Tumor-targeted metabolic inhibitor prodrug labelled with cyanine dyes enhances immunoprevention of lung cancer

Recent progress in targeted metabolic therapy of cancer has been limited by the considerable toxicity associated with such drugs. To address this challenge, we developed a smart theranostic prodrug system that combines a fluorophore and an anticancer drug, specifically 6-diazo-5-oxo-l-norleucine (DON), using a thioketal linkage (TK). This system enables imaging, chemotherapy, photodynamic therapy, and on-demand drug release upon radiation exposure. The optimized prodrug, DON-TK-BM3, incorporating cyanine dyes as the fluorophore, displayed potent reactive oxygen species release and efficient tumor cell killing. Unlike the parent drug DON, DON-TK-BM3 exhibited no toxicity toward normal cells. Moreover, DON-TK-BM3 demonstrated high tumor accumulation and reduced side effects, including gastrointestinal toxicity, in mice. This study provides a practical strategy for designing prodrugs of metabolic inhibitors with significant toxicity stemming from their lack of tissue selectivity.

Clinical features of critically ill pregnant and parturient women infected with chronic hepatitis B virus： An analysis of 41 cases / 临床肝胆病杂志

ObjectiveTo investigate the clinical features and outcomes of critically ill pregnant and parturient women with chronic hepatitis B virus （HBV） infection， and to provide clinical experience for the rescue of critically ill pregnant and parturient women and the prevention and treatment of the severe exacerbation of liver disease. MethodsA total of 41 pregnant and parturient women with chronic HBV infection who were admitted to Department of Critical Care Medicine， Nanjing Second Hospital， from March 2013 to March 2023 were enrolled in this study， and their clinical data were collected through the electronic medical record system of hospital to summarize the main causes of transfer to the intensive care unit （ICU）， the causes of death， and treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The chi-square test was used for comparison of categorical data between two groups. ResultsAmong the 41 patients， 13 （31.71%） did not receive regular antenatal examination and 8 （19.51%） with a high viral load （HBV DNA ≥2×105 IU/mL） did not receive antiviral therapy. Cesarean section was the main mode of delivery in 32 patients （78.05%）； 23 patients （56.10%） had premature delivery， and 5 patients died （12.20%）. The top three causes of transfer to the ICU were liver failure， postpartum hemorrhage， and hypertensive disorders of pregnancy. Liver failure mainly occurred in late pregnancy， with hepatic encephalopathy as the most common complication （28.57%） and intrahepatic cholestasis of pregnancy as the most common comorbidity （21.43%）； among the 14 patients with liver failure， 6 （42.86%） received regular antenatal examination， and 13 （92.86%） did not receive antiviral therapy before admission. The mean length of ICU stay was 3.31±1.65 days for the patients with postpartum hemorrhage， among whom the patients with severe liver disease had coagulation disorders before delivery， which were difficult to correct after 48 hours of treatment. ConclusionPregnant and parturient women with chronic HBV infection tend to have complex conditions and a relatively high mortality rate. For pregnant and parturient women with chronic HBV infection， assessment of liver status， regular antenatal examination， and timely antiviral therapy are of vital importance to reduce severe exacerbation and mortality rate.

Sex differences in cardiovascular health among children aged 6-8 years in Beijing City / 中国学校卫生

