ObjectiveTo investigate the effects of jujuboside A （JuA） on the learning and memory abilities and histopathological changes in the rat model of vascular cognitive impairment （VCI） and explore the potential mechanisms by which JuA treats VCI. MethodsA total of 50 male SPF-grade SD rats were randomized into a sham operation group （n=10）， a blank control group （n=10）， and a modeling group （n=30）. The rats in the modeling group underwent bilateral carotid artery ligation （2-VO） for the modeling of VCI. After stabilization， the VCI rats were randomized into model， JuA （20 mg·kg^-¹）， and donepezil （0.45 mg·kg^-¹） groups. After 4 weeks of gavage， the novel object recognition and Morris water maze tests were conducted to evaluate the learning and memory abilities of rats. Nissl staining was employed to evaluate the morphology and number of hippocampal neurons. Real-time PCR was employed to measure the mRNA levels of glycogen synthase kinase-3β （GSK-3β）， cAMP response element-binding protein （CREB）， B cell lymphoma-2 （Bcl-2）， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the hippocampal tissue. Western blot was employed to quantify the protein levels of GSK-3β， p-GSK-3β， p-CREB， Bcl-2， PI3K， p-PI3K， Akt， and p-Akt in the hippocampal tissue. ResultCompared with the sham operation group， the model group exhibited declines in the learning and memory abilities （P<0.01）， neuronal damage and decreased neurons in the hippocampal CA1 region （P<0.01）， up-regulation in the mRNA level of GSK-3β （P<0.01）， and down-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2， as well as the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.01）. In comparison to the model group， both the JuA and donepezil groups demonstrated improvements in the learning and memory abilities （P<0.05， P<0.01）， with reduced neuronal damage and increased neurons （P<0.05， P<0.01）. In addition， the two groups showed down-regulation in the mRNA level of GSK-3β （P<0.01） and up-regulation in the mRNA levels of PI3K， Akt， CREB， and Bcl-2 and the protein levels of p-PI3K， p-Akt， p-GSK-3β， p-CREB， and Bcl-2 （P<0.05， P<0.01）. There were no statistically significant differences between the blank control and sham operation groups in terms of the learning and memory abilities， neuron count， and mRNA and protein levels of PI3K/Akt/GSK-3β pathway-related factors. ConclusionJuA can ameliorate the cognitive impairment in the rat model of VCI by activating the PI3K/Akt signaling pathway， reducing the apoptosis of hippocampal neurons， and alleviating the hippocampal neuronal damage.

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl₂ at designed doses (0, 0.5, 1.0, and 1.5 μmol·L⁻¹). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L⁻¹ dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.

Objective:To study the influence of different feeding patterns on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with high viral loads who received antiviral medication during pregnancy to the day of delivery.Methods:This prospective cohort study was conducted in Beijing You'an Hospital. From January 1, 2019, to March 31, 2020, and 574 pregnant women with positive hepatitis B surface antigen (HBsAg) and HBV DNA>2×10 5 IU/ml were enrolled. All participants received tenofovir, telbivudine, lamivudine, or propofol tenofovir from 24-28 weeks of gestation and discontinued on the day of delivery, and their neonates were postnatally given routine passive-active immunoprophylaxis. Based on the feeding patterns, the subjects were divided into three groups: breastfeeding ( n=257), bottle-feeding ( n=241) and mixed feeding groups ( n=76). The follow-up data were obtained from liver functions and HBV DNA level of the mothers at 6-8 weeks postpartum and HBV serological markers of infants at 7-12 months. One-way ANOVA, Student-Newman-Keuls, Chi-square test or Fisher exact test, and repeated measures ANOVA were used to analyze the data. Results:The average maternal HBV DNA levels before antiviral treatment did not differ significantly between the three groups [(7.90±0.67), (7.82±0.70), (7.83±0.70) log 10 IU/ml, F=0.912, P>0.05]. HBV DNA level before delivery in the mixed feeding group was slightly lower than that in the breastfeeding and bottle-feeding group [(3.87 ±1.08) vs (4.21±1.17) and (4.30±1.28) log 10 IU/ml, q= 3.052 and 3.831, both P<0.05], while the comparison between the latter two groups showed no significant differences ( P>0.05). After delivery, HBV DNA level in the bottle-feeding group was slightly lower than that in the breastfeeding group [(7.42±0.93) vs (7.69±0.90) log 10 IU/ml, q=4.583, P<0.05]. Among 580 infants (including six pairs of twins), only one bottle-fed infant (0.4%, 1/243) was infected with HBV through MTCT, and none in the breastfeeding or mixed feeding group ( P=0.553). Conclusions:For pregnant women with high viral loads of HBV who have received antiviral medication during pregnancy, although HBV DNA level will rebound after discontinuation upon delivery, breastfeeding is recommended considering it does not increase the risk of MTCT.

