ObjectiveTo explore the evolution principles of symptoms including deficiency， phlegm and blood stasis， and of the functional near-infrared spectroscopy （fNIRS） cerebral hemodynamic characteristics at various stages in patients of Alzheimer's disease. MethodsA total of 497 patients with complaint of memory loss were included， and were divided into subjective cognitive decline （SCD） group （198 participants）， mild cognitive impairment （MCI） group （228 participants） and dementia （AD） group （71 participants）. Neuropsychological evaluation， traditional Chinese medicine （TCM） syndrome investigation， and fNIRS data collection of prefrontal cortex were performed in each group. Descriptive statistics were used to analyze the distribution of TCM syndromes and the difference of TCM syndrome scores in each group； logistic regression was used to analyze the influence of TCM syndromes on the incidence of the patients； association rules were used to analyze the TCM syndromes of the patients； the hemodynamic characteristics of fNIRS in the prefrontal cortex of each group were compared. ResultsKidney essence deficiency syndrome was the dominant syndrome in all stages of AD. There were statistically significant differences in the distribution frequency of kidney essence deficiency， phlegm turbidity obstructing orifices， blood stasis obstructing collaterals， qi and blood deficiency， heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes among the three groups （P＜0.01）， and the scores of kidney essence deficiency syndrome among the three groups were statistically significant （P＜0.01）. Logistic regression analysis showed that kidney essence deficiency， and qi and blood deficiency syndromes were the main risk factors for the SCD group （P＜0.05）， phlegm turbidity obstructing orifices syndrome was the main risk factor for the MCI group （P＜0.05）， and heat toxin in the interior， and fu-organ stagnation and turbidity retention syndromes were the main risk factors for the AD group （P＜0.05）. The association rule analysis showed that the combination of kidney essence deficiency plus phlegm turbidity obstructing orifices had the highest support （33.33%） in the SCD group， and the combination of kidney essence deficiency plus blood stasis obstructing collaterals had the highest support （32.90% and 52.13%） in both the MCI and AD group. The prefrontal fNIRS results showed that the mean ∆HbO₂ concentration in the left dorsolateral prefrontal cortex （LDLPFC） decreased sequentially among the three groups （P＜0.05）， and the mean ∆HbO₂ concentration in the LDLPFC was negatively correlated with the MoCA score among the three groups （r = -0.142， P＜0.05）. Further analysis showed that the mean ∆HbO₂ concentration in the LDLPFC of patients with kidney essence deficiency syndrome were statistically significant differences among the three groups （P＜0.05）. ConclusionKidney deficiency is the basis of the pathogenesis of AD， and the key brain area damaged is the LDLPFC. Turbid pathogens such as phlegm and blood stasis are the pathological factors that aggravate the disease， and the syndromes of AD show the evolution law of deficiency and excess as “kidney deficiency→phlegm turbidity→blood stasis→turbid toxin”. The changes in prefrontal hemodynamics based on fNIRS are consistent with the changes in the characteristics of symptoms， which can be used to assess the degree of cognitive impairment in AD patients.

Integrase inhibitors (INSTIs) are the newest class of antiretroviral drug which are available to people living with the human immunodeficiency virus (HIV). Since 2007, five types of INSTIs have been marketed: Raltegravir, Elvitegravir, Dolutegravir, Bictegravir and Cabotegravir, all of which were approved by the US Food and Drug Administration (FDA) for use in the initiation of antiretroviral therapy (ART) in treatment-na?ve individuals. Compared with other types of antiretroviral drugs, INSTIs have better efficacy and tolerability, so many countries around the world have listed INSTIs-containing regimens as the preferred regimen for HIV ART. In recent years, with the widespread use of INSTIs, some research data suggest that INSTIs may have some adverse effects (AEs), such as central nervous system symptoms, abnormal lipid metabolism, weight gain, abnormal liver and kidney function, etc. This review summarizes the current use of INSTIs in people living with the HIV, and highlights the clinical efficacy and their AEs among the five types of INSTIs in China.