Objective@#To explore sex difference in the cardiovascular health (CVH) status of 6-8 year old children in Beijing, so as to inform the early intervention of CVH related lifestyles.@*Methods@#Based on the Beijing Children s Growth and Health Cohort (PROC), baseline physical examination, sequential questionnaire survey, and laboratory tests were conducted among 1 914 grade 1 students. Children s CVH and its subscales (health behaviors and health factors) scores were calculated according to the Life s Essential 8 (LE 8) index and categorized into high, moderate, and low CVH. CVH scores were reported as medians and interquartile ranges; sex differences were compared using the Chi square test and Wilcoxon test.@*Results@#Among the 1 914 participants, the percentages of high, moderate, and low CVH were 35.7%, 63.5%, and 0.8%, respectively, and the percentages of high, moderate, and low health behavior scores were 25.9%, 67.5%, and 6.6%, respectively, with no statistically significant differences between sex ( χ 2=2.30, 0.07, P >0.05). The rates of high, moderate, and low health factor scores for boys and girls were 61.1%, 36.0%, 2.9% and 71.1%, 28.4%, 0.5%, respectively, with a statistically significant sex difference ( χ 2=31.88, P < 0.01). The overall CVH score was 76.0(70.0, 83.0), 76.0(69.0, 82.0) for boys, and 77.0(71.0, 83.0) for girls. Among the health behavior metrics, sleep scores were the best and physical activity scores were the worst[100.0(90.0,100.0), 40.0(20.0, 80.0 )]; among the health factor metrics, blood glucose scores were the best and lipid scores were the worst[100.0(100.0,100.0), 60.0(40.0,100.0)]. In respect to health factors, there were significant gender differences in body mass index, blood lipids, blood sugar, and blood pressure scores ( Z =-6.92, 3.01, -6.60, -2.30, <0.05), but there were no significant gender differences in diet, physical activity, nicotine exposure, or sleep scores with regards to health behaviors ( Z =0.99, 0.88, -0.13, 0.36, P > 0.05 ). Compared to boys, girls in the low and moderate CVH groups had high health factor scores despite low health behavior scores.@*Conclusion@#Most 6 to 8-year-old children in Beijing were found to have relatively good CVH, and optimization of children s CVH status can be achieved by promoting healthier lifestyles and monitoring health factors, especially among boys.

Identification of mixed medicinal powder of Epimedii Folium with different origins based on pyrosequencing technology / 药学学报

There are many multi-original medicinal materials in Chinese Pharmacopoeia, and the mixed use of medicinal materials from different sources is common, which has certain influence on the stability of clinical medication. In this study, pyrosequencing technology was used to screen species-specific single nucleotide polymorphisms (SNP) from commonly used DNA barcode sequences, and a rapid and accurate molecular identification method for original species in mixed medicinal powder of Epimedii Folium was established. Multiple sequence alignment analysis showed that the 176th (C/T) mutation and the 196th (A/G) mutation of ITS, the 123rd (C/G) mutation of matK and the 892nd (A/C) mutation of rbcL could be used as the unique SNPs of E. sagittatum, E. koreanum, E. brevicornu and E. pubescens, respectively. In this study, the applicability of pyrosequencing and Sanger sequencing methods in the sequencing of mixture samples was investigated from the perspective of sensitivity and stability. Pyrosequencing method has higher detection sensitivity than Sanger sequencing method for low content samples in the mixed samples. Stability analysis showed that pyrosequencing technology could still obtain effective sequencing results for the amplified products of template DNA after 45 min of 95 ℃ high temperature water bath, while the critical point of Sanger sequencing method was 30 min. In this study, a new identification technology of Epimedii Folium mixed powder primordial species based on pyrosequencing and specific SNP was developed, which can quickly and accurately identify the mixed use of Epimedii Folium with high sensitivity and stability, and can also support the identification of different primordial species and mixed powder primordial herbs, which is conducive to ensuring the consistency and stability of clinical medication.

Toxic Epidermal Necrolysis Induced by Sintilimab: A Case Report

Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe.We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.

Network Pharmacology and Experimental Validation to Explore Mechanism of Tetrahydropalmatine on Acute Myocardial Ischemia / 中国结合医学杂志

OBJECTIVE@#To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI).@*METHODS@#First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro.@*RESULTS@#MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model.@*CONCLUSIONS@#THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones.

