）， MCM6 （P=0.006）， MCM7 （P=0.007）， PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the nucleotide excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019）， RFC4 （P=0.002）， RFC5 （P<0.001）， and LIG1 （P=0.042）； for the base excision repair pathway， there were significant reductions in the protein expression levels of PCNA （P=0.019） and LIG1 （P=0.042） in the HCC recurrence group； for the mismatch repair pathway， there were significant reductions in the protein expression levels of MSH2 （P=0.026）， MSH6 （P=0.006）， RFC4 （P=0.002）， RFC5 （P<0.001）， PCNA （P=0.019）， and LIG1 （P=0.042） in recurrent HCC tissue. The differentially expressed proteins were involved in the important components of MCM complex， DNA polymerase complex， ligase LIG1， long patch base shear repair complex （long patch BER）， and DNA mismatch repair protein complex. The clinical sample validation analysis of important differentially expressed proteins regulated by DNA repair showed that except for MCM6 with a trend of reduction， the recurrence group also had significant reductions in the relative protein expression levels of MCM5 （P=0.008）， MCM7 （P=0.007）， RCF4 （P=0.002）， RCF5 （P<0.001）， and MSH6 （P=0.006）. ConclusionThere are significant reductions or deletions of multiple complex protein components in the process of DNA repair during HCC recurrence.

Role and possible mechanism of estrogen receptor α down-regulation leading to damage of TM4 Sertoli cell connectivity in mice / 中国药理学通报

Aim To investigate the role of autophagy in the dysfunction of testicular TM4 cell junction induced by ERα down-regulation. Methods TM4 cells were treated with different concentrations of E R a inhibitor ICI182780 (ICI), and the proliferative activity of TM4 cells was detected by CCK-8 method. The number and morphological changes of TM4 cells were observed by light microscope. The levels of E R a, junction function related proteins and autophagy marker proteins were detected by Western blot. The expression and localization of Cx43 were detected by immunofluorescence staining. The cells were treated with chloroquine (CQ) and ICI for 24 h. The expression levels of autophagy and junction function related proteins were detected by Western blot. Results When ICI concentration was 50 nmol • L ~ or above, the cell viability decreased significantly. The increase of cell vacuoles in ICI group was observed by light microscope. Compared with normal control group, the protein expression levels of E R a, ZO-1, occludin, claudin-11, p-catenin and Cx43 in ICI groups significantly dropped, while the expression levels of N-cadherin and E-cadherin had no significant changes; LC3 II significantly rose, while p62 expression significantly fell. The results of immunofluorescence showed that the fluorescence expression of Cx43 in ICI group decreased significantly, but the position of CX43 did not change significantly. Compared with ICI group, the expression levels of LC3 II, p62, Cx43, ZO-1 and β-Catenin significantly increased. Conclusions The down-regulation of E R a leads to damage of TM4 cell junction function, which may be related to the activation of autophagy.

Effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress / 中国药理学通报

Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplasmic reticulum stress. Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly, with six mice in each group. The mice in normal group or high-fat diet group were fed with regular or high-fat diet continuously for five months. The mice were weighed, anesthetized, and euthanized to collect testicular and epididymal tissue for analysis. The testicular tissue was weighed and their indices were calculated. Epididymal tissue was collected for semen analysis. The morphological alterations of testicular tissue were observed using hematoxylin-eosin ( HE ) staining. The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calculated. The expression levels of apoptosis and endoplasmic reticulum stress-related proteins in testicular tissue were detected by Western blot. The protein expression and localization of GRP78 in testicular tissue were further detected by immunofluorescence. Results The results showed that compared to the normal group, the high-fat diet group had a significant increase in body weight, a significant decrease in testicular index, sperm concentration, and sperm vability, loose arrangement of germ cells, significant thinning of the seminiferous epithelium, no significant change in the diameter of seminiferous tubules, a significant increase in germ cell apoptosis , with an increased apoptosis index, and significant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expression. The expression levels of GRP78 , p-IREl, XBP1, and ATF6a proteins were significantly up-regulated, while p-PERK, p-eIF2a, ATF4 protein expression showed no significant changes. Immunofluorescence results further showed a significant increase in the expression of GRP78 protein in the testicular tissue,with no significant changes in the expression location. Conclusions High-fat diet can induce the apoptosis of mouse testicular germ cells, and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.