The specific binding of T cell receptors (TCRs) to antigenic peptides plays a key role in the regulation and mediation of the immune process and provides an essential basis for the development of tumour vaccines. In recent years, studies have mainly focused on TCR prediction of major histocompatibility complex (MHC) class I antigens, but TCR prediction of MHC class II antigens has not been sufficiently investigated and there is still much room for improvement. In this study, the combination of MHC class II antigen peptide and TCR prediction was investigated using the ProtT5 grand model to explore its feature extraction capability. In addition, the model was fine-tuned to retain the underlying features of the model, and a feed-forward neural network structure was constructed for fusion to achieve the prediction model. The experimental results showed that the method proposed in this study performed better than the traditional methods, with a prediction accuracy of 0.96 and an AUC of 0.93, which verifies the effectiveness of the model proposed in this paper.
Receptors, Antigen, T-Cell/immunology* ; Histocompatibility Antigens Class II/metabolism* ; Humans ; Neural Networks, Computer ; Peptides/metabolism* ; Protein Binding

Objective:Healthy life expectancy (HLE), which combines life expectancy with health, is an essential comprehensive measure of life length and quality. This article aimed to systematically review the methods for defining and measuring HLE and describe application studies published, providing a reference for decision makers to select and develop methods suitable for China's conditions to measure HLE.Methods:Seven Chinese and English literature databases were searched up to May 7, 2022, and several related reviews and bibliography were manually retrieved. Systematic reviews and empirical research were included concerning HLE indicators and measurement of HLE. Information including the study area, type of the study, study population, HLE index, measurement method, data sources, and results from application studies published in the last five years were extracted. The evolution of the definition of HLE, the scope of different indicators, the measurement scale of health, and measurement methods, were all collected. Results of the empirical research related to measurement methods of indicators were summarized. The study followed the scoping review framework and was written according to the PRISMA-ScR statement.Results:A total of 84 articles were included, including 13 reviews, 17 original studies related to HLE index definition, ten original studies related to index measurement, and 44 empirical studies conducted in the past five years. There were as many as 20 indicators related to HLE, and each scale had its emphasis. A total of ten methods measuring HLE were identified, which vary in the definition of health, whether using weight, and the data type. The most commonly used indicators in the past five years were disability-free life expectancy and HLE. For the method of HLE calculation, Sullivan's method was mainly used for cross-sectional data, and the multistate life table was mainly used for longitudinal data.Conclusions:There are various definitions and measurement methods of HLE, but none are suitable for all scenarios. To summarize the HLE concept, health evaluation techniques, measurement methods, and application studies published worldwide can provide a reference for the localization of HLE measurement in China.

Objective:To evaluate the incidence intensity of hand, foot, and mouth disease (HFMD) in 2018/2019 season in southern China by Moving Epidemic Method (MEM), and compare the intensity among provinces, so as to provide basis for optimizing the allocation of public health resources.Methods:The weekly incidence data of HFMD of children under 5 years old in 15 provinces of southern China from March 1, 2012 to February 28, 2019 were collected from Disease Surveillance Reporting System of Chinese Center for Disease Control and Prevention, and the epidemic intensity threshold of each province in southern China during this period was calculated and evaluated by MEM.Results:In the first incidence peak of 2018/2019 HFMD season, in 15 provinces in the south China, 6 provinces (Jiangsu, Zhejiang, Jiangxi, Chongqing, Sichuan and Yunnan) reported very high incidence rates in children under 5 years old while Guangdong, Guangxi and Hainan provinces had low incidence level. In the second incidence peak, the incidences in 6 provinces (Shanghai, Jiangsu, Zhejiang, Chongqing, Sichuan and Yunnan) reached very high levels. The incidences in remaining provinces also reached medium or high levels. In most provinces, the thresholds in the first incidence peak were higher than those in the second incidence peak, but Chongqing and Sichuan were different. The results of model validation showed that the sensitivity and specificity of MEM were higher than 70% except for Hainan, Chongqing and Yunnan.Conclusions:For southern provinces with two incidence peaks in HFMD season, MEM can be used to determine the epidemic intensity thresholds of different incidence peaks by dividing the disease season to analyze the incidence intensity of HFMD in different stages. The epidemic intensity threshold established by MEM integrates the historical data, and the province (city) with extremely high epidemic level identified represents that the province (city) has an abnormal increase compared with the historical incidence level, which requires more attention from all areas and timely implementation of prevention and control measures.

