This paper aims to study the effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress(CUMS)-induced depression-like and insomnia behavior models of mice. The CUMS-induced depression-like and insomnia behavior model of mice was established by CUMS treatment for three weeks. The mice were randomly divided into control group, model group, positive drug diazepam group(2 mg·kg~(-1)), as well as low-dose group(1.95 g·kg~(-1)), medium-dose group(3.9 g·kg~(-1)), and high-dose group(7.8 g·kg~(-1)) of Ziziphi Spinosae Semen extracts, with 18 mice in each group. On the 15th day of modeling, the drug was administered intragastrically once a day for one week. Then, the pentobarbital sodium cooperative righting experiment, open field experiment, and elevated plus maze experiment were carried out, respectively. The contents of neurotransmitters 5-hydroxytryptamine(5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) in serum and thalamus of mice, as well as the levels of corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) in serum, were determined by enzyme-linked immunosorbent assay(ELISA). The neuron damage in the hippocampus of mice was observed by hematoxylin-eosin(HE) staining and Nissl staining. Western blot was used to detect the expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), monoamine oxidase A(MAOA), five prime repressors under dual repression binding protein 1(Freud1), synaptic plasticity-related proteins [cellular gene FOS(C-FOS), postsynaptic density protein 95(PSD95), synapsin 1(SYN1), and activity-regulated cytoskeleton-associated gene(ARC)], blood-brain barrier(BBB) permeability-related proteins [zonula occludens 1(ZO-1), occludin, and claudin 1], inflammatory factors [NOD-, LRR-and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), gasdermin D(GSDMD), caspase-3, and caspase-8], and antioxidant factors [nuclear factor erythroid 2-related factor 2(NRF2) and heme oxygenase 1(HO1)] in thalamic tissue of mice. The results indicated that compared with that in the model group, the sleep latency was significantly shortened, and the sleep duration was significantly prolonged in each dose group of Ziziphi Spinosae Semen extracts. The number of visits to the central area of the open field and the distance and time of visits were significantly increased in each dose group of Ziziphi Spinosae Semen extracts. In addition, the proportion of distance and time of entering the open arm area of the elevated plus maze was significantly increased in each dose group of Ziziphi Spinosae Semen extracts. The contents of 5-HT and 5-HIAA in serum and thalamus of mice increased to varying degrees in each dose group of Ziziphi Spinosae Semen extracts; the contents of CRH, ACTH, and CORT in serum of mice were significantly decreased. The protein expression of TPH2 was significantly increased. The protein expression of MAOA, SERT, and Freud1 was significantly decreased. Ziziphi Spinosae Semen extracts could also significantly reduce the protein expression of C-FOS but significantly increase the protein expression of PSD95, ARC, and SYN1. They could reduce the pathological damage of the hippocampus in mice and significantly increase the protein expression of ZO-1, occluding, and claudin 1. The protein expression of NLRP3, GSDMD, ASC, caspase-3, and caspase-8 in the thalamic tissue of mice was significantly decreased, and the protein expression of HO1 and NRF2 was significantly increased. In conclusion, Ziziphi Spinosae Semen extracts could effectively improve sleep disorders and depression-like behaviors in CUMS-induced model mice, which may be related to regulating the 5-HT anabolism process and hypothalamic-pituitary-adrenal(HPA) axis-related hormone levels, reducing pathological damage in the hippocampus, improving synaptic plasticity, repairing BBB integrity, and alleviating inflammatory response and oxidative stress damage.
Animals ; Ziziphus/chemistry* ; Mice ; Male ; Depression/psychology* ; Drugs, Chinese Herbal/administration & dosage* ; Sleep Initiation and Maintenance Disorders/psychology* ; Stress, Psychological/complications* ; Behavior, Animal/drug effects* ; Humans ; Disease Models, Animal

