Objective:To explore the prevalence, clinical features, genetic characteristics and prognosis of Citrin deficiency in Henan province of China.Methods:A total of 986 565 neonates screened by tandem mass spectrometry at the Third Affiliated Hospital of Zhengzhou University from January 2013 to December 2021 were retrospectively analyzed. Analysis of SLC25A13 gene variants and parental verification were carried out for neonates suspected for Citrin deficiency by next-generation sequencing. The clinical, biochemical and genetic characteristics of Citrin deficiency patients were integrated to guide the diet treatment and follow up the growth and development. Paired- t test was used to compare the amino acid levels in the peripheral blood samples before and after the treatment. Results:Nine cases of Citrin deficiency were diagnosed among the 986 565 neonates. Specific elevation of citrulline was observed in all of the 9 cases. Six variants were detected by genetic sequencing, among which c. 852_855delTATG, c. 615+ 5G>A, c. 550C>T and IVS16ins3kb were known pathogenic variants, whilst c. 1111_1112delAT and c. 837T>A were unreported previously. The detection rate for c. 852_855delTATG was the highest (61.6%, 11/18), followed by IVS16ins3kb (16.7%, 3/18). The clinical symptoms of all patients were relieved after the treatment, and the blood amino acid profile and biochemical parameters were significantly improved by gradually falling within the normal range. By June 2022, all patients had shown a good prognosis.Conclusion:The prevalence of Citrin deficiency among neonates from Henan Province by tandem mass spectrometry is 1/109 618, and the carrier rate for the pathogenic variants of the SLC25A13 gene was 1/166. The c. 852_855delTATG may be a hot spot variant among the patients. Discovery of the novel variants has enriched the mutational spectrum of the SLC25A13 gene. Above results have provided a basis for the early diagnosis, treatment, prognosis and genetic counseling for the affected families.

Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Objective:To explore the effect of a new teaching mode, which includes bridge-in, outcome, pre-test, participation, post-test and summary (BOPPPS), on the online teaching of radiobiology related knowledge for cancer radiotherapy practitioners.Methods:Taking the cell survival curve, cell cycle and radiosensitivity as examples, the radiotherapy practitioners in multiple university-affiliated hospitals were organized to carry out a multicenter prospective randomized control study. All practitioners were randomly divided into BOPPPS group and control group. The courses for BOPPPS group were designed as an online classroom, consisting of pre-class preparation, online teaching and post-class stages. The online teaching stage included video viewing, basic knowledge learning, literature discussion, group discussion and others. The control group employed the traditional teaching mode. The χ2 test was used to compare the consistency of general conditions between the two groups, and nonparametric test was used to compare the differences in scores between two or more groups. Results:The score of the pre-class test was 58.56 ± 0.99. Post-class average score for BOPPPS group was 85.48±0.85 and for control group 77.79±1.10, with the former being higher 7.69 ( Z=5.31, P<0.001) than the latter. The average answer time was (296.62±15.40) s for BOPPPS group and (386.41±21.27) s for control group, with the former being shorter 89.79 s ( Z=3.34, P=0.001) than latter. Subgroup analysis shown that the scores of BOPPPS group were significantly rising, regardless of whether or not the students had studied radiobiology courses. Among the students who have not studied these courses, the scores were rising greatly. Moreover, From the analysis of different positions, it was found that both the scores of BOPPPS group and control group have risen, especially for doctors, deputy chief doctors, physicists and technicians. There were also statistically differences between different degrees, with significantly rise in scores for undergraduate and doctoral students ( Z=3.64, 4.18, P<0.001). Conclusions:The flexible application of BOPPPS teaching mode to the online education of such boring disciplines, like radiobiology, is of great significance to raise the theoretical basis of radiotherapy practitioners.