Catheter ablation versus medical therapy for atrial fibrillation with prior stroke history: a prospective propensity score-matched cohort study / 老年心脏病学杂志（英文版）

BACKGROUND@#Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients.@*METHODS@#AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE.@*RESULTS@#During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants.@*CONCLUSIONS@#In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Methyl ferulic acid ameliorates ethanol-induced L02 cell steatosis through microRNA-378b-mediated CaMKK2-AMPK pathway / 中国中药杂志

Alcoholic liver disease(ALD), with its increasing morbidity and mortality, has seriously and extensively affected the health of people worldwide. Methyl ferulic acid(MFA) has been proven to significantly inhibit alcohol-induced lipid production in L02 cells through the AMP-activated protein kinase(AMPK) pathway, but its in-depth mechanism remains unclear. This study aimed to further clarify the mechanism of MFA in improving lipid accumulation in L02 cells through the microRNA-378b(miR-378b)-mediated calcium/calmodulin-dependent protein kinase kinase 2(CaMKK2)-AMPK signaling pathway based on existing researches. L02 cells were induced by 100 mmol·L~(-1) ethanol for 48 h to establish the model of ALD in vitro, and 100, 50, and 25 μmol·L~(-1) concentration of MFA was treated. MiR-378b plasmids(containing the overexpression plasmid-miR-378b mimics, silence plasmid-miR-378b inhibitor, and their respective negative control-miR-378b NCs) were transfected into L02 cells by electroporation to up-regulate or down-regulate the levels of miR-378b in L02 cells. The levels of total cholesterol(TC) and triglyceride(TG) in cells were detected by commercial diagnostic kits and automatic biochemical analyzers. The expression levels of miR-378b in L02 cells were detected by real-time quantitative polymerase chain reaction(qRT-PCR). CaMKK2 mRNA levels were detected by PCR, and protein expressions of related factors involved in lipid synthesis, decomposition, and transport in lipid metabolism were detected by Western blot. The results displayed that ethanol significantly increased TG and TC levels in L02 cells, while MFA decreased TG and TC levels. Ethanol up-regulated the miR-378b level, while MFA effectively inhibited the miR-378b level. The overexpression of miR-378b led to lipid accumulation in ethanol-induced L02 cells, while the silence of miR-378b improved the lipid deposition induced by ethanol. MFA activated the CaMKK2-AMPK signaling pathway by lowering miR-378b, thus improving lipid synthesis, decomposition, and transport, which improved lipid deposition in L02 cells. This study shows that MFA improves lipid deposition in L02 cells by regulating the CaMKK2-AMPK pathway through miR-378b.

Meta-analysis of acupuncture-moxibustion treatment of overactive bladder in adults in the past decade / 针灸推拿医学（英文版）