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective To analyze the monitoring data of Oncomelania hupensis in the national schistosomiasis surveillance sites of China from 2015 to 2019, so as to understand the changes of Oncomelania snail status in the schistosomiasis-endemic areas of China and to provide the scientific evidence for Oncomelania snail control. Methods According to the requirements of National Scheme for Schistosomiasis Surveillance in China (2014 Edition), national schistosomiasis surveillance sites were assigned in all schistosomiasis-endemic counties (cities, districts) and the potential endemic counties (cities, districts) in the Three Gorges Reservoir areas, and Oncomelania snail status was monitored according to different epidemic types. In endemic areas, Oncomelania snail survey was performed by means of systematic sampling and environmental sampling, and the occurrence of frames with Oncomelania snails and the prevalence of Schistosoma japonicum infections in Oncomelania snails were calculated, while in potential endemic areas, the risk of imported Oncomelania snails and Oncomelania snails in floating debris were monitored. Results Oncomelania snail survey was performed covering an area of 116 834.16 hm² in the national schistosomiasis surveillance of China from 2015 to 2019, with 35 007.62 hm² Oncomelania snail habitats identified. A total of 6 908 292 frames were surveyed during the 5-year period, and there were 364 555 frames detected with Oncomelania snails, with a 5.28% mean occurrence of frames with Oncomelania snails. Among 997 508 living Oncomelania snails captured, no S. japonicum infections were detected, and loop-mediated isothermal amplification (LAMP) assay detected 18 positive mixed Oncomelania snail samples. During the period from 2015 to 2019, 147.20 hm² emerging Oncomelania snail habitats were identified, with an overall tendency towards a rise seen in the proportion of emerging Oncomelania snail habitats in plain regions with waterway networks (0.12% to 92.00%), a tendency towards a rise followed by decline seen in marshland and lake regions (0 to 96.72%), and a large fluctuation in hilly regions (0 to 88.49%). A total of 831.10 hm² re-emerging Oncomelania snail habitats were found in the national schistosomiasis surveillance sites of China from 2015 to 2019, with an overall tendency towards a rise seen in the proportion of re-emerging Oncomelania snail habitats in marshland and lake regions (16.05% to 79.66%), an overall tendency towards a decline seen in hilly regions (19.25% to 81.00%), and a minor fluctuation in plain regions with waterway networks (1.10% to 10.14%). During the 5-year period from 2015 to 2019, a total of 48 656 kg floating debris were captured in 4 surveillance sites in the Three Gorges Reservoir areas, and 2 204 snails were found, with no Oncomelania snails identified. Conclusions The areas of Oncomelania snail habitats tended to be stable in the national schistosomiasis surveillance sites of China during the period from 2015 to 2019, however, there was a gradual rise in the area of Oncomelania snail habitats year by year, and LAMP assay identified positive Oncomelania snail samples, suggesting Oncomelania snail control is far from optimistic in China.

OBJECTIVE: To explore the prognostic factors of young and middle-aged patients with acute myeloid leukemia (AML) and the predictive value of minimal residual disease (MRD) before consolidation therapy. METHODS: The clinical data of 262 middle-risk young and middle-aged patients with AML treated in our hospital from January 2010 to December 2018 were selected retrospectively. All the patients were reached morphological leukemia-free state (MLFS) after induction chemotherapy, the overall and subgroup clinical data of the selected patients were analyzed. Cox regression model was used to evaluate the independent prognostic factors of middle-risk newly diagnosed young and middle-aged patients. RESULTS: Among the patients less than 40 years old treated by consolidation therapy with PR-CT and allo-HSCT regimens, the 5-year cumulative leukemia-free survival(LFS) rates were 40.92% and 63.51%（P=0.01）respectively, while those over 40 years old were 23.61% and 49.14%（P=0.00）, respectively. The 5-year cumulative LFS rates of the patients treated by chemotherapy and achieved early remission and late remission were 63.51% and 41.33% （P=0.01）, respectively. The 5-year cumulative overall survival(OS) rates of the patients treated by PR-CT and allo-HSCT regimens were 23.65% and 69.32% (P=0.00), respectively, and the 5-year cumulative LFS rates were 26.44% and 52.30% (P=0.01). Among the patients treated by PR-CT consolidation treatment, the MRD-negative and MRD-positive cases were 74 and 60 cases, respectively. The 5-year cumulative incidence of relapse rate in the MRD-negative subgroup was significantly lower than those in the MRD-positive subgroup (P<0.05), the 5-year LFS rate and OS rate of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). For the patients treated by allo-HSCT consolidation treatment, the MRD-negative and MRD-positive cases were 66 and 62 cases, respectively. The 5-year cumulative incidence of relapse rate of the patients in MRD-negative subgroup was significantly lower than those in MRD-positive subgroup（P<0.05）, and the 5-year LFS and OS rates of the patients in MRD-negative subgroup were significantly higher than those in MRD-positive subgroup (P<0.05). The univariate analysis results showed that age, chromosome karyotype, MRD status after reaching MLFS, and consolidation treatment regime were all related to the prognosis of patients (P<0.05). The multivariate analysis results showed that age, MRD status after reaching MLFS, and consolidation therapy were the independent factors affecting the cumulative OS rate of the patients (P<0.05). Chromosome karyotype was an independent factor affecting the cumulative LFS rate of the patients (P<0.05). MRD status and consolidation treatment plan after reaching MLFS were the independent factors affecting the cumulative recurrence rate of the patients (P<0.05). CONCLUSION The OS rate of middle-risk young and middle-aged patients with newly diagnosed AML is independently related to age, MRD status after MLFS and consolidation therapy, while chromosome karyotype is independently related to cumulative LFS, and allo-HSCT consolidation therapy is recommended for middle-risk young and middle-aged AML patients after induction chemotherapy for MLFS, especially for those less than 40 years old and MRD positive before consolidation therapy.
Adult ; Consolidation Chemotherapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Middle Aged ; Neoplasm, Residual ; Prognosis ; Retrospective Studies