Objective: To analyze the spatio-temporal distribution characteristics of new HIV/AIDS cases at ages of 50 years and older in Wenzhou City from 2006 to 2020, so as to provide insights into precise control of AIDS. Methods : The data of new HIV/AIDS cases aged 50 years and older in Wenzhou City from 2006 to 2020 were collected from the China Information System for Disease Control and Prevention. The temporal and spatial distribution characteristics of new HIV/AIDS cases at ages of 50 years and older were identified using global and local spatial autocorrelation analyses and spatial-temporal scan analysis. Results: Totally 1 917 new HIV/AIDS cases aged 50 years and older were detected in Wenzhou City from 2006 to 2020, and there were 179 new HIV/AIDS cases in 58 townships ( streets ) from 2006 to 2010, 643 cases in 113 townships ( streets ) from 2011 to 2015 and 1 095 cases in 147 townships ( streets ) from 2016 to 2020, respectively. The distribution of new HIV/AIDS cases appeared positive spatial autocorrelations from 2006 to 2010 ( Moran's I value=0.05, Z=1.976, P=0.046 ), from 2011 to 2015 ( Moran's I value=0.08, Z=2.314, P=0.028) and from 2016 to 2020 (Moran's I value=0.18, Z=3.956, P=0.003 ). Spatial-temporal scan analysis identified two clusters. The primary cluster mainly covered 70 towns ( streets ) in Lucheng Distrct, Ouhai District, Longwan District, Economic and Technical Development Region, Rui' an City and Pingyang County of Wenzhou City from January 1, 2014 to December 31, 2020, with a cluster radius of 34.30 km [log likelihood ratio ( LLR )=192.84, RR=2.60, P<0.001], and the secondary cluster was located in Hongqiao Township of Yueqing City from January 1, 2009 to December 31, 2015, with a cluster radius of 0 ( LLR=90.60, RR=7.27, P<0.001 ). Conclusions The number of new HIV/AIDS cases aged 50 years and older appeared a tendency towards a rise in Wenzhou City from 2006 to 2020, with spatial clusters that were predominantly identified in urban areas, Rui' an City and Pingyang County of Wenzhou City.

Objective To evaluate the efficacy of the new treatment regimen versus the standardized scheme for the initial treatment of smear-positive tuberculosis in the elderly.Methods A total of 302 elderly patients meeting the inclusion and exclusion criteria were selected from 14 tuberculosis-designated medical institutions in Beijing.The patients received the initial treatment of smear-positive tuberculosis from January 2014 to August 2016 in the combined prospective and retrospective study.All patients were divided into observation group(n=63)receiving treatment with 6L2 HELfx regimen from August 1,2015 to August 31,2016,and control group (n =239) receiving treatment with 6L2HELfx regimen from January 1,2014 to January 31,2015.The nation-unified standard chemotherapy regimen 2RHZE/4RH was used in tuberculosis medical service institutions for all patients.The differences between the two groups were analyzed and compared in the completion of treatment,negative conversion of sputum culture or smear,adverse drug reactions and treatment outcome.Results The completion rate of long-course therapy was significantly higher in the observation group than in control group [90.5％ (57/63) vs.79.5％ (190/239),x2 =4.034,P =0.045].The rate of negative conversion of sputum culture or smear at the end of the 2nd month was higher in the observation group than in control group,but had no significant difference[87.0％ (47/54)vs.81.6％(155/190),x2 =0.879,P=0.349].The incidence of adverse reactions was much lower in observation group than in control group[46.0％ (29/63) vs.65.3％ (156/239),x2 =7.777,P =0.005].The success rate of treatment(cure or completion of long-course therapy)was higher in observation group than in control group [90.5％ (57/63) vs.77.4％ (185/239),x2 =5.350,P =0.021].ConclusioNS As compared with the standard chemotherapy regimen,the L and Lfxcontaining treatment regimen has better effects,higher success rate of treatment and less adverse reactions in elderly patients with the initial treatment of smear-positive tuberculosis.

