Application value of nutritional intervention in children with acute lymphoblastic leukemia during maintenance treatment / 公共卫生与预防医学

Objective To observe the application value of nutritional intervention in children with acute lymphoblastic leukemia (ALL) during maintenance treatment. Methods A total of 75 children with ALL admitted to Hematology and Oncology Department of Children's Hospital Affiliated to Nanjing Medical University from January 2020 and January 2022 were enrolled as the research subjects. According to different intervention methods, the patients were divided into routine intervention group (n=35) and nutritional intervention group (n=40). The routine intervention group was given routine interventions and diet guidance, while the nutritional intervention group was additionally given continuous nutritional intervention. The nutritional status, anthropometry indicators [weight, upper arm circumference, triceps skin fold thickness (TSFT)], biochemical indicators (prealbumin, albumin) and incidence of complications were compared between the two groups. Results After intervention, the nutritional risk rate in the nutritional intervention group was lower than that in the routine intervention group (47.50% vs 71.43% , P<0.05), while the values of weight, upper arm circumference and TSFT were higher than those in the routine intervention group (P<0.05), the serum albumin level was higher than that in the routine intervention group (P<0.05), and the incidence of complications was lower than that in the routine intervention group (25.00% vs 48.57%, P<0.05). Conclusion Nutritional intervention is beneficial to maintain stable nutritional status, promote growth and development, and reduce the incidence of related complications in ALL children during maintenance treatment.

Moderating effect of salidroside on intestinal microbiota in mice exposed to PM2.5 / 环境与职业医学

Background Salidroside (SAL) has a protective effect on multiple organ systems. Exposure to fine particulate matter (PM2.5) in the atmosphere may lead to disruptions in gut microbiota and impact intestinal health. The regulatory effect of SAL on the gut microbiota of mice exposed to PM2.5 requires further investigation. Objective To evaluate gut microbiota disruption in mice after being exposed to PM2.5 and the potential effect of SAL. Methods Forty male C57BL/6 mice, aged 6 to 8 weeks, were randomly divided into four groups: a control group, an SAL group, a PM2.5 group, and an SAL+PM2.5 group, each containing 10 mice. In the SAL group and the SAL+PM2.5 group, the mice were administered SAL (60 mg·kg−1) by gavage, while in the control group and the PM2.5 group, sterile saline (10 mL·kg−1) was administered by gavage. In the PM2.5 group and the SAL+PM2.5 group, PM2.5 suspension (8 mg·kg−1) was intratracheally instilled, and in the control group and SAL group, sterile saline (1.5 mL·kg−1) was intratracheally administered. Each experiment cycle spanned 2 d, with a total of 10 cycles conducted over 20 d. Histopathological changes in the ileum tissue of the mice were observed after HE staining. Colon contents were collected for gut microbiota sequencing and short-chain fatty acids (SCFAs) measurements. Results The PM2.5 group showed infiltration of inflammatory cells in the ileum tissue, while the SAL+PM2.5 group exhibited only a small amount of inflammatory cell infiltration. Compared to the control group, the PM2.5 group showed decreased Shannon index (P<0.05) and increased Simpson index (P<0.05), indicating that the diversity of gut microbiota in this group was decreased; the SAL+PM2.5 group showed increased Shannon index compared to the PM2.5 group (P<0.05) and decreased Simpson index (P<0.05), indicating that the diversity of gut microbiota in mice intervened with SAL was increased. The principal coordinates analysis (PCoA) revealed a significant separation between the PM2.5 group and the control group, while the separation trend was less evident among the control group, the SAL group, and the SAL+PM2.5 group. The unweighted pair-group method with arithmetic means (UPGMA) clustering tree results showed that the control group and the SAL group clustered together first, followed by clustering with the SAL+PM2.5 group, and finally, the three groups clustered with the PM2.5 group. The PCoA and UPGMA clustering results indicated that the uniformity and similarity of the microbiota in the PM2.5 group were significantly decreased. Compared to the control group, the PM2.5 group showed decreased abundance of phylum Bacteroidetes and Candidatus_Saccharimonas (P<0.05) and increased abundance of phylum Proteobacteria, genus Escherichia, genus Bacteroides, genus Prevotella, genus Enterococcus, and genus Proteus (P<0.05). Compared to the PM2.5 group, the SAL+PM2.5 group showed decreased abundance of phylum Proteobacteria, phylum Actinobacteria, genus Prevotella, and genus Proteus (P<0.05), and increased abundance of Candidatus_Saccharimonas (P<0.05). The PM2.5 group showed reduced levels of propionic acid, valeric acid, and hexanoic acid compared to the control group (P<0.05), while the SAL+PM2.5 group showed increased levels of propionic acid, isobutyric acid, butyric acid, valeric acid, and hexanoic acid compared to the PM2.5 group (P<0.05). Conclusion Exposure to PM2.5 can cause pathological alterations, microbial dysbiosis, and disturbing production of SCFAs in intestinal tissue in mice. However, SAL can provide a certain degree of protective effect against these changes.

