Objective To explore the drug selection, usage, dosage and effect of clinical pharmacists in the treatment of secondary Candida bloodstream infection in patients with digestive tract perforation, and provide reference for rational clinical use of such anti-infection therapy. Methods During the treatment of Candida infection, anti-infection specialist clinical pharmacists suggested replacing fluconazole for anti-infection treatment, and adjusted the usage and dosage of caspofungin to ensure the application of full treatment course. Results The patient’s Candida bloodstream infection was effectively controlled. Conclusion Echininocandins such as caspofungin are the first choice for Candida infection. The maintenance dose should be reduced to 35 mg qd in patient with moderate liver function injury, and the anti-infection treatment should be done at least 14 days after the blood culture being negative. Clinical pharmacists participate in clinical pharmaceutical care practices such as clinical ward rounds, and actively assist doctors to develop individualized anti-infection programs, which could improve the level of clinical drug use and the clinical outcome of diseases.

Neurocutaneous syndrome is a multi-system disease involving the nervous system and skin,with onset in various forms and typically in infancy,which are difficult to cure with a poor prognosis.The etiology of neurocutaneous syn-drome is complex,mostly caused by gene mutations,including heritable mutations and occasionally non-hereditary postzy-gotic somatic mutations.Cases of different types of neurocutaneous syndrome have been reported,such as Sturge-Weber syndrome,tuberous sclerosis,and neurofibromatosis.Specific medications are lacking among current therapeutic ap-proaches including symptomatic treatment,drug therapy,chemoradiotherapy,surgery,and physical therapy.With the in-creasing understanding of the pathogenesis and progress in drug research and development,new drugs could be on the hori-zon.Remarkable evidence in the field of genetic diseases suggests that gene therapy may hold promise as a treatment for neurocutaneous syndrome through fixing the pathogenic gene defects.Considering the lack of systematic review on the rare and diverse conditions,we summarize relevant studies to provide a reference for clinical workers in the diagnosis and treat-ment of neurocutaneous syndrome.

Objectives:To search, evaluate, and summarize the evidence related to the application management of over-the-counter (OTC) medications for constipation in the elderly, providing evidence-based support for the rational use of these medications.Methods:A systematic search was conducted through computerized decision support systems, guideline websites, professional association websites, and databases for clinical decisions, guidelines, evidence summaries, and expert consensus on the management of OTC medications for constipation in the elderly. The search period spanned from January 2018 to March 2023. The quality of the literature was independently assessed, and evidence was extracted. The 2014 version of the Joanna Briggs Institute (JBI) evidence grading system was used to determine the levels of evidence.Results:A total of 18 article were included, consisting of two clinical decisions, five guidelines, seven expert consensus statements, and four evidence summaries. These covered five areas: medication principles for elderly individuals with different characteristics, medication selection, medication monitoring, health education, and precautions, culminating in a total of 30 best evidence.Conclusions:This study summarizes the best evidence for the management of OTC medications for constipation in the elderly, providing evidence-based support for the rational application of these medications.