Objective To investigate the effect of replacing a smaller-size catheter after tubularized incised plate (TIP) urethroplasty on postoperative urethral complications.Methods The data of 116 hypospadias patients underwent TIP urethroplasty performed by the same urologist in our hospital from January 2014 to December 2017 were retrospectively analyzed.The age of patients ranged from 0.5-15.4 years,with the median age of 1.5 years.Meatal location was distal in 47 (39.5％),midshaft in 62 (52.1％) and proximal in 10(8.4％) patients.Unhealthy urethral plate occurred in 49 (42.2％) patients.F8 catheter was used for urethroplasty in 92 (79.3 ％) patients,F10 in 17 (14.7％),and F12 in 7 (6.0％).According to the pattern of urinary diversion,patients were divided into two groups.Conventional catheter group in 56 patients (group A):the catheter was chosen in as large size as possible for urethroplasty without tension.Replace a smaller-size catheter group in 60 patients (group B):replace a smaller-size catheter after urethroplasty on the basis of group A.There were no statistically significant differences in age,meatal location and catheter size between the two groups (P ＞ 0.05).Results The mean follow up was 23 months (range 6-66 months).There were 73(62.9％) cases of orifice overflow during indwelling catheterization.There were 5 (4.3％) patients needed further reoperation result from postoperative urethral complications,including 4 cases of fistula and 1 case of meatal stenosis.The process of replacing a smaller-size catheter after urethroplasty in group B was simple and without adverse reactions.There were 15 (26.8％) cases of orifice overflow in group A and 58 (96.7％) in group B.There were statistically significant differences in orifice overflow between the two groups (P ＜ 0.05).There were 5 (8.9％) cases of postoperative urethral complications in group A and 0 case in group B.There were statistically significant differences in postoperative urethral complications (P ＜ 0.05).Conclusions The process of replacing a smaller-size catheter after TIP urethroplasty in was simple and subsequently contributed to less postoperative urethral complications.The results of replacing a smaller-size catheter after TIP urethroplasty were superior to that of no replacing conventionally.

Objective To investigate and analysis the clinical effect of pramipexole in Parkinson's disease with depression.Methods The patients with Parkinson disease patients with depression were selected in a total of 100 as the research object,and were randomly divided into two groups,the observation group and the control group with 50 cases in each group.The control group was taken conventional treatment,the observation group was given pramipexole based on the conventional treatment methods,the the effects of treatment were observed and compared. Results The MIHD score of the observation group after treated for 12 month (8.26 ±1.96)was lower than the score before treatment (24.91 ±4.6),and the score of the control group after treated for 12 month (11.15 ±2.10)was also lower than the score before treatment (24.48 ±5.34),the difference were all statistically significant(P<0.05). After treated for 12 month,the score in the observation group was lower than that in the control group,and the total effective rate in the two group were 94% and 80% respectively(P<0.05 ).The UPDRS score of the observation group was lower than in the control group,but the difference was not significant(χ2 =14.756,P<0.05).Conclusion Give pramipexole has notable curative effect on the depression disease in patients with Parkinson disease on the basis of conventional therapy method,and has the value of popularization.

This paper reports the diagnosis and therapy of one case of Dipylidium caninum infection in an infant.

Objective To investigate the roles of heavy metals in the onset of Alzheimer 's disease (AD) and vascular dementia (VaD) and to analyze the relationship between cognitive impairment and plasma heavy metal concentrations in patients with AD. Methods Fifty patients with AD, 20 with VaD, and 20 healthy controls were included in the study. According to the Clinical Dementia Rating (CDR), the AD patients were divided into mild dementia (CDR = 1 )and moderate to severe dementia (CDR = 2 to 3 ) groups. All the observational subjects performed the Mini-Mental State Examination (MMSE) score, Hachinski ischemic index score,and CDR score. A fasting venous blood sample was taken from all the subjects for detection of the heavy metal (Tu, Ca, Fe, Me, Zn, Hg, Cr, Co, Se, and Pb) concentrations at the same time.Results Compared to the control group, the plasma Cu concentration in the mild dementia and moderate to severe dementia groups increased significantly (0. 66 ± 0. 2 1, 0. 84 ± 1.11, and 0. 85 ± 1.12 ng/g, respectively (P ＜ 0. 05). There was no significant difference between the mild AD group and the moderate to severe dementia group. The Pb concentration in the control group was significantly lower than that in the moderate to severe dementia group (22.79 ±3.94 ng/gvs. 40. 82 ± 16.96 ng/g, P ＜ 0. 05 ). While there were no significant differences between the control and the mild dementia and moderate to severe dementia groups. The plasma Cu concentration (0.84 ± 1.25 ng/g vs. 0. 66 ± 0.21 ng/g, P ＜＜ 0. 05) and Pb concentration (32.42 ± 14. 12 ng/gvs. 22.79 ± 3.94 ng/g, P ＜ 0. 05) in the AD group were significantly higher than that in the control group. While there was no significant difference between the VaD group and the control group for metal concentrations. There was also no significant difference for metal concentrations hetween the VaD group and the AD group. Conclusions Some heavy metals, such as Cu and Pb might have participated in the pathogenic process of AD, but the heavy metal concentrations did not have close relationship with the onset of VaD. There was no significant correlation between the degree of cognitive impairment and the plasma metal concentrations in patients with AD.