Bioequivalence of metformin hydrochloride sustained-release tablets under fed condition in healthy subjects / 中国药科大学学报

@#To evaluate bioequivalence and safety of two kinds of metformin hydrochloride sustained-release tablets (test preparation vs reference preparation) under the condition of fed and single administration.A single center, randomized, open, single-dose, two-period, two-sequence, and double-crossover design was used.32 healthy subjects took 0.5 g of test preparation or reference preparation under fed and single-dose administration.4 mL of venous blood was collected from before administration (0 h) to 1, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 15, 24, 36 and 48 h after administration.The concentration of metformin in plasma samples was detected, and then the pharmacokinetic parameters were calculated by WinNonlin 7.0 software.When the 90% confidence intervals of cmax, AUC0-t and AUC0-∞ geometric mean ratio of test preparation and reference preparation were within 80.00%-125.00% equivalent intervals respectively, the bioequivalence of the two preparations was proved.One subject fell off due to adverse events.The main pharmacokinetic parameters of test preparation and reference preparation as follows: cmax were (0.68 ± 0.14) and (0.65 ± 0.11) mg/L, AUC0-t were (7.33 ± 1.65) and (7.00 ± 1.89) h·mg/L, AUC0-∞ were (7.39 ± 1.67) and (7.06 ± 1.91) h·mg/L, respectively.The 90% confidence intervals of the geometric mean ratio of the two main pharmacokinetic parameters were 101.45%-109.14%, 100.08%-112.32% and 100.24%-112.28%, respectively, which fell within the bioequivalence interval of 80.00%-125.00%.There were no serious adverse events and unexpected adverse events during the trial.The results show that test preparation and reference preparation are bioequivalent under fed and single-dose administration, safe and well tolerated in healthy subjects.

Monoterpenes and hexenol glycosides from an aqueous extract of Monochasma savatieri / 药学学报

Twelve compounds, including 5 new monoterpenes and 7 known derivatives, were isolated from a water decoction of Monochasma savatieri by column chromatography over macroporous adsorbent resin, MCI resin, Sephadex LH-20, and HW-40C, combined with preparative TLC, reversed phase HPLC, and flash column chromatographic techniques. Their structures were elucidated by comprehensive analysis of spectroscopic data, along with enzymatic hydrolysis as well as electronic circular dichroism (ECD) and NMR calculations, the new structures named monochaside I (1) and monochairidols A-D (2-5), respectively. The known compounds 6-12 were obtained from the Monochasma plants for the first time.

Analysis of genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine / 浙江大学学报·医学版

OBJECTIVES@#To investigate the genotypes and biochemical phenotypes of neonates with abnormal metabolism of butyrylcarnitine (C4).@*METHODS@#One hundred and twenty neonates with increased C4 levels detected by tandem mass spectrometry in the neonatal screening at Children's Hospital, Zhejiang University School of Medicine from January 2018 to June 2023 were included. The initial screening data and recalled data of C4 and C4/C3 were collected and converted into multiples of C4 reference range. Next generation sequencing was performed and the exons with adjacent 50 bp regions of ACAD8 and ACADS genes were captured by liquid phase capture technique. Variant information was obtained by bioinformatic analysis and the pathogenicity were classified according to the American College of Medical Genetics and Genomics criteria. The Wilcoxon rank sum test was used to analyze the differences in C4 levels among neonates with different variation types.@*RESULTS@#In total, 32 variants in ACAD8 gene were detected, of which 7 variants were reported for the first time; while 41 variants of ACADS gene were detected, of which 17 variants have not been previously reported. There were 39 cases with ACAD8 biallelic variations and 3 cases with ACAD8 monoallelic variations; 34 cases with ACADS biallelic variations and 36 cases with ACADS monoallelic variations. Furthermore, 5 cases were detected with both ACAD8 and ACADS gene variations. Inter group comparison showed that the multiples of C4 reference range in initial screening and re-examination of the ACAD8 biallelic variations and ACADS biallelic variations groups were significantly higher than those of the ACADS monoallelic variations group (all P<0.01), while the multiples in the ACAD8 biallelic variations group were significantly higher than those in the ACADS biallelic variations group (all P<0.01). The multiples of C4 reference range in the initial screening greater than 1.5 times were observed in all neonates carrying ACAD8 or ACADS biallelic variations, while only 25% (9/36) in neonates carrying ACADS monoallelic variations.@*CONCLUSIONS@#ACAD8 and/or ACADS gene variants are the main genetic causes for elevated C4 in newborns in Zhejiang region with high genotypic heterogeneity. The C4 levels of neonates with biallelic variations are significantly higher than those of neonates with monoallelic variations. The cut-off value for C4 level could be modestly elevated, which could reduce the false positive rate in tandem mass spectrometry neonatal screening.