Objective:This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) patients. Methods:This prospective, single-arm, and open clinical study enrolled 30 adult Ph + ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results:All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS ( P=0.004) , HRFS ( P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS ( P=0.030) and EFS ( P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions:The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph + ALL patients. Clinical trial registration:ClinicalTrials.gov, NCT02523976.

OBJECTIVE：To investigate the accessibility of antibiotics in essential medicine list in medical institutions of Nanjing area ，and to provide reference for formulating and improving related drug policy. METHODS ：Taking the original and imitated drugs as the objects of investigation ，the standard investigation method jointly formulated by WHO/HAI was adopted to select 35 kinds of antibiotics which were included in Essential Medicine List （2018 edition）and International Drug Price Indicator Guide（2015 edition），and to investigate 3 dimenions such as the availability （proportion of institutions that could provide this drug），price（calculated by MPR ）and affordability （the ratio of drug expenditure to the daily minimum wage of non-technical government workers ）of them in 13 second-class or above medical institutions in Nanjing area by online questionnaires during Jan.-Jun. 2019，so as to put forward the suggestions for drug policy formulation. RESULTS ：The median availability of original drugs was 0，with a range of 0 to 100％；the median availability of generic drugs was 30.80％，with a range of 0 to 100％. The median MPR of original drugs was 5.54，with a range of 1.96 to 18.83；the median MPR of generic drugs was 1.76，with a range of 0.16 to 7.66. Median affordability of original drugs was 8.68，with a range of 1.19 to 41.79；the median affordability of generic drugs was 0.52， with a range of 0.03 to 16.80. CONCLUSIONS：Generic drugs are more available than the originals. The price of original drugs is generally very high ， while the price of generic drugs is mostly cheaper. The affordability of original drugs is really poor ， and the 规。E-mail：shaorong118@163.com affordability of generic drugs is totally good. There are stillrooms for further improvement in the overall accessibility of essential medicines. At present ，ensuring the accessibility of original drugs may be more helpful to meet the needs of treatment. It is suggested to update and adjust the essential medicine list based on the clinical medication requirement ，popularize the knowledge about essential medicines ，properly adjust the price of original drugs and ease the treatment burden of patient. It is supposed to take into full consideration about the regional factors and the needs of different medical institutions when making drug policy.

Objective:To analyze the clinical and immunological characteristics of a patient with activated phosphoinositide 3-kinase δ syndrome 2 (APDS2).Methods:A retrospective analysis of clinical data, immune-related gene sequencing, imaging and laboratory findings of a patient with APDS2 admitted to Children′s Hospital of Chongqing Medical University was performed. The absolute and relative numbers of peripheral lymphocyte subsets, immune cell subsets and phenotypes were detected by flow cytometry with the age matched healthy child or the patient's father as a control.Results:A female patient aged 6 years and 4 months old was firstly admitted due to paleness over one month and cough for 7 days in June 2017. The IgA (<0.067 g/L) decreased while the IgM (2.55 g/L) increased. The abdominal ultrasound found hepatomegaly (subcostal 1.7 cm) and splenomegaly (subcostal 3.6 cm), and gene sequencing revealed a heterozygous mutation in the PIK3R1 gene c.1425+1G>A. After the treatment with prednisone which was initiated with a dose of 10 mg/times, 3 times/d and continued and tapered over 7 months, the IgM decreased to normal (1.72 g/L), and the hepatomegaly (subcostal 0 cm) and splenomegaly (subcostal 0.5 cm) were improved. The patient was readmitted due to pale and sallow complexion for half a month in July 2019. The percentage of naive CD4 +T (0.386) and naive CD8 +T cells (0.271) were decreased while the percentage of terminally differentiated effector memory CD8 +T cells (0.377) and transitional B cells (0.223) were increased. The mean fluorescence intensity (MFI) of phosphorylated protein kinase B (AKT) in CD3 +T, CD4 +T and CD8 +T cells were higher in the patient (4 125, 5 213, 3 497) than those in her father (3 434, 3 312, 3 058). The percentage of follicular helper T cell (Tfh) (0.299), Th1 (0.491) and Th1-like cells (0.438) in the patient were higher than those in the healthy control (0.156,0.313,0.303), while the percentage of Th17 (0.126) and Th17-like cells (0.188) were lower than those in the healthy control (0.198, 0.315). And the percentage of CD57 in the patient (0.306) was also higher than that in the healthy control (0.246). Conclusions:The humoral immunity and cellular immunity of APDS2 patient are impaired to varying degrees. The steroid can improve the lymphoproliferation and autoimmune hemolytic anemia in this case.

