Objective To compare the clinical effect of aripiprazole and risperidone in patients with schizophrenia and metabolic syndrome.Methods A retrospective analysis was performed on the case data of schizophrenia and metabolic syndrome.According to different treatment methods,they were divided into risperidone group(oral risperidone,2 mg once,twice a day)and aripiprazole group(oral aripiprazole,5 mg once,once a day).All were treated for 24 weeks and given lifestyle intervention.The clinical effect,scores of positive and negative symptom scale(PANSS),metabolic syndrome-related indexes[systolic blood pressure(SBP),diastolic blood pressure(DBP),body mass index(BMI),fasting blood glucose(FPG),triglyceride(TG)],cognitive function[MATRICS consensus cognitive battery(MCCB)],levels of serum brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB)and glial cell line-derived neurotrophic factor(GDNF)were compared between the two groups.The adverse drug reactions were statistically analyzed in two groups.Results There were 60 cases in risperidone group and 60 cases in aripiprazole group.The total response rates of aripiprazole group and risperidone group were 91.67％and 76.67％,with significant difference(P＜0.05).After treatment,scores of positive symptoms in PANSS in aripiprazole group and risperidone group were(10.04±1.55)and(11.52±1.62)points;negative symptom scores were(12.74±2.38)and(14.38±2.25)points;general psychopathology scores were(16.53±4.39)and(19.76±4.10)points;total scores of PANSS were(39.31±6.25)and(45.66±6.71)points;total scores of MCCB were(43.61±8.50)and(40.55±8.16)points;BMI were(24.05±2.52)and(25.73±2.86)kg·m-2;SBP were(123.61±7.64)and(128.75±8.59)mmHg;FPG were(5.69±0.60)and(6.38±0.62)mmol·L-1;TG levels were(1.76±0.20)and(2.01±0.22)mmol·L-1;levels of serum BDNF were(32.41±5.81)and(28.65±4.87)pg·mL-1;TrkB levels were(43.88±5.92)and(41.73±5.63)ng·mL-1;GDNF levels were(587.47±36.12)and(468.23±35.68)pg·mL-1,the differences between the two groups were all statistically significant(all P＜0.05).There was no significant difference in the incidence of adverse drug reactions between aripiprazole group and risperidone group(15.00％vs.6.67％,P＞0.05).Conclusion Compared with risperidone,clinical effect of aripiprazole is better in patients with schizophrenia and metabolic syndrome,which has fewer effects on body weight,blood pressure and glycolipid metabolism,and it may improve cognitive function by increasing levels of serum BDNF,TrkB and GDNF.

Objective To investigate the dosimetric difference between manual and inverse optimization in 3-dimensional (3D) brachytherapy for gynecologic tumors. Methods This retrospective study was conducted among a total of 110 patients with gynecologic tumors undergoing intracavitary combined with interstitial brachytherapy or interstitial brachytherapy. Based on the original images, the brachytherapy plans were optimized for each patient using Gro, IPSA1, IPSA2 (with increased volumetric dose limits on the basis of IPSA1) and HIPO algorithms. The dose-volume histogram (DVH) parameters of the clinical target volume (CTV) including V200, V150, V100, D90, D98 and CI, and the dosimetric parameters D2cc, D1cc, and D0.1cc for the bladder, rectum, and sigmoid colon were compared among the 4 plans. Results Among the 4 plans, Gro optimization took the longest time, followed by HIPO, IPSA2 and IPSA1 optimization. The mean D90, D98, and V100 of HIPO plans were significantly higher than those of Gro and IPSA plans, and D90 and V100 of IPSA1, IPSA2 and HIPO plans were higher than those of Gro plans (P<0.05), but the CI of the 4 plans were similar (P>0.05). For the organs at risk (OARs), the HIPO plan had the lowest D2cc of the bladder and rectum;the bladder absorbed dose of Gro plans were significantly greater than those of IPSA1 and HIPO (P<0.05). The D2cc and D1cc of the rectum in IPSA1, IPSA2 and HIPO plans were better than Gro (P<0.05). The D2cc and D1cc of the sigmoid colon did not differ significantly among the 4 plans. Conclusion Among the 4 algorithms, the HIPO algorithm can better improve dose coverage of the target and lower the radiation dose of the OARs, and is thus recommended for the initial plan optimization. Clinically, the combination of manual optimization can achieve more individualized dose distribution of the plan.

