Traditional Chinese Medicine and Its Effective Components in Treating Alzheimer's Disease： A Review / 中国实验方剂学杂志

Alzheimer's disease is a common central neurodegenerative disease， mainly manifested by cognitive impairment and non-cognitive neuropsychiatric symptoms that severely affect patients' daily life and behavioral functioning. The pathogenesis of Alzheimer's disease is still unclear， and the western medicine currently used to treat Alzheimer's disease is only symptomatic， with a single pathway， limited efficacy， and many side effects. In recent years， with the deepening of research on Alzheimer's disease， the study and application of traditional Chinese medicine （TCM） in the treatment of Alzheimer's disease have gradually increased. Several studies have shown that TCM and its effective components can exert anti-Alzheimer's disease effects by regulating molecular mechanisms such as pathological protein production and aggregation， oxidative stress， neuroinflammation， ferroptosis， mitochondrial dysfunction， neurogenesis and neurotransmission， and brain-gut axis. This paper summarized the research progress of TCM in the treatment of Alzheimer's disease in recent years， so as to provide a reference for further study of the specific mechanism of TCM in the prevention and treatment of Alzheimer's disease and the discovery of effective components of TCM.

Predictive Value of Serum Albumin Levels for Coronary Artery Calcification in Patients with Early Chronic Kidney Disease / 中山大学学报(医学科学版)

ObjectiveTo explore the correlation between serum albumin levels and coronary artery calcification （CAC） in patients with early-stage chronic kidney disease （CKD）， as well as the value of serum albumin levels in predicting the incidence and severity of CAC. MethodsThe study included 391 early-stage CKD patients who underwent coronary computed tomography angiography （CTA） at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2019 and December 2022. Demographic and biochemistry data， as well as the coronary CTA results， were collected. Based on the coronary artery calcification score （CACS）， all patients were divided into non-CAC group （CACS=0， n=184） and CAC group （CACS>0， n=207）. All patients were further divided into 3 groups based on the serum albumin levels： group A （serum albumin levels<35 g/L， n=30）， group B （35 g/L≤ serum albumin levels< 40 g/L， n=198） and group C （serum albumin levels≥ 40 g/L， n=163）. Univariate and multivariate binary logistic regression analyses were conducted to investigate the association between serum albumin levels and CAC in early-stage CKD patients. Differences in CAC among groups were analyzed by using post-hoc multiple comparisons and ordinal logistic regression model analysis. ResultsPatients with CAC had significantly lower serum albumin levels than those without CAC （P<0.05）. There was a negative correlation between serum albumin levels and CACS in early-stage CKD patients （P<0.01）， as serum albumin decreased in levels， CAC increased in severity. ConclusionsOur study shows that early-stage CKD patients with lower serum albumin levels have a higher incidence of CAC. Low serum albumin level is an independent risk factor for CAC progression.

Research progress on roles and mechanisms of DNA hydroxymethylation in health effects induced by arsenic exposure / 环境与职业医学

Arsenic, a naturally occurring metal-like chemical element, is one of the 10 chemicals of major public concerns listed by the World Health Organization as harmful to the environment and human health. It can enter the human body through breathing, intaking food, drinking water, skin exposure, and other ways, and long-term exposure to arsenic can cause cancer of multiple organs and impaired function of multiple systems. Epigenetic mechanisms play an important role in arsenic-induced health effects, and research suggested that the carcinogenicity of arsenic may be associated with epigenetic changes. Previous studies focused on the effects of arsenic on DNA methylation modification. In recent years, research showed that 5-hydroxymethylcytosine (5-hmC), an intermediate of active demethylation of DNA, can act as a sensitive epigenetic mark and play a crucial role as a "bridge" between arsenic exposure and health effects. Based on the latest research progress on the role of DNA hydroxymethylation in the health effects associated with arsenic exposure, this article briefly described the relationship between the health effects of arsenic exposure and DNA hydroxymethylation, summarized the possible mechanisms of DNA hydroxymethylation in the health effects associated with arsenic exposure, and provided a scientific basis for preventing and treating the health effects associated with arsenic exposure.