Objective: To systematically assess the effectiveness and safety of using acupuncture-moxibustion therapy alone to treat adult overactive bladder (OAB) by taking oral Western medication solely as the control, and to provide evidence-based reference for acupuncture-moxibustion treatment of OAB. Methods: A systemic search was conducted through China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), PubMed, Cochrane Library, and Excerpta Medica Database (EMBASE). RevMan 5.3 was used for meta-analysis. Statistical descriptions were made using standardized mean difference (SMD), confidence interval (CI), and risk ratio (RR). Results: Eight randomized controlled studies were finally recruited and were analyzed after being grouped according to intervention methods. Regarding urinary symptoms, compared with sole use of oral Western medication, acupuncture plus moxibustion can more effectively reduce 24 h urinary frequency [P=0.01, SMD=-0.57, 95％CI (-1.02, -0.12)], 24 h nocturia frequency [P=0.03, SMD=0.49, 95％CI (0.05, 0.94)], and OAB syndrome score (OABSS) [P<0.001, SMD=-3.67, 95％CI (-4.48, -2.86)]. Acupuncture combined with moxibustion and oral Western medication work equivalently in comparing 24 h urinary urgency frequency [P=0.38, SMD=-0.17, 95％CI (-0.57, 0.22)], 24 h urgent incontinence frequency [P=0.25, SMD=0.26, 95％CI (-0.18, 0.70)], and single voiding volume [P=0.22, SMD=1.15, 95％CI (-0.70, 3.00)]. There were no significant differences between acupuncture/electroacupuncture and oral medication in comparing 24 h urinary frequency [P=0.46, SMD=0.07, 95％CI (-0.12, 0.26)], 24 h urinary urgency frequency [P=0.18, SMD=0.70, 95％CI (-1.71, 0.32)], 24 h nocturia frequency [P=0.46, SMD=-0.71, 95％CI (-2.60, 1.17)], 24 h urgent incontinence frequency [P=0.08, SMD=-0.22, 95％CI (-0.48, 0.03)], single voiding volume [P=0.09, SMD=0.17, 95％CI (-0.02, 0.36)], or OABSS [P=0.96, SMD=-0.07, 95％CI (-2.65, 2.52)]. Compared with oral Western medication, moxibustion can more effectively reduce 24 h urinary frequency [P<0.001, SMD=-6.53, 95％CI (-7.65, -5.44)] and 24 h urinary urgency frequency [P<0.001, SMD=-1.6, 95％CI (-2.85, -0.36)]. In comparing the adverse reaction rate, acupuncture-moxibustion was associated with a lower rate compared with oral medication [P=0.002, RR=0.07, 95％CI (0.01, 0.37)], but the difference was statistically insignificant between acupuncture/electroacupuncture and oral medication [P=0.40, RR=0.57, 95％CI (0.16, 2.12)]. Conclusion: Acupuncture-moxibustion is equivalent to the sole use of oral Western medication in improving urinary symptoms in OAB patients and has a higher safety rating.

Non-targeted LC-MS profiling reveals association between human early embryo grades and levels of amino acids and carnitines in embryo culture medium / 中华检验医学杂志

Objective:In order to determine the development potential of human embryos in vitro, amino acid and carnitine levels were measured in the culture medium of different grades of early human embryos. Methods:From the infertile couples who received in vitro fertilization-embryo transfer treatment in the Department of Reproductive Medicine of Linyi People′s Hospital from June 2022 to December 2022, the age of the women was defined as 25-35 years old [31.5(26.5, 33.25)] with 8-20 eggs, 126 cultured cells and embryos of the third day were randomly collected from infertile couples. They were divided into three groups according to the morphological level of the corresponding embryos: excellent, neutral and poor. Amino acids and L-carnitines levels in culture medium were detected by liquid chromatography-mass spectrometry (LC-MS). Using analysis of variance to compare differences among groups, correlation analysis, factor analysis was performed to analyze the association between the levels of amino acids and L-carnitines and development potential of early human embryos.Results:The value of Methionine/Phenylalanine was found statistically different among superior embryo (3.09±1.67), moderate embryo (4.00±1.19) and inferior embryo (4.99±2.04). The difference between the three groups was statistically different ( F=7.09, P<0.05): superior embryo vs moderate embryo ( t=-0.91, P<0.05), superior embryo vs inferior embryo ( t=-1.91, P<0.05), moderate embryo vs inferior embryo ( t=-0.99, P<0.05). Among different amino acids, Phe had the strongest positive correlation with Tyr ( r=0.99, P<0.01). Among different carnitines, C 8/C 10 has the strongest positive correlation with C 5DC+C 6OH/C 16( r=0.44, P<0.01). The weight value of leucine (isoleucine), arginine, valine/phenylalanine, glycine, tyrosine and carnitine(C 5DC+C 6OH)/C 8 calculated by the least square fitting model is 2.22, 1.99, 1.65, 1.54, 1.21 and 1.15 respectively. Conclusion:Leucine, arginine, valine/phenylalanine, glycine, tyrosine and carnitine (C 5DC+C 6OH)/C 8 in embryo culture medium were significantly correlated with the levels of early human embryos in vitro.