Clinical significance and risk factors of redundant nerve root in patients with lumbar spinal stenosis / 中国骨伤

OBJECTIVE@#To investigate the clinical significance and screen the risk factors of redundant nerve roots(RNRs) in patients with lumbar spinal stenosis.@*METHODS@#The clinical data of 196 patients with lumbar spinal stenosis in the department of Spinal Surgery, Yijishan Hospital, Wannan Medical College from April 1, 2015 to November 30, 2020 were retrospectively analyzed. All patients were divided into RNRs positive group and RNRs negative group according to the presence of RNRs. The differences in general clinical data, imaging parameters, visual analogue scale(VAS), Oswestry disability index(ODI), and other indicators between the two groups were compared. The risk factors which are highly correlated with RNRs were screened by binary Logistic regression analysis.@*RESULTS@#There were 59 cases in the RNRs positive group, with an occurrence rate of 29.95% (59/137), and 137 cases in the RNRs negative group. The incidence rate of RNRs in 196 patients with lumbar spinal stenosis was 30.10% (59/196). VAS and ODI scores of patients in the two groups were statistically significant (P<0.05), and clinical symptoms of patients in the RNRs positive group were more severe than those in the RNRs negative group. There were significant differences in age, number of stenosis segments, average area of lumbar dural sac, area of the narrowest segment and the narrowest segment(P<0.05). Binary logistic regression analysis showed that the number of stenosis segments, the average median sagittal diameter of spinal canal, and the average area of dural sac in lumbar intervertebral space were correlated with the generation of RNRs (P<0.05). The regression coefficient of the number of stenosis segments was -1.115, the regression coefficient of the median sagittal diameter of the spinal canal was -1.707, and the regression coefficient of the mean dural sac area of the lumbar intervertebral space was 7.556.@*CONCLUSION@#The clinical symptoms of patients with lumbar spinal stenosis accompanied by RNRs are more severe than those without them. The number of narrow segments, median sagittal diameter of the spinal canal, and the area of the lumbar intervertebral dural sac are the high-risk factors for RNRs, with the area of the lumbar intervertebral dural sac has the highest correlation.

Analysis of recurrent factors and therapeutic effect after laparoscopic inguinal hernia repair / 中华外科杂志

Objective: To analyze the recurrence factors and reoperation effect of laparoscopic inguinal hernia repair. Methods: A total of 41 patients with recurrence after laparoscopic repair of the inguinal hernia admitted to the Department of Hernia and Abdominal Wall Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2017 to December 2021 were retrospectively analyzed. All patients were males, aging (62±7) years (range: 51 to 75 years). The recurrence intervals were 3 days to 7 years postoperatively. The surgical methods, causes of recurrence, and treatment outcomes of the patients were analyzed. Fisher exact probability method is used to compare the rates. Results: Among all cases, the primary surgical procedures included transabdominal preperitoneal herniorrhaphy (TAPP) in 31 cases and total extraperitoneal herniorrhaphy in 10 cases. The reoperative procedures included the TAPP of 11 cases and the Lichtenstein procedure of 30 cases. The factors of recurrent cases in all patients could be divided into 4 categories, including insufficient mesh coverage in 23 cases, mesh curling in 9 cases, mesh contractuture in 7 cases, and improper mesh fixation in 2 cases. Recurrence, infection, chronic pain, foreign body sensation didn't occur in the followed period of(M(IQR)) 18(24) months(range: 12 to 50 months). There was no statistical difference in the incidence of postoperative seroma between the TAPP and Lichtenstein procedure (3/11 vs. 20.0% (6/30), P=0.68). Conclusions: Postoperative recurrence of laparoscopic inguinal hernia is mostly caused by the lack of mesh coverage. Due to the emphasis on standardized surgical operation, a good outcome could be achieved through reoperation by the TAPP or Lichtenstein procedure.