Clinical application value of a predictive model for the efficacy of third-generation cephalosporin in treatment of community-acquired spontaneous bacterial peritonitis / 临床肝胆病杂志

ObjectiveTo investigate the clinical application value of a predictive model for the efficacy of third-generation cephalosporin in the treatment of community-acquired spontaneous bacterial peritonitis （CASBP）. MethodsThis prospective study was conducted among 50 patients with liver cirrhosis and CASBP who were admitted to The Ninth Hospital of Nanchang from January 2021 to June 2022， and the patients were randomly divided into optimized treatment group and traditional treatment group， with 25 patients in each group. The patients in the optimized treatment group received ceftazidime or imipenem for initial treatment based on the above predictive model， and those in the traditional treatment group received ceftazidime for initial treatment， with the subsequent use of antibiotics adjusted based on the efficacy of initial treatment. The two groups were compared in terms of the response rate of initial treatment， cure rate on day 5， and 30-day mortality rate. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsAll patients completed the study. The optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.0% vs 60.0%， χ2=5.094， P=0.024）， while there was no significant difference in the cure rate on day 5 between the two groups （80.0% vs 56.6%， χ2=3.309， P=0.069）. As for the patients who received ceftazidime for initial treatment， the optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.9% vs 60.0%， χ2=4.341， P=0.037）， while there was no significant difference in the cure rate on day 5 between the two groups （83.3% vs 56.0%， χ2=2.425， P=0.119）. There was no significant difference in 30-day mortality rate between the two groups （8.0% vs 20.0%， χ2=0.664， P=0.415）. For all patients， there was a significant association between response of initial treatment and cure on day 5 （odds ratio ［OR］=9.643， 95% confidence interval ［CI］： 2.292‍ — ‍40.564） and between cure on day 5 and 30-day mortality （OR=0.138， 95%CI： 0.023‍ — ‍0.813）. ConclusionThis predictive model for efficacy helps clinicians to identify the patients who can benefit from third-generation cephalosporin treatment and improve the efficacy of third-generation cephalosporin in the initial empirical treatment of CASBP.

Risk Factors for in-Hospital Mortality in Patients with Takotsubo Syndrome / 中山大学学报(医学科学版)

ObjectiveTo analyze the risk factors for in-hospital mortality in patients with Takotsubo Syndrome （TTS）. MethodsHospitalization data of consecutive patients with TTS from February 2009 to January 2022 were retrospectively collected and analyzed. Patients were divided into survival group and death group according to outcomes. The basic clinical information， triggering factors， laboratory examinations， electrocardiogram， echocardiography， complications and treatments of the two groups were compared. Univariable logistic regression analysis was used to screen the possible risk factors for in-hospital mortality in TTS patients， and multivariable logistic regression analysis was used to determine the independent risk factors for in-hospital mortality in TTS patients. ResultsA total of 62 TTS patients were included in our study， including 21 males （33.9%）， 41 females （66.1%） and 26 postmenopausal women （41.9%）， with the mean age of （55.6±16.2） years， and physical triggers were found in 50 patients （80.6%）. 17 patients （27.4%） died while 45 patients （72.6%） survived during hospitalization. The death group had lower systolic blood pressure and left ventricular ejection fraction （LVEF）， higher incidence rate of syncope， higher level of N-terminal pro-B natriuretic peptide （NT-proBNP） and hypersensitive troponin T （hs TnT） when compared with survival group （all P value <0.05）. As for the triggering factors， the proportion of TTS induced by neurologic disorders in the death group was higher than that in the survival group （P<0.05）. The death group had higher rates of cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， and respiratory failure （all P value <0.05）. Compared with the survival group， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were higher in the death group （all P value <0.05）. Univariable logistic regression analysis suggested that syncope， NT-proBNP， LVEF， neurologic disorders， cardiogenic shock， malignant ventricular arrhythmia， atrial fibrillation， respiratory failure， therapeutic dopamine， therapeutic norepinephrine， hemodialysis and mechanical ventilation were potential risk factors for in-hospital mortality in TTS patients （all P value <0.05）. Multivariable logistic regression analysis indicated that neurologic disorders ［OR（95%CI）=5.651（1.195，26.715），P=0.029］， atrial fibrillation ［OR（95%CI）=6.217（1.276，30.298）， P=0.024）］ and therapeutic norepinephrin ［OR（95%CI）=8.847（1.912，40.949）， P=0.005］ were independent risk factors for in-hospital mortality in TTS patients. ConclusionsNeurologic disorders， atrial fibrillation and therapeutic norepinephrin are independent risk factors for in-hospital mortality in patients with Takotsubo Syndrome. Clinically， attention should be paid to the prevention and treatment of neurologic disorders and atrial fibrillation； norepinephrine should be carefully used in patients with diagnosed TTS complicated with hemodynamic instability.