Ischemic heart diseases are one of the major causes of death worldwide. Effective restoration of blood flow can significantly improve patients’ quality of life and reduce mortality. However, reperfusion injury cannot be ignored. Flavonoids possess well-established antioxidant properties; They also have other benefits that may be relevant for ameliorating myocardial ischemia-reperfusion injury (MIRI). In this review, we focus on flavonoids with cardiovascular-protection function and emphasize their pharmacological effects. The main mechanisms of flavonoid pharmacological activities against MIRI involve the following aspects: a) antioxidant, b) anti-inflammatory, c) anti-platelet aggregation, d) anti-apoptosis, and e) myocardial-function regulation activities. We also summarized the effectiveness of flavonoids for MIRI.

BACKGROUND: The persistence of bone atrophy and maxillary sinus gasification can cause a deficiency in the height of maxillary posterior teeth. It is very difficult to place dental implants at this site. Increasing bone mass in the maxilla is beneficial for dental implantation, and it is a currently accepted method to lift the maxillary sinus to compensate for bone loss. OBJECTIVE: To analyze the application effect of bone graft material, human working bone material and tissue engineering scaffold material in maxillary sinus elevation. METHODS: "Maxillary sinus elevation, dental implant, autologous bone, allograft, artificial bone, scaffold" were used as the key words in Chinese and English to retrieve relevant articles concerning materials used in maxillary sinus elevation included in PubMed and WanFang. Then, we analyzed the effects of different bone grafting materials on new bone formation, implant stability and bone-implant binding rate after maxillary sinus elevation. RESULTS AND CONCLUSION: Autologous bone is the gold standard of bone graft material in maxillary sinus elevation, which can ensure the bone mass and the long-term stability of implantation around the implant, but it is easy to cause secondary damage to the donor area and to produce infection. Allogeneic bone can be used as an alternative material of autogenous bone,such as deproteinized bovine bone minerals,inorganic bovine bone,etc.,which can generate new bone and ensure dental implantation to achieve sufficient stability. Artificial bone materials such as hydroxyapatite, beta-tricalcium phosphate,biphasic calcium phosphate compound,etc.have good bone conduction and can achieve a high bone-implant contact rate. Tissue-engineered bone grafts that can combine stem cells and cytokines with bio-scaffolds for maxillary sinus elevation can promote new bone formation, increase bone mass, and ensure dental implantation to achieve good stability.

This report presents the endemic status of schistosomiasis in the People's Republic of China at national level in 2016,and analyzes the data collected from the national schistosomiasis prevention and control system and 454 national schisto-somiasis surveillance sites. Among the 12 provinces(municipality and autonomous region)of endemic of schistosomiasis japoni-ca in P. R. China,5 provinces (municipality and autonomous region),i. e.,Shanghai,Zhejiang,Fujian,Guangdong and Guangxi,had achieved elimination,and 7 provinces of Sichuan,Yunnan,Jiangsu,Hubei,Anhui,Jiangxi and Hunan had achieved transmission control by the end of 2016. There are 451 endemic counties(cities,districts)covering 257 million peo-ple,specifically including 29692 endemic villages of 69.39 million people at risk. Among the 451 endemic counties(cities,dis-tricts),35.25％(159/451),42.35％(191/451)and 22.39％(101/451)reached the criteria of elimination,transmission inter-ruption and transmission control,respectively in 2016. By the end of 2016,it was estimated of 54454 infections of schistosome, decreased by 29.46％compared with 77194 in 2015. No acute schistosomiasis case was reported in 2016. There were 30573 ad-vanced schistosomiasis cases documented in 2016. A total of 8500710 individuals received schistosomiasis examinations and 600 individuals were parasitologically diagnosed,decreased by 83.36％compared with 3606 in 2015. The Oncomelania hupen-sis snail survey was performed in 22140 endemic villages and O. hupensis snails were found in 7106 villages,accounting for 32.109％of the total villages,with 20 newly detected villages with snails. The snail survey covered area of 813963.91 hm2 and snails were found in an area of 235096.04 hm2,including a newly detected area of 1346.48 hm2. No schistosome-infected snails were found in 2016. A total of 881050 bovines were raised in the schistosomiasis endemic area. Of them,510468 bovines re-ceived examinations,resulting in 8 schistosome-infected bovines. There were 147642 schistosomiasis cases receiving drug treat-ment in 2016,with 2303555 individuals undergoing expanded chemotherapy;there were 9 bovines with schistosomiasis receiv-ing drug treatment,with 439857 bovines undergoing expanded chemotherapy;a total of 139483.84 hm2 area with snail control by using molluscicides,with actual molluscicide-treated area of 73941.75 hm2;and 3101.52 hm2 snail habitants were treated by environmental modification. Based on the data from the 454 national schistosomiasis surveillance sites,the mean Schistosoma japonicum infection rate was 0.02％ and 0.0078％ in humans and bovines,respectively. No schistosome-infected snails were found in all the surveillance sites. The results demonstrate a decline in the endemicity of schistosomiasis in P. R. China com-pared with the level of 2015. However,the distribution area of snails in China is still large and the infection source of schistoso-miasis still exists to some extent in some endemic areas;in some regions,the task to reach the standard of transmission interrup-tion is still arduous. There are still objective factors of epidemic and transmission and risk factors of endemic reversal and re-bound for schistosomiasis. So,further control and effective surveillance as well as accurate prevention and control should be im-plemented to promote the elimination process on schistosomiasis in P. R. China.