Clinical value of the MeltPro MTB assays in detection of drug-resistant tuberculosis in paraffin-embedded tissues / 中华病理学杂志

Objective: To evaluate the clinical value of the MeltPro MTB assays in the diagnosis of drug-resistant tuberculosis. Methods: A cross-sectional study design was used to retrospectively collect all 4 551 patients with confirmed tuberculosis between January 2018 and December 2019 at Beijing Chest Hospital, Capital Medical University. Phenotypic drug sensitivity test and GeneXpert MTB/RIF (hereafter referred to as "Xpert") assay were used as gold standards to analyze the accuracy of the probe melting curve method. The clinical value of this technique was also evaluated as a complementary method to conventional assays of drug resistance to increase the detective rate of drug-resistant tuberculosis. Results: By taking the phenotypic drug susceptibility test as the gold standard, the sensitivity of the MeltPro MTB assays to detect resistance to rifampicin, isoniazid, ethambutol and fluoroquinolone was 14/15, 95.7%(22/23), 2/4 and 8/9,respectively; and the specificity was 92.0%(115/125), 93.2%(109/117), 90.4%(123/136) and 93.9%(123/131),respectively; the overall concordance rate was 92.1%(95%CI:89.6%-94.1%),and the Kappa value of the consistency test was 0.63(95%CI:0.55-0.72).By taking the Xpert test results as the reference, the sensitivity of this technology to the detection of rifampicin resistance was 93.6%(44/47), the specificity was100%(310/310), the concordance rate was 99.2%(95%CI:97.6%-99.7%), and the Kappa value of the consistency test was 0.96(95%CI:0.93-0.99). The MeltPro MTB assays had been used in 4 551 confirmed patients; the proportion of patients who obtained effective drug resistance results increased from 83.3% to 87.8%(P<0.01); and detection rate of rifampicin, isoniazid, ethambutol, fluoroquinolone resistance, multidrug and pre-extensive drug resistance cases were increased by 3.2%, 14.7%, 22.2%, 13.7%, 11.2% and 12.5%, respectively. Conclusion: The MeltPro MTB assays show satisfactory accuracy in the diagnosis of drug-resistant tuberculosis. This molecular pathological test is an effective complementary method in improving test positivity of drug-resistant tuberculosis.

Research advances in the role of / 临床肝胆病杂志

Alcoholic liver disease (ALD) is one of the most common chronic liver diseases worldwide and includes the different stages of steatosis, steatohepatitis, fibrosis, and liver cirrhosis. Enterococcus faecalis is a common bacterium for nosocomial infection and has a significant impact on the prognosis of patients with alcoholic hepatitis. This review mainly introduces the pathogenesis of ALD and the pathogenic mechanism of E. faecalis , summarizes the research advances in E. faecalis in ALD, and briefly describes the detection and treatment methods for E. faecalis infection in clinical practice. Since there is an extremely high mortality rate in ALD patients with lytic E. faecalis infection, an in-depth understanding of E. faecalis has become an important issue nowadays.

Nonalcoholic fatty liver disease and bilirubin: correlation, mechanism, and therapeutic perspectives / 中华肝脏病杂志

Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related disorder induced by multiple factors and mainly characterized by excessive fat buildup in hepatocytes. With the consumption of a Western-style diet and obesity prevalence in recent years, the incidence of NAFLD has gradually increased, becoming an increasingly serious public health problem. Bilirubin is a heme metabolite and a potent antioxidant. Studies have demonstrated that bilirubin levels have an inverse correlation with the incidence rate of NAFLD; however, which form of bilirubin plays the main protective role is still controversial. It is considered that the main protective mechanisms for NAFLD are bilirubin antioxidant properties, insulin resistance reduction, and mitochondrial function. This article summarizes the correlation, protective mechanism, and possible clinical application of NAFLD and bilirubin.