Analysis of clinical effect and influencing factors of history-indicated cerclage or ultrasound-indicated cerclage in singleton pregnancy / 中华妇产科杂志

Objective: To investigate the clinical effect and the influencing factors of ultrasound-indicated cerclage and history-indicated cerclage in singleton gestation. Methods: The clinical data of 272 singleton pregnant women with cervical incompetence who underwent McDonald cervical cerclage due to medical history indication (history-indicated group) or ultrasound indication (ultrasound-indicated group) in Peking University First Hospital from January 2010 to February 2021 were retrospectively analyzed. The general clinical data and maternal and fetal outcomes were compared between the history-indicated group (141 cases) and ultrasound-indicated group (131 cases). According to the gestational age at delivery, 272 pregnant women who underwent cervical cerclage were further divided into ≥34 weeks group (225 cases) and <34 weeks group (47 cases), and the influencing factors of preterm birth before 34 weeks of gestation were analyzed. Results: (1) The median gestational age at cerclage was 16.6 weeks in the history-indicated group and 23.4 weeks in the ultrasound-indicated group, and the median gestational age extension at delivery was 21.4 weeks and 14.7 weeks, respectively, with statistically significant differences between the two groups (all P<0.05). (2) The full-term birth rate was 76.6% (108/141) in the history-indicated group and 71.0% (93/131) in the ultrasound-indicated group, the live birth rate was 97.2% (137/141) and 97.7% (128/131), and the median birth weight of live birth was 3 155 g and 3 055 g, respectively. The differences were not statistically significant (all P>0.05). Among 272 pregnant women with cervical cerclage, 265 neonates survived (97.4%, 265/272). The gestational age of 7 pregnant women who did not have live birth was ≤25 weeks of gestation (range: 19+1-25 weeks), and they were all clinically infected or confirmed chorioamnionitis or pathogenic microorganisms carrying during pregnancy, and their families gave up. The minimum birth weight of the surviving neonate was 850 g (gestational week of delivery was 26+6 weeks). (3) Univariate analysis showed that compared with ≥34 weeks group, the body mass index (BMI) of pregnant women in <34 weeks group was higher at 6-7 weeks of gestation (median: 24.5 vs 25.4 kg/m2), shorter cervical length (CL) at 1-2 weeks after surgery [(31.1±8.4) vs (26.1±11.0) mm], shorter CL at 26-28 weeks of gestation after surgery (median: 26.3 vs 16.0 mm), and higher incidence of elevated C-reactive protein (CRP) before and after surgery and before delivery. The differences were all statistically significant (all P<0.05). Multivariate logistic regression analysis showed that preterm birth before 34 weeks was negatively associated with CL at 26-28 weeks of gestation after cerclage (OR=0.902, 95%CI: 0.858-0.947; P<0.001), and was positively correlated with elevated CRP before delivery (OR=3.492, 95%CI: 1.652-7.381; P=0.001). There were no significant correlations between preterm birth and preoperative or postoperative CRP elevation, CL at 1-2 weeks after surgery, and BMI at 6-7 weeks of gestation (all P>0.05). Conclusions: Cervical cerclage for singleton pregnant women with cervical incompetence indicated by history or ultrasound both have good clinical efficacy, and there is no significant difference in maternal and fetal outcomes between the two groups. CL at 26-28 weeks of gestation and CRP before delivery are risk factors for preterm birth before 34 weeks of gestation after cervical cerclage.

Comparison of BCR::ABL (P210) mRNA levels detected by dPCR and qPCR methods in patients with chronic myeloid leukemia / 中华血液学杂志