Epidemiological characteristics of varicella public health emergency events in Xinwu District Wuxi City in 2016-2020 / 公共卫生与预防医学

Objective To investigate the epidemiological characteristics of varicella public health emergency events (PHEEs) in Xinwu District from 2016 to 2020, and to provide a scientific basis for formulating prevention and control measures. Methods Data was retrieved from “Public Health Emergency Management Information System” in "Chinese Disease Control Information System" and “Jiangsu Provincial Vaccine Management Information System”. Descriptive epidemiological methods were employed to analyze the data. SPSS software was used for statistical analysis. Results A total of 35 varicella PHEEs were reported in Xinwu District from 2016 to 2020, accounting for 57.38% of all PHEEs of infectious diseases in the same period. A total of 1 033 cases were reported, with an attack rate of 1.91%. The events showed a bimodal distribution. A small peak occurred from April to June, and the number of events accounted for 17.14%. A large peak occurred from November to January of the following year, and the number of events accounted for 82.86%. All events occurred in schools. Kindergartens were the most dangerous places, and the number of events accounted for 45.71%. Preschoolers aged 3-6 years accounted for 48.83% of the total cases, and the male-to-female ratio of students was 1.40:1. Among 234 cases with a history of immunization with Varicella Attenuated Live Vaccine (VarV), the longer the time interval from the date of VarV inoculation to the data of onset, the higher the proportion of varicella cases. Varicella PHEEs reporting time was positively correlated with duration (rs=0.391 , P<0.05). Conclusion Early detection, early reporting and early isolation can effectively control the duration of the event. School varicella surveillance should be strengthened during the epidemic peak period. Preschoolers are vulnerable groups. It is suggested that VarV should be included in the inspection work for enrollment in kindergartens.

Circular RNA hsa_circ_0087893 participates in intraventricular hemorrhage occurrence and progression possibly as a competitive endogenous RNA in preterm infants / 南方医科大学学报

OBJECTIVE@#To screen for differentially expressed circular RNAs (circRNAs) in the serum of preterm infants with intraventricular hemorrhage (IVH) and explore the competitive endogenous RNA (ceRNA) mechanism of circRNAs in IVH in these infants.@*METHODS@#Fifty preterm infants (gestational age of 28 to 34 weeks) admitted in our department between January, 2019 and January, 2020 were enrolled in this study, including 25 with a MRI diagnosis of IVH and 25 without IVH. Serum samples were collected from 3 randomly selected infants from each group for profiling differentially expressed circRNAs using circRNA array technique. Gene ontology (GO) and pathway analyses were performed to reveal the function of the identified circRNAs. The circRNA-miRNA-mRNA network was constructed to identify the co-expression network of hsa_circ_ 0087893.@*RESULTS@#A total of 121 differentially expressed circRNAs were identified in the infants with IVH, including 62 up-regulated and 59 down-regulated circRNAs. GO and pathway analyses showed that these circRNAs were involved in multiple biological processes and pathways, including cell proliferation, activation and death, DNA damage and repair, retinol metabolism, sphingolipid metabolism, cell adhesion molecules. Among these circRNAs, hsa_circ_0087893 was found to have significant down-regulation in IVH group and co-express with 41 miRNAs and 15 mRNAs (such as miR-214-3p, miR-761, miR-183-5p, AKR1B1, KRT34, PPP2CB, and HPRT1).@*CONCLUSION@#The circRNA hsa_circ_0087893 may function as a ceRNA and play an important role in the occurrence and progression of IVH in preterm infants.