Objective To observe the effect of Qixian Tongluo Formula on contralateral corticospinal tract(CST)remodeling and motor functional recovery in rats with cerebral infarction,and to explore its potential molecular mechanism from the perspective of regulating factors related to never remodeling.Methods The rat middle cerebral artery occlusion(MCAO)model was established by silk thread ligation.Fifty model rats were randomly divided into model group,citicoline group(0.054 g·kg-1),Qixian Tongluo Formula low-,medium-and high-dose(7.83,15.66,31.32 g·kg-1)groups,and sham operation group,with 10 rats in each group.The intervention administration was started on the 3rd day after operation once a day for 26 consecutive days.On the 3rd,14th and 28th day after operation,the gross motor function was evaluated by Longa score,and the fine motor function was evaluated by beam-walking test(BWT)score.The contralateral motor cortex was injected with the nerve tracer biotin dextran amine(BDA)on the 14 th day after operation to anterogradely trace the CST.On the 28th day after operation,the expression of axonal growth associated protein-43(GAP-43)and BDA positive fibers in the contralateral motor cortex and cervical spinal cord were detected by immunohistochemistry.The co-localization areas of BDA positive fibers and presynaptic marker protein vesicular glutamate transporter 1(VGLUT1)in the cervical spinal cord gray matter were detected by immunofluorescence.The expressions of brain-derived neurotrophic factor(BDNF),glial cell-derived neurotrophic factor(GDNF),nerve growth factor(NGF)and nerve remodeling-associated inhibitory factor[Nogo-A,oligodendrocyte myelin glycoprotein(OMgp)and myelin-associated glycoprotein(MAG)]in the contralateral motor cortex were detected by Western Blot.Pearson correlation analysis was used to analyze the correlation between Longa score or BWT score and BDA/VGLUT1 co-localization area,respectively.Results Compared with the sham operation group,rats in the model group had obvious symptoms of motor function deficits,and the Longa scores were significantly increased(P＜0.01)and the BWT scores were significantly decreased(P＜0.05,P＜0.01)at each time point.The expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was up-regulated(P＜0.05),the number of edge-crossing fibers from the posterior funiculus in cervical cord was increased(P＜0.05),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was increased(P＜0.05),the expressions of BDNF,GDNF and NGF in the contralateral motor cortex were up-regulated(P＜0.05),while the expressions of Nogo-A,OMgp and MAG were down-regulated(P＜0.05).Compared with the model group,the Longa scores in each administration group on the 14th and 28th day after MCAO operation were significantly decreased(P＜0.01),the BWT scores were significantly increased(P＜0.01),the expression of GAP-43 in the contralateral motor cortex and cervical spinal cord was significantly up-regulated(P＜0.01).The number of edge-crossing fibers from the posterior funiculus in cervical cord was significantly increased(P＜0.01),the co-localization area of BDA/VGLUT1 in the gray matter of the cervical spinal cord was significantly increased(P＜0.01).The expressions of BDNF,GDNF and NGF in the contralateral motor cortex were significantly up-regulated(P＜0.01,P＜0.05),while the expressions of Nogo-A,OMgp and MAG were significantly down-regulated(P＜0.05),and the most significant effect was observed in the high dose group.The Longa score was negatively correlated with the co-localization area of BDA/VGLUT1(r=-0.89,P＜0.01),and the BWT score was positively correlated with the co-localization area of BDA/VGLUT1(r=0.84,P＜0.01).Conclusion Qixian Tongluo Formula can improve motor function through promoting contralateral CST remodeling in MCAO rats after cerebral infarction,and the molecular mechanism may be related to the regulation of the expression of nerve remodeling-associated factor in the contralateral motor cortex.

This study explores the application effect of the case-based teaching method based on Xuexitong learning platform in the online teaching of Digestive System, and analyzes the learner's emotional experience, learning behavior, and learning effect in the case-based online teaching. The results of the study show that the case-based online teaching model based on Xuexitong learning platform improves students' online learning interest, and the students have good emotional experience, high learning enthusiasm, good classroom interaction, enhanced self-learning ability before and after class, and good learning effect. In addition, precise teaching can be used for individual students who are not enthusiastic about online learning.

Objective:To investigate the causes and prognosis of salvage cholecystectomy for relapsing cholecystolithiasis after gallbladder-preserving gall stones removal surgery.Methods:From Jul 2015 to Dec 2019, 24 referral patients with gallstone recurrence after gallbladder-preserving cholelithotomy surgery received salvage cholecystectomy. The clinical data was analyzed to explore the causes for re-operation and the prognosis.Results:Twenty-two cases had definite gallstone recurrence, among them 19 cases were symptomatic, 2 cases were operated on suspected gallbladder tumor and common bile duct stones induced acute cholangitis. Laparoscopic cholecystectomy was successfully performed in 23 cases and 1 case was converted to open surgery. No severe complication were observed in all the patients.Conclusions:Symptomatic gallstone recurrence is the most common causes of salvage cholecystectomy after gallbladder-preserving cholelithotomy. Laparoscopic surgery procedure is still highly successful.

ObjectiveTo investigate the effect of Zishen Huoxue prescription on promoting neurogenesis in hippocampal CA1 region of vascular dementia （VD） rats by regulating mitophagy. MethodThe 2-VO method was used to establish the VD rat model and 60 SD rats were randomly divided into sham operation group， model group， donepezil hydrochloride group， and Zishen Huoxue prescription low-dose（8.9 g·kg^-1）， medium-dose（17.8 g·kg^-1） and high-dose（35.6 g·kg^-1） groups. Morris water maze test was performed to detect the escape latency and the number of crossing platform in each group. The expression of phosphatase and tensin homology-induced kinase 1 （PINK1） and Parkinson protein （Parkin） mRNA in hippocampal CA1 region was detected by Real-time fluorescent quantitative polymerase chain reaction（Real-time PCR）. Western blot was used to determine the expression of mitochondrial autophagy signaling pathway-related proteins Parkin， prohibitin 2 （PHB2）， mitofusin 2 （Mfn2） and dynamin-related protein 1 （Drp1） in hippocampal CA1 region. The neurogenesis in hippocampal CA1 region was tested by Brdu method. ResultCompared with the conditions in the sham operation group， the learning and spatial memory abilities of the model group were decreased （P<0.05）， with damaged mitochondrial structure and autolysosome formation in the hippocampal CA1 region. The expressions of Parkin， Pink1 mRNA and Parkin， PHB2， and Drp1 proteins were up-regulated （P<0.05）， while the expression of Mfn2 protein and the neuronal regeneration in hippocampal CA1 region were reduced （P<0.05， P<0.05）. Compared with the conditions in the model group， Zishen Huoxue prescription enhanced the learning and spatial memory abilities of VD rats （P<0.05）， increased the number of autophagosomes in hippocampal CA1 region and improved the mitochondrial structure. The expression of Parkin， Pink1 mRNA and Parkin， PHB2， and Drp1 proteins in hippocampal CA1 region was up-regulated （P<0.05， P<0.01）while the expression of Mfn2 protein was down-regulated（P<0.05， P<0.01）. The number of new neurons in hippocampal CA1 region was also increased（P<0.05， P<0.01）. ConclusionThe promoting effect of Zishen Huoxue prescription on the neurogenesis in hippocampal CA1 region of VD rats was related to the mitophagy mediated by Pink1/Parkin signaling pathway.