Objective: To compare digital polymerase chain reaction (dPCR) and real-time quantitative PCR (qPCR) measurements of BCR::ABL (P210) mRNA expression in patients with chronic myeloid leukemia (CML) . Methods: In this non-interventional, cross-sectional study, BCR::ABL (P210) mRNA was simultaneously measured by dPCR and qPCR in peripheral blood samples collected from patients with CML who underwent tyrosine kinase inhibitor therapy and who achieved at least a complete cytogenetic response from September 2021 to February 2023 at Peking University People's Hospital. The difference, correlation, and agreement between the two methods were evaluated using the Wilcoxon signed-rank test, Spearman's correlation, and Bland-Altman analysis, respectively. Results: In total, 459 data pairs for BCR::ABL mRNA expression measured by dPCR and qPCR from 356 patients with CML were analyzed. There was a significant difference in BCR::ABL mRNA expression between the two methods (P<0.001). When analyzed by the depth of the molecular response (MR), a significant difference only existed for patients with ≥MR4.5 (P<0.001). No significant difference was observed for those who did not achieve a major MR (no MMR; P=0.922) or for those who achieved a major MR (MMR; P=0.723) or MR4 (P=0.099). There was a moderate correlation between the BCR::ABL mRNA expression between the two methods (r=0.761, P<0.001). However, the correlation gradually weakened or disappeared as the depth of the MR increased (no MMR: r=0.929, P<0.001; MMR: r=0.815, P<0.001; MR4: r=0.408, P<0.001; MR4.5: r=0.176, P=0.176). In addition, the agreement in BCR::ABL mRNA expression between the two methods in those with MR4.5 was weaker than other groups (no MMR: ▉= 0.042, P=0.846; MMR:▉=0.054, P=0.229; MR4:▉=-0.020, P=0.399; MR4.5:▉=-0.219, P<0.001) . Conclusions: dPCR is more accurate than qPCR for measuring BCR::ABL (P210) mRNA expression in patients with CML who achieve a stable deep MR.

Advanced subunit vaccine delivery technologies: From vaccine cascade obstacles to design strategies

Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.

Epidemiological characteristics and influencing factors of nosocomial Escherichia coli infection in children / 公共卫生与预防医学

Objective To analyze the epidemiological characteristics of nosocomial Escherichia coli infection and risk factors of ESBLs-producing Escherichia coli infection in children, and to provide scientific basis for better prevention of nosocomial Escherichia coli infection in children. Methods A total of 169 children with nosocomial infection hospitalized in Handan Regional Children's Hospital from January 2020 to December 2020 were selected by random sampling method. After specimen collection, bacteria were identified by VitEK-32 identification system , and drug sensitivity of isolated pure Escherichia coli colony was identified by automatic drug sensitivity analyzer Phoenix 100. Statistical analysis of drug resistance of Escherichia coli. The clinical data of the children were retrieved from the case system by uniformly trained professionals, and the department distribution, underlying diseases, clinical characteristics, antibiotic resistance, length of hospital stay, surgery, invasive exercises and other clinical data of all the children were counted. Factor logistic regression analysis of the risk factors of nosocomial infection of ESBLs Escherichia coli in children in the hospital. Results A among of 39 strains of Escherichia coli were detected in children with nosocomial infection in children's hospital. The main specimens were 22 strains (56.41%) in sputum, 11 strains (28.21%) in urine and 6 strains (15.38%) in blood.Twenty-one strains of ESBLs Escherichia coli were detected, with a positive rate of 53.85%. Fever was the most common first symptom in 37 cases (94.87%). Children with ESBLs (+) Escherichia coli infection were significantly higher than those with ESBLs (-) Escherichia coli in age, length of hospitalization, neonates/recent use of broad-spectrum antibiotics, complicated underlying diseases, and invasive operation (P<0.05). Multivariate logistic regression analysis showed that recent use of antibiotics, combined with underlying diseases, and invasive operation were independent risk factors for ESBLs infection in children in hospital (P<0.05). Conclusion The incidence of nosocomial Escherichia coli infection in children is high, and active intervention should be carried out for children who have recently used antibiotics, complicated with underlying diseases, and invasive operations to reduce the risk of ESBLs Escherichia coli infection.

Rapamycin mediated caspase 9 homodimerization to safeguard human pluripotent stem cell therapy / 生物工程学报

Human induced pluripotent stem cells (hiPSCs) are promising in regenerative medicine. However, the pluripotent stem cells (PSCs) may form clumps of cancerous tissue, which is a major safety concern in PSCs therapies. Rapamycin is a safe and widely used immunosuppressive pharmaceutical that acts through heterodimerization of the FKBP12 and FRB fragment. Here, we aimed to insert a rapamycin inducible caspase 9 (riC9) gene in a safe harbor AAVS1 site to safeguard hiPSCs therapy by drug induced homodimerization. The donor vector containing an EF1α promoter, a FRB-FKBP-Caspase 9 (CARD domain) fusion protein and a puromycin resistant gene was constructed and co-transfected with sgRNA/Cas9 vector into hiPSCs. After one to two weeks screening with puromycin, single clones were collected for genotype and phenotype analysis. Finally, rapamycin was used to induce the homodimerization of caspase 9 to activate the apoptosis of the engineered cells. After transfection of hiPSCs followed by puromycin screening, five cell clones were collected. Genome amplification and sequencing showed that the donor DNA has been precisely knocked out at the endogenous AAVS1 site. The engineered hiPSCs showed normal pluripotency and proliferative capacity. Rapamycin induced caspase 9 activation, which led to the apoptosis of all engineered hiPSCs and its differentiated cells with different sensitivity to drugs. In conclusion, we generated a rapamycin-controllable hiPSCs survival by homodimerization of caspase 9 to turn on cell apoptosis. It provides a new strategy to guarantee the safety of the hiPSCs therapy.