A Novel Chinese Medicine Formula Inhibits Non-small Cell Lung Cancer by Triggering Oxidative Stress Dependent on Pentose Phosphate Pathway / 中国肺癌杂志

BACKGROUND@#Non-small cell lung cancer (NSCLC) is one of the most lethal malignancies worldwide. A novel Chinese medicine formula-01 (NCHF-01) has shown significant clinical efficacy in the treatment of NSCLC, but the mechanism of this formula in the treatment of NSCLC is not fully understood. The aim of this study is to investigate the molecular mechanism of NCHF-01 in inhibiting NSCLC.@*METHODS@#Lewis lung cells (LLC) tumor bearing mice were established to detect the tumor inhibitory effect of NCHF-01. The morphological changes of tissues and organs in LLC tumor-bearing mice were detected by hematoxylin-eosin (HE) staining. NSCLC cells were treated by NCHF-01. The effects of cell viability and proliferation were detected by MTT and crystal violet staining experiment. Flow cytometry was used to detect cell cycle, apoptosis and reactive oxygen species (ROS). Network pharmacology was used to predict the mechanism of its inhibitory effect of NSCLC. Western blot and immunohistochemistry (IHC) were used to detect the expression of related proteins.@*RESULTS@#NCHF-01 can inhibit tumor growth in LLC tumor-bearing mice, and has no obvious side effects on other tissues and organs. NCHF-01 could inhibit cell viability and proliferation, induce G2/M phase arrest and apoptosis, and promote the increase of ROS level. Network pharmacological analysis showed that NCHF-01 exerts anti-NSCLC effects through various biological processes such as oxidative stress and central carbon metabolism. NCHF-01 can reduce the protein expression and enzyme activity of the key enzymes 6-phosphate glucose dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) in the pentose phosphate pathway (PPP).@*CONCLUSIONS@#NCHF-01 can inhibit NSCLC through oxidative stress dependent on the PPP.

The relationship between the characteristics of tears and the progression of Stanford type B aortic dissection after endovascular treatment / 中华外科杂志

Endovascular treatment of Stanford type B aortic dissection (type B dissection) has been widely used. There will be complications such as aortic dilatation, which will lead to poor prognosis of some patients. With more in-depth researches, it was found that there was a possible correlation between the prognosis of type B dissection and tears, such as the increasing of aortic diameter would be faster with longer tears, and the location of the tear will affect the thrombosis of the false lumen. Studies on hemodynamics have also found that different characteristics of tears of aortic dissection can cause changes in the pressure, blood flow rate and blood capacity in the true and false lumens recently. The hemodynamic changes can be used to predict the prognosis of type B dissection. The main characteristics of tears included the size, position, number of tears, residual tears and stent graft induced new entry. Describing the effect of tear characteristics on the development of type B dissection, can provide the basis for the clinical treatment and further research of type B dissection.

Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations / 中华病理学杂志

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

Effects and mechanisms of total flavones of Abelmoschus manihot in inhibiting podocyte necroptosis and renal fibrosis in diabetic kidney disease / 中国中药杂志

Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.

Maxent modeling for predicting the global potential distribution of talaromycosis marneffei / 中国热带医学