Associations of all-cause mortality with admission blood pressure variability during multiple hospitalizations in acute decompensated heart failure / 中华心血管病杂志

Objective: To investigate whether admission blood pressure (BP) variability during multiple hospitalizations is associated with all-cause mortality independent of baseline BP in acute decompensated heart failure (ADHF). Methods: Patients with ADHF admitted to the Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University from September 2013 to December 2017 were retrospectively enrolled. The risk of all-cause mortality associated with indices of BP variability, including mean admission BPs, standard deviation of BP and coefficient of variation of BP during multiple hospitalizations was assessed, using Cox regression model. Results: A total of 1 006 ADHF patients (mean aged (69.3±13.5) years; 411 (40.8%) female; 670 (66.6%) with preserved ejection fraction) were enrolled. During a median follow-up of 1.54 years, 47.0% of patients died. In all ADHF patients, after adjusting for confounding factors, for every 1-standard deviation (SD) increase in SD and coefficient of variation (CV) of systolic BP, the risk of all-cause mortality increased by 10% and 11%, respectively (SD: HR, 1.10, 95%CI, 1.01-1.21, P=0.029, CV: HR, 1.11, 95%CI, 1.02-1.21, P=0.017); for every 1-SD increase in the mean of diastolic BP, the risk of all cause mortality decreased by 25% (HR, 0.75; 95%CI, 0.65-0.87; P<0.001). In ADHF patients with preserved ejection fraction, after accounted for potential confounders, higher SD and CV of admitted systolic and diastolic BP were significantly associated with higher risk of all-cause mortality, regardless of whether confounding factors were adjusted (P≤0.049); After adjusting for confounding factors, the risk of all-cause mortality increased by 18% and 19% for every 1-SD increase in SD and CV of systolic BP, while the risk of all-cause mortality increased by 11% and 15% for every 1-SD increase in SD and CV of diastolic BP. In ADHF patients with reduced ejection fraction, after adjusting for confounding factors, the higher the mean admission systolic BP during multiple hospitalizations, the lower the risk of total mortality (HR, 0.68; 95%CI, 0.47-1.00; P=0.049). Conclusions: In patients with ADHF, independent of baseline BP, BP variability during multiple hospitalizations was strong predictor of all-cause mortality.

Application of standardized patient teaching based on Calgary-Cambridge communication model in nurse patient communication training for junior college interns / 中国实用护理杂志

Objective:To explore the effect of applying standardized patient teaching based on Calgary-Cambridge communication model in nurse patient communication training for junior college interns, and to enrich the teaching methods of nurse patient communication training in domestic medical institutions.Methods:This study was a quasi-experimental study. In July 2022, 78 students were selected from 335 junior college interns in the First Affiliated Hospital of Shandong First Medical University by random coding method, and were randomly divided into the experimental group (39 students) and the control group (39 students) by lot. The control group received routine training. The experimental group received standardized patient teaching based on Calgary Cambridge communication model: teaching the key points of communication, guiding demonstration based on Calgary Cambridge communication model, and guiding reflection and exploration. The nurse patient communication ability, nurse patient communication practice skills, communication self-efficacy, and teaching satisfaction of the two groups of interns were compared between the two groups after 8 weeks of training.Results:After training, the total score of nurse patient communication ability evaluation in the experimental group was (91.41 ± 5.35) points, higher than that in the control group (88.08 ± 7.40) points, there was significant difference ( t=2.24, P<0.05); after training, the communication self-efficacy score of the experimental group was (30.21 ± 4.28) points, higher than that of the control group (27.94 ± 5.09) points, there was significant difference ( t=2.09, P<0.05); the total score of communication practice skills in the experimental group was (173.59 ± 18.48) points, higher than that in the control group (158.44 ± 15.57) points, there was significant difference ( t=3.82, P<0.05); the total score of communication teaching and training satisfaction in the experimental group was (16.77 ± 2.94) points, higher than that in the control group (15.22 ± 1.90) points, and there was significant difference ( t=2.68, P<0.05). Conclusions:The standardized patient teaching based on Calgary Cambridge communication model can effectively improve the practical skills of nurse patient communication of junior college interns, and promote the improvement of their nurse patient communication self-efficacy, which is conducive to the improvement of nurse patient communication ability junior college intern.

Genetic analysis of neonates with abnormal isovaleryl carnitine metabolism / 中华实用儿科临床杂志