Objective To investigate the dosimetric difference between manual and inverse optimization in 3-dimensional (3D) brachytherapy for gynecologic tumors. Methods This retrospective study was conducted among a total of 110 patients with gynecologic tumors undergoing intracavitary combined with interstitial brachytherapy or interstitial brachytherapy. Based on the original images, the brachytherapy plans were optimized for each patient using Gro, IPSA1, IPSA2 (with increased volumetric dose limits on the basis of IPSA1) and HIPO algorithms. The dose-volume histogram (DVH) parameters of the clinical target volume (CTV) including V200, V150, V100, D90, D98 and CI, and the dosimetric parameters D2cc, D1cc, and D0.1cc for the bladder, rectum, and sigmoid colon were compared among the 4 plans. Results Among the 4 plans, Gro optimization took the longest time, followed by HIPO, IPSA2 and IPSA1 optimization. The mean D90, D98, and V100 of HIPO plans were significantly higher than those of Gro and IPSA plans, and D90 and V100 of IPSA1, IPSA2 and HIPO plans were higher than those of Gro plans (P<0.05), but the CI of the 4 plans were similar (P>0.05). For the organs at risk (OARs), the HIPO plan had the lowest D2cc of the bladder and rectum;the bladder absorbed dose of Gro plans were significantly greater than those of IPSA1 and HIPO (P<0.05). The D2cc and D1cc of the rectum in IPSA1, IPSA2 and HIPO plans were better than Gro (P<0.05). The D2cc and D1cc of the sigmoid colon did not differ significantly among the 4 plans. Conclusion Among the 4 algorithms, the HIPO algorithm can better improve dose coverage of the target and lower the radiation dose of the OARs, and is thus recommended for the initial plan optimization. Clinically, the combination of manual optimization can achieve more individualized dose distribution of the plan.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

p53 is an important tumor suppressor in the body,but research has found that p53 is one of the most frequent alterations in nearly half of human cancers.Mutant p53(mtp53)not only promotes tumor development but also serves as a pivotal factor in tumor immunity.Research has demonstrated that mtp53 participates in many aspects of tumor immune response through multiple mechanisms.We firstly describe the structure and function of mtp53,then the molecular mechanisms of mtp53 in tumor immuni-ty,including four aspects of promoting tumor immune escape,facilitating oxidative stress,regulating tumor-associated inflammatory signaling networks and tumor-infiltrating immune cell recruitment and dif-ferentiation.Finally,we summarize the effects of mtp53 on the immune micro-environment of lung canc-er,triple-negative breast cancer and colorectal cancer as well as the advances in the application of mtp53 in the treatment of cancers with PD-1/PD-L1 inhibitors,which may provide suitable directions and op-tions for the immunotherapy of mtp53-expressing cancers.

Objective:To establish reference ranges of central nervous system-related fetal intracranial markers during the first trimester in a local population of Suzhou.Methods:Ultrasound images of fetuses with normal birth outcomes in singleton pregnancies who underwent nuchal translucency(NT) screening during the first trimester (11-13 + 6 gestational weeks) from January 2021 to July 2022 at the Affiliated Suzhou Hospital of Nanjing Medical University were retrospectively selected. The images including 3 planes: the midsagittal plane of the fetal head, also known as the plane for NT measurement, the trans-ventricular plane of the fetal head, and the axial plane of the fetal head at the posterior fossa level. The brainstem (BS) thickness, brainstem to occipital bone distance (BSOB), the ratio of BS to BSOB (BS/BSOB), intracranial translucency (IT) thickness, cisterna magna (CM) width, and the midbrain (MB) to falx (F) ratio MB/F were measured in the mid-sagittal plane of the fetal head. Choroid plexus length (CPL) to occipital frontal diameter (OFD) ratio CPL/OFD, and choroid plexus area (CPA) to head area (HA) ratio CPA/HA were measured in the trans-ventricular plane of the fetal head. Anteroposterior diameter of the fourth ventricle (4V) and CM were measured in the axial plane of the fetal head at the posterior fossa level.Statistical analysis was performed to obtain the corresponding normal reference range.Intra-class correlation coefficient (ICC) was used to analyze intra-observer and inter-observer consistency. Pearson correlation analysis and linear correlation analysis were used to study the correlations between crown-lump length (CRL) and intracranial markers, and the regression equation was derived. Results:A total of 2 331 fetuses were enrolled, providing 1 023 images of the midsagittal plane, 817 images of the trans-ventricular plane, and 567 images of the axial plane of the fetal head at the posterior fossa level. The intra-observer and inter-observer ICCs of intracranial markers BS, BSOB, BS/BSOB, IT thickness, CM width, MB/F in the mid-sagittal plane, the intracranial markers CPL/OFD, CPA/HA on the trans-ventricular plane, and the intracranial markers 4V and CM width in the axial plane at the posterior fossa level were all >0.75. Fetal intracranial markers were linearly correlated with CRL. The midsagittal plane: BS, BSOB, BS/BSOB, IT thickness, CM width, MB/F were linearly correlated with CRL ( r=0.508, 0.626, -0.234, 0.105, 0.508, -0.493; all P<0.05); the trans-ventricular plane: CPL/OFD, CPA/HA were linearly correlated with CRL( r=-0.324, -0.268; all P<0.001); the axial plane of the fetal head at the posterior fossa level: 4V, CM width were linearly correlated with CRL ( r=0.246, 0.467; all P<0.001). Conclusions:Quantitative analysis of fetal intracranial markers in the first trimester is feasible. This study constructed a normal reference range of multiple intracranial markers related to central nervous system in the first trimester with a local population of Suzhou. And the construction of this normal range can provide an objective basis for the detection of fetal central nervous system malformations in the first trimester.