@#Abstract: Objective　To predict the potential distribution of talaromycosis marneffei (TSM) and analyze its driving factors, so as to provide evidence for the surveillance and prevention of this disease. Methods　The data of all laboratory-confirmed, non-duplicating TSM published in the English and Chinese literature from the first case in January 1964 to December 2018 was collected. A Maxent ecology model using environmental variables, Rhizomys distribution and HIV/AIDS epidemic was developed to forecast ecological niche of TSM worldwide, as well as identify the driving factors. Results　A total of 705 articles (477 in Chinese and 228 in English) were obtained during the study period. After excluding imported cases, a total of 100 foci information were included in the model. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was 0.997 for the training set and 0.991 for the test set. Maxent model revealed that Rhizomys distribution, mean temperature of warmest quarter, precipitation of wettest month, HIV/AIDS epidemic and mean temperature of driest quarter were the top 5 important variables affecting TSM distribution. In addition to identifying traditional TSM endemic areas (South of the Yangtze River in China, Southeast Asian, North and Northeast India), other potential endemic areas were also identified, including parts of the North of the Yangtze River, Central America, West Coast of Africa, East Coast of South America, the Korean Peninsula and Japan. Conclusion　Our finding has discovered hidden high-risk areas and provided insights about driving factors of TSM distribution, which will help inform surveillance strategies and improve the effectiveness of public health interventions against TM infections.

The In Vivo Intervention and Relative Mechanism of Genistein on the Inflammation and Thrombophilia in Lymphoma-Bearing Mice / 中国实验血液学杂志

OBJECTIVE@#To investigate the in vivo intervention and relative mechanism of Genistein (GEN) on tumor-associated inflammatory and tumor thrombophilia in lymphoma-bearing mice.@*METHODS@#Forty female Balb/c mice aged 5-6 weeks were injected with murine-derived Pro B-cell lymphoma cell line 38B9 to establish a lymphoma mouse model, which was randomly divided into control group, tumor-bearing group, GEN drug intervention group and cyclophosphamide (CTX）drug intervention group. Histopathologic was used to evaluate the tumorigenesis. Tumor formation was observed, and tumor tissues were collected of HE and immunohistochemical staining. ELISA and flow cytometry were used to detect the expression of inflammatory factors and the changes of thrombus indices in plasma after intervention of GEN and Cyclophosphamide (CTX) respectively. Immunohistochemistry method was used to detect the expression of CD19 in tomor tissues of tummor bearing mice.@*RESULTS@#After 14 days of tumor bearing, the mice were tumorigenic. The lymphoma cells were diffusely distributed in the tumor tissue and the expression of CD19 in the tumor tissue was positive. The inflammatory factors such as IL-6, NETs and CLEC-2, and thrombotic indices such as TF, FIB and D-D in lymphoma-bearing mice were significantly higher than those before tumor-injection and lower than those after drug-intervention (all P<0.05). The levels of CLEC-2 and D-D in GEN group were significantly lower than those in CTX group (P<0.05).@*CONCLUSION@#Tumor-associated inflammation and thrombophilia exist in lymphoma-bearing mice. GEN shows better anti-inflammatory and anti-thrombotic effects compared with CTX by interfering with tumor inflammatory factors.

Progress on diagnosis and treatment of latent tuberculosis infection / 浙江大学学报·医学版

One fourth of the global population has been infected with Mycobacterium tuberculosis, and about 5%-10% of the infected individuals with latent tuberculosis infection (LTBI) will convert to active tuberculosis (ATB). Correct diagnosis and treatment of LTBI are important in ending the tuberculosis epidemic. Current methods for diagnosing LTBI, such as tuberculin skin test (TST) and interferon-γ release assay (IGRA), have limitations. Some novel biomarkers, such as transcriptome derived host genes in peripheral blood cells, will help to distinguish LTBI from ATB. More emphasis should be placed on surveillance in high-risk groups, including patients with HIV infection, those using biological agents, organ transplant recipients and those in close contact with ATB patients. For those with LTBI, treatment should be based on the risk of progression to ATB and the potential benefit. Prophylactic LTBI regimens include isoniazid monotherapy for 6 or 9 months, rifampicin monotherapy for 4 months, weekly rifapentine plus isoniazid for 3 months (3HP regimen) and daily rifampicin plus isoniazid for 3 months (3HR regimen). The success of the one month rifapentine plus isoniazid daily regimen (1HP regimen) suggests the feasibility of an ultra-short treatment strategy although its efficacy needs further assessment. Prophylactic treatment of LTBI in close contact with MDR-TB patients is another challenge, and the regimens include new anti-tuberculosis drugs such as bedaquiline, delamanid, fluoroquinolone and their combinations, which should be carefully evaluated. This article summarizes the current status of diagnosis and treatment of LTBI and its future development direction.