Decolorization and biodegradation of acid orange 7 by white-rot fungi / 生物工程学报

Azo dyes are widely used in textile, paper and packing industries, and have become one of the research hot spots in dye wastewater treatment because of their carcinogenicity, teratogenic mutagenicity, stable structure and degradation difficulty. In this study, the biodecolorization of acid orange 7 (AO7), an azo dye, by different white rot fungi was investigated, and the effect of different conditions on the decolorization rate of the dye was analyzed. At the same time, the degradation liquor was analyzed and the phytotoxicity experiment was performed to deduce the possible degradation pathway of AO7 and assess the toxicity of its degradation products. The results showed that the decolorization rate reached 93.46% in 24 h at pH 4.5, 28 ℃ by Pleurotus eryngii and Trametes versicolor when AO7 concentration was 100 mg/L. The biodegradation pathway of AO7 was initiated by the cleavage of the azo bond of AO7, generating p-aminobenzenesulfonic acid and 1-amino-2-naphthol. Subsequently, the sulfonic acid group of p-aminobenzene sulfonic acid was removed to generate hydroquinone. Moreover, the 1-amino-2-naphthol was de-ringed to generate phthalic acid and p-hydroxybenzaldehyde, and then further degraded into benzoic acid. Finally, hydroquinone and benzoic acid may be further oxidized into other small molecules, carbon dioxide and water. Phytotoxicity experiment showed that the toxicity of AO7 could be reduced by P. eryngii and T. versicolor.

Ethics Considerations on Public Management of Disaster Rescue under the Context of Epidemic Prevention and Control / 中国医学伦理学

Natural disasters and epidemics are intertwined, posing a great threat to national health and property security, and hindering economic development. Faced with the complex rescue environment, the contradiction between individual interests and collective interests may escalate, causing ethical dilemmas different from those encountered in conventional medicine. In the context of COVID-19 epidemic prevention and control, how to maximize the coordination of the conflict between individual interests and collective interests, minimize the losses caused by disasters, and maintain social stability is a new topic of ethical research. Based on the ethical principles of public management, this paper explored the ethical conflicts of public management faced by emergency disaster rescue, in the view of providing ethical theoretical support for dealing with the practical difficulties of emergency public health crisis, and promoting the development and progress of disaster medical rescue work.

Enlightenment on the Ideological Connotation of Spirit of Great Physician to Contemporary Medical Ethics Construction / 中国医学伦理学

Spirit of Great Physician, puts forward relevant requirements on the moral standards and humanistic qualities that doctors should possess. By tracing the formation background of Spirit of Great Physician, analyzing its rich ideological connotation, reflecting on the needs of contemporary society for medical ethics on the basis of the medical ethics standard of Spirit of Great Physician, combining the background of social development and medical reform in the new era, as well as the moral dilemma in the medical environment, this paper proposed that contemporary society should take the combination of the internal requirements of "moral self-discipline" and the external constraints of "moral heteronomy" as the new path of medical ethics construction. The purpose of this study was to provide theoretical reference for improving the construction system of contemporary medical ethics, enhancing the moral character of medical staff and building a good medical environment.

Effect of cognitive behavioral therapy on quality of life in patients with Parkinson's disease： a Meta-analysis / 四川精神卫生