Tanshinones are one of the main effective components of Salvia miltiorrhiza, which play important roles in the treatment of cardiovascular diseases. Microbial heterogony production of tanshinones can provide a large number of raw materials for the production of traditional Chinese medicine(TCM) preparations containing S. miltiorrhiza, reduce the extraction cost, and relieve the pressure of clinical medication. The biosynthetic pathway of tanshinones contains multiple P450 enzymes, and the catalytic element with high efficiency is the basis of microbial production of tanshinones. In this study, the protein modification of CYP76AK1, a key P450-C20 hydroxylase in tanshinone pathway, was researched. The protein modeling methods SWISS-MODEL, Robetta, and AlphaFold2 were used, and the protein model was analyzed to obtain the reliable protein structure. The semi-rational design of mutant protein was carried out by molecular docking and homologous alignment. The key amino acid sites affecting the oxidation activity of CYP76AK1 were identified by molecular docking. The function of the obtained mutations was studied with yeast expression system, and the CYP76AK1 mutations with continuous oxidation function to 11-hydroxysugiol were obtained. Four key amino acid sites that affected the oxidation acti-vity were analyzed, and the reliability of three protein modeling methods was analyzed according to the mutation results. The effective protein modification sites of CYP76AK1 were reported for the first time in this study, which provides a catalytic element for different oxidation activities at C20 site for the study of the synthetic biology of tanshinones and lays a foundation for the analysis of the conti-nuous oxidation mechanism of P450-C20 modification.
Oxidoreductases ; Biosynthetic Pathways ; Molecular Docking Simulation ; Reproducibility of Results ; Salvia miltiorrhiza/chemistry* ; Amino Acids/metabolism* ; Plant Roots/genetics*

ObjectiveTo investigate the effects of epidural analgesia plus dexmedetomidine infusion on postpartum depression in parturients with natural childbirth. MethodsWe selected 70 parturients aged between 22 and 36， with singleton， term， cephalic presentation， natural delivery and ASA class I or Ⅱ. The cases undergoing epidural analgesia with ropivacaine and sufentanil were randomly divided into two groups by using a random number table （n=35 for each group）. The control group （Group C） used intravenous infusion of normal saline， while the experimental group （Group D） used equivalent volumes of intravenous infusion of dexmedetomidine. Participants were followed up at 1， 6， 12 weeks after childbirth to assess the severity of postpartum depression. Blood samples were collected at 12 h and 48 h after childbirth to measure the serum prolactin levels. The hemodynamic （HR and MAP） changes， VAS scores， and Ramsay scores were recorded at five time points： before analgesia （T1）， 10 min after analgesia （T2）， 30 min after analgesia （T3）， 12 h （T4） and 24 h （T5） after delivery. The number of analgesia pump presses and adverse events were also documented. ResultsCompared with Group C， Group D showed significantly lower EPDS scores at 1 week after childbirth， significantly higher prolactin concentrations at 12 h and 48 h after childbirth， significantly lower VAS scores at T2， T3 and T4， significantly higher Ramsay score at T3 and significantly reduced number of analgesia pump presses （P < 0.05）. ConclusionEpidural analgesia plus intravenous infusion of dexmedetomidine can alleviate early postpartum depression in women undergoing natural delivery， promote early prolactin secretion and provide a safe and effective adjunctive analgesic and sedative effect.

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

BACKGROUND: Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China. METHODS: Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders. RESULTS: During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HR = 0.78, 95% confidence interval [CI]: 0.71-0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m 2 ≤ BMI < 24.0 kg/m 2 ); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68-0.89) and 0.69 (95% CI: 0.59-0.79) compared with their counterparts, respectively. CONCLUSIONS High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.