Objective:To construct the evaluation index system of pediatric specialized nurses' core competence, so as to provide a basis for accurate measurement of pediatric specialized nurses' core competence.Methods:A research group was established in August 2021. Based on the quality onion model and literature analysis, a qualitative interview was conducted in September 2021 with 10 provincial and above hospitals pediatric specialist nurses, 5 pediatric nursing managers, 5 pediatric chief physicians and 5 primary caregivers for children selected by objective sampling. From September 2021 to February 2022, questionnaires were sent to 16 experts via email or WeChat for three rounds of Delphi expert consultation. The evaluation indexes of pediatric specialized nurses' core competence were determined according to the authority coefficient, Kendall coordination coefficient, coefficient of variation and other factors.Results:Among three rounds of expert consultation, the effective recovery rates of the questionnaire were all 100.00% (16/16) , and the authority coefficients were 0.813, 0.888 and 0.895, respectively, and the Kendall coordination coefficients were 0.175 (χ 2=289.348, P<0.01) , 0.239 (χ 2=408.131, P<0.01) and 0.288 (χ 2=467.280, P<0.01) , respectively. The final evaluation index system of pediatric specialized nurses' core competence included 6 first level indicators, 18 second level indicators and 84 third level indicators. Conclusions:The evaluation index system of pediatric specialized nurses' core competence is scientific and reliable, which can be used as an effective tool to measure the core competence of pediatric specialized nurses.

DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We reveal that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germ cell development, and the methylome of PGCs is reset to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When DNA methyltransferase (DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMT activity can prevent the female-to-male sex transition, sug-gesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germ cell development and sexual plasticity.

Objective To investigate the prevalence and risk factors of sarcopenia in peritoneal dialysis (PD) patients.Methods The patients who underwent regular peritoneal dialysis at Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine between November 2016 and March 2018 were enrolled.Handgrip strength (HGS) was measured to assess muscle strength.Bioelectrical impedance spectroscopy (BIS) was applied to measure the lean tissue index (LTI).Reduced LTI plus decreased HGS was defined as sarcopenia.The prevalence of sarcopenia in PD patients was evaluated.According to the presence or absence of sarcopenia,they were divided into the sarcopenia group and the non-sarcopenia group,and the differences in clinical indicators between the two groups were compared.Multivariate logistic regression was used to explore the risk factors of sarcopenia in PD patients.Results A total of 207 patients were enrolled in the study with age of (55.3±13.7) years and a median PD duration of 22.9(7.3,60.9) months.Of them,122 patients (58.9％) were male,45 patients (21.7％) had diabetics and 32 patients (15.5％) suffered from cardiovascular diseases.There were 27 patients (13.0％) diagnosed with sarcopenia.These patients presented with longer PD duration,more prevalent diabetics,lower residual renal function (RRF) and serum pre-albumin,greater ratio of extracellular water to intracellular water (ECW/ICW) and high sensitive C-reactive protein in contrast with those in the non-sarcopenia group (all P ＜ 0.05).Multivariate logistic analysis showed that male (OR=3.94,95％ CI 1.35-11.50,P=0.O12),longer PD duration (OR=1.01,95％CI 1.00-1.02,P=0.029) and higher ECW/ICW (OR=1.09,95％CI 1.05-1.14,P ＜ 0.001) were independent risk factors of sarcopenia in PD patients.Conclusions Sarcopenia is common in PD patients.Male,longer PD duration and higher ECW/ICW were independent risk factors of sarcopenia in PD patients.