A case of amniotic band syndrome after fetal reduction by radiofrequency ablation / 中华围产医学杂志

This article reported a survived case of amniotic band syndrome (ABS) following fetal reduction by radiofrequency ablation. The woman conceived monochorionic diamniotic twin pregnancy spontaneously. Prenatal ultrasound at 24 weeks of gestation indicated twin-twin transfusion syndrome (stage Ⅲ), and radiofrequency ablation for fetal reduction was successfully performed after formal consent. At 28 +6 weeks, ultrasound reexamination revealed significant edema in the left foot of the fetus, with banding around the ankle, as well as the strangulation mark and narrowing rings. Fetal ABS (ⅡB stage) was diagnosed after multidisciplinary consultation. An immediate emergency cesarean section was performed and a live male baby was born. A thin amniotic band could be seen wrapping around the left ankle of the newborn for several rounds, with obvious strangulation marks about 1 cm deep into the skin, and significant edema on the dorsum and sole of the foot, and the submalleolus area. The amniotic band was released at once, and the edema faded gradually after surgery. After a follow-up of 28 days, the lower limbs of the newborn became normal.

The influence of serum triggering receptor expressed on myeloid cells 1 level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome / 中华老年医学杂志

Objective:To study the influence of serum triggering receptor expressed on myeloid cells 1(TREM-1)level on prognosis in elderly patients with sepsis and acute respiratory distress syndrome(ARDS).Methods:A total of 100 elderly patients with sepsis were selected as the research objects.All the patients with sepsis were divided into sepsis ARDS group and sepsis non-ARDS group.General data and TREM-1 level were compared between the two groups.The patients with sepsis ARDS were divided into death group and survival group according to the survival status during the 28-day follow-up.TREM-1 level, acute physiology and chronic health evaluation(APACHE)Ⅱ score and SOFA score were compared between the two groups.The correlation between serum TREM-1 level and procalcitonin(PCT), APACHE Ⅱ score and SOFA score was analyzed.The survival rate of high TREM-1 level group and low TREM-1 level group was compared.Results:The age, white blood cell(WBC), PCT, APACHE Ⅱ score, SOFA score and TREM-1 level of sepsis ARDS patients were significantly higher than those of non-ARDS patients( t=2.722, 6.088, 11.55, 6.889, 4.661, 6.122, all P<0.05). The incidence of sepsis ARDS patients with chronic obstructive pulmonary disease was significantly higher than that of non-ARDS patients( χ2=7.895, P<0.05). Serum TREM-1 level, APACHE Ⅱ score and SOFA score of ARDS patients in death group were significantly higher than those in survival group( t=3.293, 6.173, 4.255, all P<0.05). Serum TREM-1 level was positively correlated with PCT, APACHE Ⅱ score and SOFA score( t=0.553, 0.602, 0.636, P<0.001). The Kaplan-Meier survival curve showed that the survival rate of high TREM-1 level group was significantly lower than that of low TREM-1 level group( χ2=3.999, P=0.036). Cox regression analysis showed that TREM-1 level was a risk factor for the prognosis of ARDS patients with sepsis( HR=1.893, 95% CI: 1.049-3.414). Conclusions:Serum TREM-1 level is significantly increased in elderly patients with sepsis ARDS, which is closely related to the prognosis and can be used as a potential prognostic biomarker.

The effect of Helicobacter pylori eradication on development of metachronous gastric cancer after endoscopic submucosal dissection of elderly patients with early gastric cancer / 中华老年医学杂志