Objective:To explore the genetic causes of abnormal isovaleryl carnitine (C5) metabolism in newborns.Methods:Retrospective study.The screening and clinical follow-up data of 34 neonates with elevated C5 levels shown by the tandem mass spectrometry test in Children′s Hospital, Zhejiang University School of Medicine from January 2018 to December 2021 were collected.Afterwards, their ethylenediaminetetraacetic acid (EDTA) anticoagulant venous blood was collected to extract genomic DNA.A total of 79 genes related to genetic metabolic diseases, such as ACADSB, IVD and ACADM, were captured by liquid-phase capture technology.High-throughput sequencing and bioinformatics analysis were used to acquire gene variation information and the genes were categorized by American College of Medical Genetics and Genomics classification standard.According to the results of genetic analysis, the newborns with C5 elevation were divided into 3 groups: non-mutation group(11 cases), ACADSB mutation group(16 cases) and IVD mutation group(7 cases). Wilcoxon rank sum test was performed to analyze the difference between these groups. Results:Among 34 neonates, 6 ACADSB variants were detected in 16 cases, and 2 of them [c.461G>A (p.G154E), c.746delC(p.P249Lfs*15)] were novel variants.Eleven IVD variants were detected in 7 cases, and 7 of them [c.118A>G(p.N40D), c.296-10C>G, c.302A>G(p.Y101C), c.537G>A(p.M179I), c.667C>T(p.R223W), c.983A>G(p.K328R), c.1147+ 5G>A] were never reported before.There was no significant difference in the C5 concentration in initial screening among the three groups ( P>0.05). Conclusions:Mutations in ACADSB and IVD genes are the main causes of augmented C5 levels in neonatal screening.For newly discovered genetic variants, functional prediction by multiple bioinformatics analysis software is recommended.And it is also important to carry out clinical follow-up and evaluation.

Detection performance of Al 18F-PSMA-BCH PET/CT in early relapsed prostate cancer after radical prostatectomy / 中华核医学与分子影像杂志

Objective:To assess the performance of Al 18F-prostate specific membrane antigen (PSMA)-BCH PET/CT in the detection and localization of early recurrent prostate cancer after radical prostatectomy. Methods:From July 2021 to July 2022, a cohort of 51 patients (age: 49-80(64.8±6.9) years) who underwent Al 18F-PSMA-BCH for biochemical recurrence with the prostate specific antigen (PSA) level less than 2 μg/L in Peking University Cancer Hospital & Institute were retrospectively analyzed. The patients were stratified into 4 groups (PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L, 1 μg/L≤PSA<2 μg/L groups) according to different PSA levels. Lesions detected by Al 18F-PSMA-BCH PET/CT were recorded as prostate bed (including bed of seminal vesicles); pelvic, paraaortic, mediastinal/supraclavicular and axillary lymph nodes; bone lesions and visceral lesions. The detection rates among different groups were compared by Fisher exact test. Results:Of 51 patients, 30(58.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer, with 60.0%(18/30) had disease confined to the pelvis, including 26.7%(8/30) had prostate bed recurrence, 26.7%(8/30) had pelvic lymph nodes, 6.6%(2/30) had prostate bed recurrence with pelvic lymph nodes, while 40.0%(12/30) had extra pelvic disease. The detection rates of Al 18F-PSMA-BCH PET/CT in PSA<0.2 μg/L, 0.2 μg/L≤PSA<0.5 μg/L, 0.5 μg/L≤PSA<1 μg/L and 1 μg/L≤PSA<2 μg/L groups were 39.1%(9/23), 6/11, 8/9 and 7/8, respectively. There were no significant differences of detection rates between PSA<0.2 μg/L group and 0.2 μg/L≤PSA<0.5 μg/L group ( P=0.397) and also between 0.5 μg/L≤PSA<1 μg/L group and 1 μg/L≤PSA<2 μg/L group ( P=0.929). Conclusion:Al 18F-PSMA-BCH has a high detection rate for early recurrent prostate cancer, even at low PSA levels less than 0.2 μg/L.

Resting-state brain function MRI study of spinocerebellar ataxia type 3 based on amplitude of low-frequency fluctuation / 中华放射学杂志

Objective:To explore functional brain region changes and their correlation with behavioral variables based on amplitude of low-frequency fluctuation (ALFF) analysis using resting-state functional MRI (rs-fMRI) in patients with spinocerebellar ataxia type 3 (SCA3).Methods:In this prospective study, patients with SCA3 and healthy controls (HC) were recruited by Southwest Hospital, Army Medical University from May 2017 to March 2022. All subjects completed the scale for assessment and rating of ataxia (SARA), the international cooperative ataxia rating scale-posture and gait (ICARS-p&g), the rapid verbal retrieval (RVR) and Montreal cognitive assessment (MoCA). Meanwhile, the subjects underwent structural MRI and rs-fMRI scans. The MRI data were processed by DPABI software based on MATLAB. The normalized ALFF values of the two groups were compared using two-sample t-test, and the changes of ALFF values in the brain regions of SCA3 and HC groups were analyzed with the t-test of partial correlation coefficient. Spearman correlation analysis was used to evaluate the relationship between the ALFF values of abnormal brain area and the score of neurobehavioral scale in SCA3. Results:Compared with HC group, ALFF significantly increased in the left cerebellum (Crus1, Crus2, 4_5, 6, 7b, 8, 9), right cerebelum_9, left fusiform gyrus and vermis_8; while ALFF significantly decreased in the vermis_4_5 in patients with SCA3. Correlation analysis showed that ALFF values in the left cerebellar_8 were negatively correlated with RVR scores ( r=-0.293, P=0.035), ALFF values in the left cerebellar_9 were negatively correlated with MoCA scores ( r=-0.324, P=0.019), ALFF values in the right cerebellar_9 were negatively correlated with RVR scores ( r=-0.401, P=0.003) in the SCA3 patients. ALFF in the vermis_8 was positively correlated with SARA scores ( r=0.308, P=0.026) and ICARS-p&g scores ( r=0.313, P=0.024) in the SCA3 patients. Conclusion:There are significant changes in ALFF values in the cerebellum and left fusiform gyrus in patients with SCA3, and the changes of ALFF values are closely related with communication, cognitive and movement disorders.