Objective To analyze the genetic etiology of lateral ventriculomegaly fetal on the genome-wide level with chromosomal microarray analysis (CMA),and investigate the relationship between copy number variations (CNVs) and lateral ventriculomegaly and the application value of CMA in prenatal diagnosis of fetuses with lateral ventriculomegaly.Methods Seventy fetuses with lateral ventriculomegaly but normal or uncertain karyotype were selected and invasive prenatal diagnosis was performed in Xi Jing Hospital of the Fourth Military Medical University from Jan.2015 to Nov.2016.Microarray testing was performed using Affymetrix CytoScanTM 750k arrays and the results were analyzed according to biological information science database.The fetal development was regularly inspected,and follow up was conducted to find out the pregnancy outcome and fetal postnatal conditions.Results In 70 cases of lateral ventriculomegaly fetuses,there were 9 fetuses with pathogenic copy number variations (CNVs),3 fetuses with likely pathogenic CNVs and 1 fetus with likely pathogenic 1 oss of heterozygosity (LOH).During the 70 fetuses with lateral ventriculomegaly,2 pathogenic CNVs were detected in 6 fetuses with severe and non isolated lateral ventriculomegaly (33.3％).Pathogenic CNVs was not detected but 1 likely pathogenic CNV was detected in 3 fetuses with severe and isolated lateral ventriculomegaly (33.3％).Six pathogenic CNVs were detected in 31 mild and non isolated lateral ventriculomegaly (19.4％),and 2 likely pathogenic CNVs were also detected in these group (6.5％).One pathogenic CNV and 1 likely pathogenic CNV were detected in 30 fetuses with mild and isolated fetal lateral ventriculomegaly.Conclusions CMA can identify chromosome abnormality microdeletion/microduplication which was unrecognizable by conventional karyotyping analysis.The application of CMA may increase the detection rate of pathogenic CNVs in fetuses with lateral ventriculomegaly,and benefit evaluation of fetal prognosis in prenatal genetic counselling.

OBJECTIVETo observe the changes in Aβ40, Aβ42 and ADDLs in brains of 3 month-old APPswe/PS1dE9 double transgenic mice after six-month intervention with curcumin, in order to discuss the neuroprotective effect of curcumin.

METHODAPPswe/PS1dE9dtg mice were randomly divided into the model group, the Rosiglitazone group (10 mg x kg(-1) x d(-1)) and curcumin high (400 mg x kg9-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dosage groups, with C57/BL6J mice of the same age and the same background in the normal control group. After 6 months, the immunohistochemical staining (IHC) and the Western blot method were used to observe the changes in positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area, their distribution and protein expressions.

RESULTBoth of the immunohistochemical staining and the Western blot method showed more positive cell of Aβ40, Aβ42 and ADDLs in hippocampal CA1 area and higher protein expressions in the model group than the normal group (P < 0.01). IHC showed a lower result in the Rosiglitazone group than the model group (P < 0.05), while Western blot showed a much lower result (P < 0.01). The number of Aβ40, Aβ42 and ADDLs positive cells and the protein expressions decreased in the curcumin high group, the medium group showed a significant decrease (P < 0.01), and the low dose group also showed reductions in the protein expressions of Aβ40 and Aβ42.

CONCLUSIONThe six-month intervention with curcumin can significantly reduce the expressions of hippocampal Aβ40, Aβ42 and ADDLs in brains of APPswe/PS1dE9 double transgenic mice. Whether curcumin can impact Aβ cascade reaction by down-regulating expressions of Aβ40, Aβ42 and ADDLs and show the neuroprotective effect needs further studies.

Alzheimer Disease ; drug therapy ; genetics ; metabolism ; Amyloid beta-Peptides ; genetics ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Curcumin ; administration & dosage ; Disease Models, Animal ; Hippocampus ; drug effects ; metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neuroprotective Agents ; administration & dosage ; Plant Extracts ; administration & dosage