Objective:To characterize the epidemiology of severe hand, foot and mouth disease (HFMD) in China from 2008 to 2018 and provide evidence for the prevention and control of severe HFMD.Methods:The incidence data of severe HFMD cases from 2008 to 2018 were collected from the National Notifiable Infectious Diseases Reporting System of Chinese Center for Disease Control and Prevention. Descriptive epidemiological methods were used to analyze distributions, pathogen constituent and change of severe HFMD. Joinpoint regression model was used to analyze the trends of severity rate, proportion of severe cases and severe fatality rate.Results:From 2008 to 2018, a total of 157 065 cases of severe HFMD were reported in China, with an average annual case-severity rate of 1.05/100 000, a severe case proportion of 0.76 % and a severity-fatality rate of 2.34 %. The severity rate and the proportion of severe cases showed a downward trend after 2010, and severe fatality rate decreased significantly after 2014. The severe cases mainly occurred in infants aged ≤3 years (91.47 %), more boys were affected than girls (1.78∶1). The median age of severe HFMD cases caused by EV-A71 was highest (1.99 years) and increased year by year, other enterovirus infection cases accounted for a higher proportion in infants aged ≤1 year (66.56 %). The incidence peak occurred during April-July, other enteroviruses replaced EV-A71 as the predominant serotype in 2018 (61.97 %). The incidence of severe HFMD were high in some provinces in southwestern, central and eastern China. Conclusion:The overall severity rate, proportion of severe cases and severe fatality rate of HFMD in the mainland of China have shown a downward trend. The predominant pathogen in some provinces has changed from EV-A71 to other enteroviruses. It is necessary to strengthen the prevention and control of HFMD in key population, high incidence seasons and areas and carry out the surveillance of various pathogens of HFMD.

Objective To analyze the susceptibility of serotonin promoter single nucleotide polymorphism (SNP)rs956304 to chemotherapy-induced nausea and vomiting(CINV)in colorectal cancer.Methods Rs956304 genotypes and the clinical pathological data of 166 patients with colorectal cancer from September 2009 to April 2014 were retrospectively analyzed. Rs956304 genotype was analyzed by sequencing. The correlations between rs956304 genotype,factors of clinical pathology and CINV were analyzed by chi-square test. Unconditional logistic regression model was used to analyze the independent effect of rs956304 genotype on colorectal cancer CINV. Results Chi-square test showed that moderate to severe CINV was associated with rs956304 AG+GG genotype (P=0.011). Unconditional logistic regression model showed that the patients with AG+GG genotype had a signifi-cant higher risk of moderate to severe CINV than AA genotype(OR=3.215,95% CI:1.202 to 8.599,P=0.020). Conclusion Rs956304 AG+GG genotype is an independent risk factor for moderate to severe colorectal cancer CINV.

Objective:To establish T lineage leukemia Jurkat cell mice model of over expression of C-terminal Src kinase binding protein( Cbp ) and Cbp palmitoylation and to research the effect of Cbp and Cbp palmitoylation to proliferation of Jurkat cell.Methods:Virus transfected cell of neg-EGFP,Cbp-EGFP and Cbp-m-EGFP were used in mice model.24 female BALB/c-nu mice were randomly divided into blank control group,empty virus control group,over expression of CBP group and Cbp palmitoylation group, 6 mice in each group.The nude mice were weighed in 0,1,2,3,4,5 weeks.The amount of white blood cell in peripheral blood were counted in 0, 1, 2, 3, 4, 5 weeks.The proliferation of Jurkat cell in peripheral blood of mice were observed by laser confocal microscope.The pathological changes of liver were observed using HE staining.The proliferation of Jurkat cell in the bone marrow and peripheral blood of mice were detected with flow cytometry.Results:The weight of mice in over expression of Cbp group was less than that in blank control group,but higher than that in empty virus control group and Cbp palmitoylation group.The weight of mice in Cbp palmitoylation group was less than that in blank control group,empty virus control group and over expression of Cbp group.The amount of white blood cell in peripheral blood and proliferation of Jurkat cell in liver, bone marrow and peripheral blood of mice in over expression of Cbp group was higher than that in blank control group, but less than that in empty virus control group and Cbp palmitoylation group.The amount of white blood cell in peripheral blood and proliferation of Jurkat cell in liver, bone marrow and peripheral blood of mice in Cbp palmitoylation group was higher than that in blank control group,empty virus control group and over ex-pression of Cbp group.Conclusion:Over expression of Cbp and Cbp palmitoylation in T lineage leukemia Jurkat cell mice model was established.Over expression of Cbp has inhibitory effect on the proliferation of Jurkat cell.Cbp palmitoylation has promotable effect on the proliferation of Jurkat cell.