Gingival recession is one of the common oral symptoms. Periodontal soft tissue defects caused by gingival recession and problems related to aesthetics, prosthetics and orthodontic treatment have garnered increasing attention. This article reviews the etiology, classification and treatment of gingival recession to provide a reference for the diagnosis and treatment of gingival recession. Anatomical characteristics of teeth, bacterial and viral infection, Occlusion trauma, Improperbrushing methods and other daily behaviors and iatrogenic factors may lead to gingival recession. Miller classification is the most commonly used classification standard. It is divided into 4 degrees according to the relationship between gingival recession and the association between the gingival membrane and the loss of adjacent alveolar bone or interdental papilla. Gingival surgeries, such as coronally advanced flap, laterally positioned flap, subepithelial connective tissue graft for Miller Ⅰ degrees and Ⅱ gingival recession retreat, obtain a more satisfactory success rate. Regarding the Ⅲ degree gingival recession, the postoperative curative effect is poor and can only cover part of the root. Regarding Ⅳ degrees gingival recession, surgery cannot reach the root surface coverage. For patients with Miller Ⅳgingival recession caused by severe periodontitis, the surgical treatment is poor, and repair methods, such as sputum, can also be considered. In recent years, a variety of biological materials have been jointly applied to gingival surgery, such as tooth enamel matrix derivative (EMD), allograft acellular dermal matrix (ADM), porcine collagen matrix (PCM) and platelet-rich fibrin (PRF). The use of these biomaterials can improve root coverage, increase gingival thickness and keratinized gingival width, avoid the requirement of palatal flap removal, reduce the surgical risk and increase patient compliance.

OBJECTIVE:To provide reference for reducing the clinical return of finished infusions. METHODS:Interventions for clinical return of PIVAS finished infusions in our hospital were introduced,the return situation of finished infusions before(dur-ing 2013-2014)and after(during 2015-2016)intervention was compared,and intervention effects were evaluated. RESULTS:Our hospital intervened it by rationally selecting and using syringes,strengthening visible particle check of finished infusion before dis-tribution;optimizing the order of drug configuration,reasonably arranging the drug infusion sequence;strengthening the clean-up in work area before drug infusion,correctly using disinfectant;strictly implementing intravenous infusion associative operation, playing the role of pharmacists;cultivating good work habits,and strengthening teamwork,etc. Compared with before interven-tion,the return numbers of finished infusion were decreased by 41.2%,and reported loss amount reduced by 45.7%. The return caused by visibility particles,finished infusion oxidation discoloration after too long storage time,finished infusion leakage,contin-uous infusion of drugs compatibility,heterodyne error,improper drug configuration method in packaging to the ward,improper use of disinfectant before infusion decreased by 25.3%,46.9%,39.4%,77.8%,73.9%,75.0%,100%,respectively. CONCLU-SIONS:Intervening the return of finished infusion can reduce the return numbers and drug waste.

BACKGROUND:In recent years, based on high-throughput molecular imaging, integration of genomics, proteomics and computer aided design and the application of correlative “technical chains” have achieved great achievements in the research of breast cancer, lung cancer, gastric cancer, colon cancer, ovarian cancer and melanin tumor. However, there are few researches on oral squamous cel carcinoma. OBJECTIVE:To detect the gene expression profile of the oral squamous cel carcinoma tissue and normal paracarcinoma tissue using DNA chip-based gene expression profile. METHODS:Two samples of oral squamous cel carcinoma tissue and normal paracarcinoma tissue of patients who received treatment at Stomatological Hospital of Guangdong Province of China in 2013 were included in this study. The gene expression profiles of oral squamous cel carcinoma and normal paracarcinoma tissue were determined by the Roche NimbleGen gene expression microarrays. RESULTS AND CONCLUSION: According to screening criteria of differential genes, 7 872 out of 32 448 detected genes were differentialy expressed genes of oral squamous cel carcinoma, which accounts for 24% of the total number of the screening genes. 3 800 genes were up-regulated, and 4 072 were down-regulated. The results confirm that through detection with the help of gene expression profile clip, 7 872 differentialy expressed genes were obtained through DNA chip-based gene expression profiles according to the screening criteria. Thus it can be concluded that the occurrence and development of the tumors are not a result of single or several genes. Previous experiments based on a single or several genes have great limitations. These findings also suggest that the occurrence of tumor is a result of mutual regulatory effects of many genes forming a network, moreover, the interactions of the network is quite complicated.

Objective: To summarize the experience of clinical pharmacy of traditional Chinese medicine in a special hospital. Methods: Combining the work of clinical pharmacists in the hospital, the service content of clinical pharmacy of traditional Chinese medicine in the special hospital was described and the improvement methods were explored. Results:The pharmaceutical care of clini-cal pharmacy of traditional Chinese medicine could improve safe and rational use of drugs. Conclusion: Pharmacists should enhance the study of pharmacy and traditional Chinese medicine to improve the pharmaceutical care of clinical pharmacy of traditional Chinese medicine.