Objective:To explore the effect of Helicobacter pylori(HP)eradication on development of metachronous gastric cancer(MGC)after endoscopic submucosal dissection(ESD)in elderly patients with early gastric cancer.Methods:From January 2014 to December 2019, 748 early gastric cancer patients aged 60 years or older, receiving ESD in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, were included.According to the situation of HP infection and eradication efficacy within 1 year postoperatively, patients were divided into three groups.The patients with HP infection and successful HP-eradication were enrolled into successful eradication group, those without eradicating or with eradication failure were enrolled into eradication failure group, those with HP negative were enrolled into HP-negative group.And then the occurrence and risk factors of MGC after ESD among the three groups were statistically analyzed.Results:MGC were detected in 58 cases(7.7%)in elderly patients with early gastric cancer after ESD.The median follow-up time was 39 months.The multivariate regression analysis results of MGC showed that no HP-eradication or HP eradication of failure( HR=2.231, 95% CI: 1.054-4.722, P=0.036)and multiple lesions( HR=1.857, 95% CI: 1.076-3.204, P=0.026)were independent risk factors.Non-smoking was a protective factor for the occurrence of MGC( HR=0.409, 95% CI: 0.234-0.716, P=0.002). After adjusting for confounding factors, Cox proportional risk regression analysis showed that the incidence of MGC was significantly higher in group of no HP-eradicating or HP-eradicating of failure than in group of successful HP-eradicating group( χ2=37.877, P<0.001). Conclusions:HP eradication can effectively prevent MGC in elderly patients with early gastric cancer after ESD.Multiple lesions and smoking are independent risk factors for MGC.

Inhibition of histone methyltransferase PRMT5 attenuates cisplatin-induced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway / 药物分析学报

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Clinical analysis of different types of neonatal sepsis: a multi-center retrospective study / 中国新生儿科杂志

Objective:To study the clinical characteristics of different types of neonatal sepsis.Methods:From January 2012 to December 2019, neonates with confirmed sepsis from 5 neonatal centers of central-south China were reviewed. The neonates were assigned into early-onset sepsis (EOS) and late-onset sepsis (LOS) group, and the latter was further subgrouped into hospital-acquired LOS (hLOS) group and community-acquired LOS (cLOS) group. The etiological and clinical characteristics were analyzed. SPSS 26.0 was used for statistical analysis.Results:A total of 580 neonates were enrolled, including 286 (49.3%) in the EOS group and 294 (50.7%) in the LOS group. In LOS group, 147 were in hLOS group and 147 were in cLOS group. The gestational age and birth weight of hLOS group were significantly lower than the other two groups [(32.7±3.6) weeks vs. (37.1±3.7) weeks and (37.7±3.0) weeks, (1 810±717) g vs. (2 837±865) g and (3 024±710) g] ( P<0.05). The common pathogens in EOS and cLOS groups were coagulase-negative staphylococci and Escherichia coli, while Klebsiella pneumoniae was common in hLOS group. Carbapenems usage in the hLOS group was significantly higher than the other two groups [62.6% vs. 28.7% and 16.2%] ( P<0.05). Antibiotics duration in the hLOS group was longer than the other two groups [19 (14, 27) d vs. 15 (12, 20) d and 14 (12, 19) d] ( P<0.05). Conclusions:The clinical characteristics of neonatal sepsis vary among different types of infections, and it is necessary to establish appropriate prevention, control, diagnosis and treatment protocols.

Application and analysis of competition based training mode for first aid skills in residency program / 中华急诊医学杂志

Objective:To explore the model of first aid skills training based on competition.Method:The second-year residents who participated in the competition in 2021 ( n = 142) were selected. According to whether they attended BLS training in the first year, they were divided into group A ( n = 88) who attended BLS training and group B ( n = 54) who did not. Chi-square test, T test, Wilcoxon rank sum test and Logistic regression were used in our study. Results:There was no significant difference in gender and specialty between both groups (female, 62.5% vs. 68.5%, P= 0.466; TCM, 50% vs. 53.7%, P= 0.668), but the real resuscitation experience of group A was more than that of group B (40.9% vs. 9.3%, P= 0.000). The qualified rate of CPR and the compression score in group A was higher than that in group B [(81.8% vs. 61.1%, P = 0.006; (30±5) vs. (25 ±10), P= 0.001], including compression frequency, depth, rebound and compression/respiration rate (73.9% vs. 55.6%, P= 0.024; 88.6% vs. 70.4%, P= 0.006; 96.6% vs. 87%, P= 0.031). In the theoretical examination, the correct rates of electrocardiogram [(53.63±2.9)% vs. (50.44±2.57)%] and first aid medication [(57.38±3.55)%, P = 0.001] in the two groups were significantly lower than the qualified rate. After adjusting other factors, Logistic regression analysis showed that the CPR qualification rate in group A was 2.769 times higher than that in group B ( P= 0.015, 95% CI 1.215~6.311) Conclusions:The first aid skills training mode based on competition can objectively reflect first aid skills level of residents. We found that the quality of CPR skills was not related to gender, specialty and real CPR experiences but experience of BLS training was an independent influencing factor. And how to identify and manage arrhythmias and how to choose different emergency drugs are urgent emergency skills for residents to improve.