Deubiquitinase JOSD2 Promotes the Survival and Metastasis of Hepatoma Cells / 中国生物化学与分子生物学报

Ubiquitination is a reversible post-translational modification that regulates protein stability and plays a function in numerous signaling pathways. Deubiquitinases play important roles in the regulation of the occurrence and development of different cancers. In this study, we analyzed the survival and prognosis of liver cancer patients according to the expression levels of 63 deubiquitinases. Results discovered that JOSD2 expression in tumor was significantly higher than that in the adjacent tissue (P<0. 0001) and was negatively associated with overall survival of patients (P < 0. 05). JOSD2 is a deubiquitinase from MJD sub-family. Other members of this sub-family were not correlated with liver cancer. The pathways related to cell proliferation were significantly enriched (FDR < 0. 05) in a differential gene function enrichment analysis of JOSD2 high-expressing samples in TCGA data. In hepatoma cell lines, we demonstrated that the overexpression of JOSD2 significantly enhances cell survival, migration and invasion. In conclusion, this study found that JOSD2 is highly expressed in liver cancer (P = 0. 041), and that patients with high-expressed JOSD2 have significantly shorter overall survival. Furthermore, overexpression of JOSD2 can promote the survival and metastasis of hepatoma cells (P < 0. 01), which suggests that JOSD2 might promote the survival and metastasis of hepatocellular carcinoma.

Inhibitory effect of LZJ541, a novel small molecule inhibitor of STAT3, on the proliferation of hepatocellular carcinoma cells / 药学学报

Signal transducer and activator of transcription 3 (STAT3) is an important regulatory factor of cell proliferation and metastasis, involved in the occurrence and development of a variety of malignant tumors, and it is one of the hot spots in the research of targeted anti-tumor drugs. Our group screened a novel benzobis (imidazole) structure small molecule compound LZJ541 through the screening model of Janus kinase (JAK)/STAT3 pathway inhibitors, which has definite STAT3 inhibitory activity. We examined the effect of LZJ541 on the proliferation of HepG2 and PC-3 cells by MTT assay in vitro, detected the effect of LZJ541 on the expression of STAT3-related proteins in HepG2 cells by Western blot, and measured the effect of LZJ541 on the apoptosis and cell cycle arrest of HepG2 cells via flow cytometry. The results indicated that LZJ541 significantly inhibited the activation of STAT3 signaling pathway and restrained the proliferation of HepG2 cells. Its half maximal inhibitory concentration (IC50) was 13.8 μmol·L-1, which was much lower than that of PC-3 cells (with low STAT3 expression, IC50: 41.99 μmol·L-1), LZJ541 can also inhibit the phosphorylation of STAT3 in HepG2 cells, thereby inducing apoptosis and cycle arrest and then exerting anti-tumor effects. In conclusion, LZJ541 has a certain anti-tumor effect in vitro, which provides an experimental basis for the development of new STAT3-targeted anti-tumor drugs around this kind of compounds.

Application of 3D printed model assisted network teaching in clinical probation of neurosurgery / 中华医学教育探索杂志

Objective:To explore the effect of the 3D printed model assisted network teaching of neurosurgery.Methods:Seventy-six probation students were divided into: 3D printed model assisted online course teaching group (test group) and traditional teaching group (control group). After 1-month online teaching, quantitative assessment and satisfaction survey were carried out. SPSS 17.0 was used for statistical analysis of variance.Results:The department graduation test (theory and operation) scores of students in the test group were (86.7±7.4) points, which was significantly higher than those in the control group (78.2±8.2) points ( t=5.56, P<0.01). The teaching satisfaction survey showed that the test group had significantly higher scores in self-evaluation of spatial imagination ( t=3.81, P<0.01), deepening understanding of neuroanatomy ( t=5.29, P<0.01), and increasing interest in clinical learning ( t=5.12, P<0.01) than those of the control group. Conclusion:Compared with the conventional online teaching methods, 3D printed model assisted online teaching helps to improve teaching quality and students' satisfaction.