BackgroundDepression， anxiety， impulse control disorders， insomnia are prevalent non-motor symptoms of Parkinson's disease， severely impairing the quality of life of patients. Cognitive behavioral therapy （CBT） is a common psychological intervention for various clinical psychological conditions， which can improve anxiety， insomnia and depression in patients with Parkinson's disease. However， the current research evidence on the effects of CBT in improving quality of life in patients with Parkinson's disease remains inconsistent. ObjectiveTo assess the effects of CBT on the quality of life among patients with Parkinson's disease， so as to provide references for the clinical application of CBT in this population. MethodsOn May 25， 2023， a systematic search was conducted across PubMed， PsycINFO， Embase， CNKI， Wanfang Database and VIP Database to identify randomized controlled trials investigating the impact of CBT on the quality of life in patients with Parkinson's disease. Literature screening， quality evaluation and data extraction were performed， focusing on variables related to quality of life， anxiety， and depression. Meta-analysis was performed using Stata 13.0 and RevMan 5.3. ResultsA total of 11 studies with 456 participants were included， comprising 241 in the CBT group and 215 in the control group. The CBT group exhibited significantly higher quality of life compared with the control group （SMD=0.47， 95% CI： 0.27~0.67， P<0.01）. Anxiety and depression scores in CBT group were significantly lower than those in the control group （SMD=-0.63，95% CI：-0.84~-0.43， P<0.01； SMD=-0.83， 95% CI： -1.15~-0.51， P<0.01）. Among the 11 studies， 6 studies delivered CBT remotely and 5 studies implemented CBT face-to-face. Meta-analysis results revealed that remote CBT group yielded significantly higher quality of life （SMD=0.43， 95% CI： 0.17~0.70， P<0.01）， and lower anxiety and depression scores （SMD=-0.62， 95% CI： -0.91~-0.34， P<0.01； SMD=-0.78， 95% CI： -1.34~-0.21， P<0.01） compared with the control group. Similarly， face-to-face CBT group showed better outcomes than the control group in terms of quality of life， anxiety and depression （SMD=0.51， 95% CI： 0.22~0.81， P<0.01； SMD=-0.64， 95% CI： -0.93~-0.35， P<0.01； SMD=-0.90， 95% CI： -1.20~-0.60， P<0.01）. ConclusionCBT may contribute to alleviating anxiety and depression levels of patients with Parkinson's disease， and improving their quality of life.｛Funded by Shanghai 13th Five-Year Key Specialty Construction Project （number， shslczdzk04901）； Nature Fund Project of Shanghai Science and Technology Commission （number， 22ZR1459300）； Shanghai Municipal Health Commission Traditional Chinese Medical Science Non-drug Therapy Demonstration Center Project ［number， ZY（2021-2023） -0204-03］｝

Evaluation of the Short-Term Efficacy and Safety of Orelabrutinib Combined with High-Dose Methotrexate in the First-line Treatment of Elderly Patients with High Risk Primary Central Nervous System Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients.@*METHODS@#Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP).@*RESULTS@#The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05).@*CONCLUSION@#For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.

The Value of VR-PVEP in Objective Evaluation of Monocular Refractive Visual Impairment / 法医学杂志

OBJECTIVES@#To study the virtual reality-pattern visual evoked potential (VR-PVEP) P100 waveform characteristics of monocular visual impairment with different impaired degrees under simultaneous binocular perception and monocular stimulations.@*METHODS@#A total of 55 young volunteers with normal vision (using decimal recording method, far vision ≥0.8 and near vision ≥0.5) were selected to simulate three groups of monocular refractive visual impairment by interpolation method. The sum of near and far vision ≤0.2 was Group A, the severe visual impairment group; the sum of near and far vision <0.8 was Group B, the moderate visual impairment group; and the sum of near and far vision ≥0.8 was Group C, the mild visual impairment group. The volunteers' binocular normal visions were set as the control group. The VR-PVEP P100 peak times measured by simultaneous binocular perception and monocular stimulation were compared at four spatial frequencies 16×16, 24×24, 32×32 and 64×64.@*RESULTS@#In Group A, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 24×24, 32×32 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group B, the differences between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at 16×16, 24×24 and 64×64 spatial frequencies were statistically significant (P<0.05); and the P100 peak time of normal vision eyes at 64×64 spatial frequency was significantly different from the simulant visual impairment eyes (P<0.05). In Group C, there was no significant difference between P100 peak times of simulant visual impairment eyes and simultaneous binocular perception at all spatial frequencies (P>0.05). There was no significant difference in the P100 peak times measured at all spatial frequencies between simulant visual impairment eyes and simultaneous binocular perception in the control group (P>0.05).@*CONCLUSIONS@#VR-PVEP can be used for visual acuity evaluation of patients with severe and moderate monocular visual impairment, which can reflect the visual impairment degree caused by ametropia. VR-PVEP has application value in the objective evaluation of visual function and forensic clinical identification.