Expression and effect of roundabout guidance receptor 1 during valproate induced neural stem cells differentiation / 解剖学报

Objective To investigate the expression and role of roundabout guidance receptor 1 (Robo1) in the neuronal differentiation of neural stem cells (NSCs) induced by valproate (VPA). Methods The hippocampus NSCs of SD rats were isolated and cultured. Normal NSCs and VPA-treated NSCs were extracted from 10 SD rats. After VPA treatment, the proportion of neuron-specific marker β-tubulin III (Tuj1) positive neurons differentiated from NSCs were detected by immunofluorescence. The differentially expressed mRNA in normal NSCs and VPA-induced NSCs were detected by gene chip technology. After VPA treatment, the expression levels of Robo1 mRNA and protein were detected by Real-time PCR and Western blotting. The dynamic changes of Robo1 mRNA were detected by Real-time PCR after the differentiation of NSCs. After the expression of Robo1 was down-regulated in NSCs by small interfering RNA, the expression of Robo1 protein was detected by Western blotting, and the expression levels of neuron-specific markers Tuj1 and microtubule associated protein-2 (MAP-2) were detected by Real-time PCR and immunofluorescence. Results VPA induced NSCs to differentiate into neurons. Compared with the control group, the expression levels of Robo1 mRNA and protein in the differentiation of NSCs were significantly up-regulated during valproate treatment. After interference of Robo1 expression, not only Robo1 upregulation was inhibited during the differentiation of NSCs induced by VPA, but also the proportion of NSCs differentiated into neurons decreased. Conclusion VPA may promote the differentiation of NSCs into neurons by up-regulating the expression of Robo1.

Effects of traditional korean medicine Lurong Dabu Decoction on TLR4/WNT-5A signaling pathway in guinea pigs with cough variant asthma / 中国药理学通报

Aim To discuss the mechanism of Lurong Dabu Decoction on cough variant asthma. Methods Guinea pigs were divided into normal group(CON), model group(OVA), Lurong Dabu Decoction high-dose group(HIGH),low-dose group(LOW), and dexamethasone group(DEX)at random. The CVA model was established by smoking plus injection of OVA, aluminum hydroxide solution and nebulized inhalation to stimulate cough. Gguinea pigs were dissected 24 hours after the last challenge to obtain alveolar lavage fluid(BALF)and lung tissues. Immunoadsorption(ELISA)method was applied to detect the types of inflammatory cells and the content of inflammatory cytokines in BALF; HE and Masson staining of the middle lobe of the left lung were used to observe the pathological changes in lung tissues; immunohistochemical staining was used to observe TLR4 and WNT-5A protein expression and distribution of lung tissues; the protein extracted from the upper lobe of the left lung was used to measure the level of TLR4 and WNT-5A protein in lung tissues by Western blot; immunofluorescence was employed to measure the fluorescence intensity of TLR4 and WNT-5A in lung tissues; flow cytometry was used to detect IL-4 and IFN-γ in guinea pig lung tissues. Results Lurong Dabu Decoction could improve guinea pig airway inflammation, inhibit collagen fiber deposition, reduce the content of IL-4, IL-5, and IL-13 in BALF, and inhibit the protein expression of TLR4 and WNT-5A in lung tissues and increase IFN-γ levels in lung tissues while decreasing IL-4 levels. Conclusion Lurong Dabu Decoction may inhibit the occurrence of CVA through TLR4/WNT-5A signaling pathway.