Validation of compound C19 as a glutaminase C inhibitor / 药学学报

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

The predictive value of 18F-PSMA PET/CT-derived prostate specific membrane antigen expression parameters for the risk of metastasis in elderly prostate cancer patients / 中华老年医学杂志

Objective:To investigate the value of 18F-PSMA PET/CT-derived prostate specific membrane antigen(PSMA)expression parameters, including maximum standardize uptake value(SUV max), PSMA receptor expressing tumor volume(PSMA-TV), and total lesion PSMA receptor expression(TL-PSMA), in predicting the risk of metastasis in elderly prostate cancer patients aged 60 years and older. Methods:Clinical data of 39 patients with prostate cancer diagnosed in our hospital from January 2019 to May 2021 and imaging data of 18F-PSMA PET/CT before treatment were analyzed retrospectively.PSMA-TV and TL-PSMA of primary tumor tissue were calculated from PET/CT images with 40% of the SUV max as the threshold value.The influence of 18F-PSMA PET/CT on clinical TNM staging was evaluated.The Mann-Whitney U test was used to compare the differences in values of various indicators between the groups with or without metastasis, including the total prostate-specific antigen(tPSA)level, Gleason score and PSMA expression parameters.The correlation of PSMA expression parameters with tPSA and Gleason score was analyzed.The area under the receiver operating characteristic(ROC)curve(AUC)was used to determine the predictive ability of different indicators for the risk of prostate cancer metastasis, and multivariate logistic regression analysis was used to screen for independent predictors of prostate cancer metastasis. Results:The Gleason score of 39 prostate cancer patients(median age: 67 years, age range: 60-83 years)was 7.0(7.0, 8.0), and the median prostate specific antigen(PSA)level was 14.83(7.37, 30.93)μg/L.There were 11 cases(28.2%)with metastasis(the metastasis group), and 28 cases(71.8%)without metastasis(the non-metastasis group). Based on PET/CT, the clinical N and M stages of five patients(12.8%)were changed, but two cases(5.1%)with pelvic lymph node metastasis were missed.The median ages of the metastasis group and the non-metastasis group were 63(60-79)years and 69(60-83)years, respectively, and the difference was not statistically significant( P=0.115). The metastasis group and the non-metastasis group had tPSA levels at 54.0(9.9, 75.8)μg/L and 10.2(6.8, 22.8)μg/L, the SUV max at 29.1(16.8, 35.3)and 7.7(6.0, 13.6), the PSMA-TV at 41.5(22.4, 90.9)cm 3 and 6.8(3.6, 9.3)cm 3, TL-PSMA at 279(139.7, 996.4)and 25.5(15.9, 37.0), Gleason scores at 8.0(7.0, 8.0)and 7.0(7.0, 8.0), respectively.There were statistically significant differences in tPSA( Z=-2.528, P=0.011), SUV max( Z=-4.151, P<0.001), PSMA-TV( Z=-3.995, P<0.001)and TL-PSMA( Z=-4.213, P<0.001)between the two groups.SUV max( r=0.537, P<0.01), PSMA-TV( r=0.496, P<0.01)and TL-PSMA( r=0.508, P<0.01)were all positively correlated with tPSA.Furthermore, SUV max( r=0.547, P<0.01), PSMA-TV( r=0.412, P<0.01)and TL-PSMA( r=0.433, P<0.01)were also positively correlated with Gleason score.ROC curve analysis showed that the AUCs of SUV max, PSMA-TV, TL-PSMA and tPSA in predicting prostate cancer metastasis were 0.932, 0.916, 0.938 and 0.763, respectively.Multivariate Logistic regression analysis showed that SUV max( OR=1.203, 95% CI: 1.001-1.445, P=0.049)was an independent predictor of prostate cancer metastasis. Conclusions:These PSMA expression parameters of 18F-PSMA PET/CT have a good value in predicting the risk of metastasis in elderly prostate cancer patients, and SUV maxmay serve as a potential molecular imaging indicator to independently predict prostate cancer metastasis.