OBJECTIVETo investigate the endovascular treatments for the ruptured aneurysms located at anterior communicating artery complex (ACoAC).

METHODSThe data of patients with ruptured ACoAC aneurysms treated in Department of Neurosurgery, First Affiliated Hospital to Fourth Military Medical University from May 2013 to December 2014 was retrospectively analyzed. Sixty-six cases were recruited including 50 male and 16 female patients. The patients aged from 31 to 69 years old, averaging (51±8) years. The Hunt-Hess grade at admission were 13 cases with grade Ⅰ, 36 cases with grade Ⅱ, 11 cases with grade Ⅲ, and 6 cases with grade Ⅳ. The most diameter of aneurysms sac: 14 cases less than or equal to 3 mm, 36 cases more than 3 mm but less than or equal to 7 mm, and 16 cases more than 7 mm. The height diameter/neck width ratio: 8 cases with absolute wide neck, 50 cases with relatively wide neck, and 8 cases with narrow neck. There were 28 cases underwent single micro-catheter embolization, 18 cases underwent double micro-catheters embolization, 14 cases underwent stent-assisted embolization and 6 cases underwent balloon-assisted embolization. The patients were followed up for 6 to 12 months and evaluated by modified Rankin score (mRS) and digital subtraction angiography (DSA). The ratio of total embolization, recurrence rate, and time from operation to reexamination of four groups managed by different endovascular treatment were compared by χ(2) test or F test.

RESULTSSixty cases were totally embolized, 3 cases subtotally embolized, 3 cases incompletely embolized. Mild hemiparalysis and aphasia occurred in 2 cases, and 1 case died of infarction induced by subarachnoid haemorrhage. The mRS at six months after operation were 0 in 31 cases, 1 in 22 cases, 2 in 8 cases, 3 in 2 cases, 4 in 2 cases, 6 in 1 case. All the included cases reexamined the DSA at averaging (7.5±1.0) month post-operatively and 4 cases recurred. There were not significant differences of the ratio of total embolization, recurrence rate, time from operation to reexamination among four groups (all P>0.05).

CONCLUSIONThe endovascular treatment maybe an ideal management for ruptured ACoAC aneurysms.

Adult ; Aged ; Aneurysm, Ruptured ; therapy ; Catheters ; Embolization, Therapeutic ; Female ; Humans ; Intracranial Aneurysm ; therapy ; Male ; Middle Aged ; Postoperative Period ; Recurrence ; Retrospective Studies ; Stents ; Treatment Outcome

BACKGROUND:Recently, glucocorticoid-induced necrosis of femoral head has been much studied. However, the precise Wnt signaling pathway by which puerarin suppresses adipogenic differentiation of glucocorticoid-induced bone marrow mesenchymal stem cells adipogenic differentiation of glucocorticoid-induced bone marrow mesenchymal stem cells remains unconfirmed. OBJECTIVE:To investigate the expression of Wnt signaling pathway related genes and the key factor protein,β-catenin, during adipogenic differentiation of glucocorticoid-induced rat bone marrow mesenchymal stem cells treated by puerarin. METHODS:The third generation of bone marrow mesenchymal stem cells were cultured with Dulbecco’s modified Eagle’s medium containing blank serum (blank control group), dexamethasone (hormone group), dexamethasone with puerarin low dose group, the middle dose group and high dose group. After 6 days of culture, in the above five groups, the expressions of Wnt/β-catenin signaling pathway members, Wnt10b mRNA, GSK3βmRNA,β-catenin mRNA, were detected using RT-PCR assay, and the expression ofβ-catenin protein was detected using western blot assay.
RESULTS AND CONCLUSION:Compared with the control group, the Wnt10b mRNA,β-catenin mRNA andβ-catenin protein expressions were significantly higher in puerarin groups, but GSK3βmRNA expression was significantly lower in the puerarin groups. These findings suggest that puerarin effects on inhibition of adipogenic differentiation of glucocorticoid-induced bone marrow mesenchymal stem cells probably are realized through the activation of Wnt/β-catenin signal pathway and regulation of the key factor Wnt10b mRNA, GSK3βmRNA,β-catenin mRNA, andβ-catenin protein expressions. The mechanism by which puerarin prevents glucocorticoid-induced necrosis of femoral head not only improves local microcirculation of the femoral head, but also relates to its inhibitory effects on adipogenic differentiation of glucocorticoid-induced bone marrow mesenchymal stem cells.