Azvudine reduces the in-hospital mortality of COVID-19 patients: A retrospective cohort study

In our retrospective cohort study, we aim to explore whether Azvudine modifies the risk of death in COVID-19 patients. It was conducted on the medical records of patients, consecutively admitted for COVID-19 pneumonia to two hospitals in Chongqing, China. Based on Azvudine treatment exposure, the patients were divided into Azvudine group and non-Azvudine group. We used 1:2 ratio propensity score matching (PSM) in our study to adjust for confounding factors and differences between Azvudine and non-Azvudine groups. There were 1072 patients included in our original cohort. With 1:2 ratio PSM, the Azvudine group included 195 patients and non-Azvudine group included 390 patients. The results showed that Azvudine treatment was associated with improved in-hospital mortality in overall population (OR 0.375, 95% CI 0.225-0.623, P < 0.001), severe subgroup (OR 0.239, 95% CI 0.107-0.535, P = 0.001), critical subgroup (OR 0.091, 95% CI 0.011-0.769, P = 0.028) in matched cohort with univariate analysis. And there was a significantly lower in-hospital mortality in overall population (11% vs. 24%, P＜0.001), severe sub-group (10% vs. 32%, P < 0.001) and critical sub-group (5% vs. 34%, P = 0.017) in matched cohort. These results suggest Azvudine can reduce in-hospital mortality in overall COVID-19 patients, severe, and critical subgroup population.

Clinical Significance of co-expression of RNA Binding Protein PTBP1 and p-AXL in Osteosarcoma / 中山大学学报(医学科学版)

ObjectiveTo explore the co-expression of PTBP1 and p-AXL in osteosarcoma and its clinicopathological significance for prognosis evaluation. MethodsThe expression of PTBP1 and AXL and their prognostic value in osteosarcoma were analyzed by GEO and Target data. Paraffin biopsy specimens and clinical information from 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue （callus， osteofibrous dysplasia and osteoid ostema） were obtained from the First Affiliated Hospital of Sun Yat-sen University from March 2016 to October 2020. The expressions of PTBP1 and p-AXL proteins in osteosarcoma were detected by immunohistochemistry. ResultsGEO database showed that the expression levels of PTBP and AXL in osteosarcoma tumor group were higher than those in normal tissues， but did not reach statistical significance. Target database showed that the high expression of PTBP1 had shorter Overall survival（OS） and Progression-free survival（PFS） than low PTBP1 expression， but did not reach statistical significance （P=0.064； P=0.134）. Immunohistochemical staining included 76 cases of osteosarcoma and 37 cases of non-malignant bone tissue. The expression rate of PTBP1 and p-AXL protein in osteosarcoma tissues was higher than that in non-malignant bone tissue. The expression of p-AXL is correlated with lung metastasis （P=0.025）. Kaplan-Meier analysis showed that lung metastasis， recurrence， PTBP1 expression， co-expression of PTBP1/p-AXL influence the prognosis of patients in OS. Multivariate Cox regression analysis showed that lung metastasis （P<0.000 1） and positive expression of PTBP1 （P=0.041） were independent risk factors for osteosarcoma patients in OS. Co-expression of PTBP1 and p-AXL had shorter OS （P=0.017） and PFS （P=0.043） than non-coexpression osteosarcoma patients. ConclusionsPTBP1 and p-AXL were highly expressed in osteosarcoma tissues. The co-expression of PTBP1 and p-AXL was associated with poor prognosis of patients， and PTBP1 could be used as an independent prognostic indicator of patients with osteosarcoma.