Effect and mechanism of Dahuang Zhechong Pills in improving liver aging in rats by regulating ROS-mediated PI3K/Akt/FoxO4 signaling pathway / 中国中药杂志

Recent studies have shown that the occurrence and development of common liver diseases, including non-alcoholic fatty liver disease, cirrhosis, and liver cancer, are related to liver aging(LA). Therefore, to explore the effect and mechanism of Dahuang Zhechong Pills(DHZCP), a traditional classic prescription in improving LA with multiple targets, the present study randomly divided 24 rats into a normal group, a model group, a DHZCP group, and a vitamin E(VE) group, with six rats in each group. The LA model was induced by continuous intraperitoneal injection of D-galactose(D-gal) in rats. For the LA model rats, the general situation was evaluated by aging phenotype and body weight(BW). LA was assessed by the pathological characteristics of hepatocyte senescence, hepatic function indexes, the staining characteristics of phosphorylated histone family 2A variant(γ-H2AX), and the expression levels of cell cycle arrest proteins(P21, P53, P16) and senescence-associated secretory phenotype(SASP) in the liver. The activation of the reactive oxygen species(ROS)-mediated phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/forkhead box protein O4(FoxO4) signaling pathway was estimated by hepatic ROS expression feature and the protein expression levels of the key signaling molecules in the PI3K/Akt/FoxO4 signaling pathway. The results showed that after the treatment with DHZCP or VE for 12 weeks, for the DHZCP and VE groups, the characterized aging phenotype, BW, pathological characteristics of hepatocyte senescence, hepatic function indexes, relative expression of ROS in the liver, protein expression levels of key signaling molecules including p-PI3K, p-Akt, and FoxO4 in the liver, staining characteristics of γ-H2AX, and the protein expression levels of P16, P21, P53, interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in the liver were improved, and the effects of DHZCP and VE were similar. Based on the D-gal-induced LA model in rats, this study demonstrates that DHZCP can ameliorate LA with multiple targets in vivo, and its effects and mechanism are related to regulating the activation of the ROS-mediated PI3K/Akt/FoxO4 signaling pathway in the liver. These findings are expected to provide new pharmacological evidence for the treatment of DHZCP in aging-related liver diseases.

Effects and mechanisms of total flavones of Abelmoschus manihot in attenuating diabetic tubulopathy by targeting endoplasmic reticulum stress-induced cell apoptosis / 中国中药杂志

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.

Effects and mechanisms of total flavones of Abelmoschus manihot in improving insulin resistance and podocyte epithelial-mesenchymal transition in diabetic kidney disease based on IRS1/PI3K/Akt pathway / 中国中药杂志

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.

Comparison of HPLC fingerprints and determination of main components of Viticis Fructus from different species / 中国中药杂志

In order to comprehensively evaluate the quality of Viticis Fructus, this study established HPLC fingerprints and evaluated the quality of 24 batches of Viticis Fructus samples from different species by similarity evaluation and multivariate statistical analysis(PCA, HCA, PLS-DA). On this basis, an HPLC method was established to compare the content differences of the main components, including casticin, agnuside, homoorientin, and p-hydroxybenzoic acid. The analysis was performed on the chromatographic column(Waters Symmetry C_(18)) with a gradient mobile phase of acetonitrile(A)-0.05% phosphoric acid solution(B) at the flow rate of 1 mL·min~(-1) and detection wavelength of 258 nm. The column temperature was 30 ℃ and the injection volume was 10 μL. The HPLC fingerprint of 24 batches of Viticis Fructus samples was established with 21 common peaks, and nine peaks were identified. Similarity analysis was carried out based on chromatographic data of 24 batches of chromatographic data of Viticis Fructus, and the results showed that except for DYMJ-16, the similarity of Vitex trifolia var. simplicifolia was ≥0.900, while that of V. trifolia was ≤0.864. In addition, the similarity analysis of two different species showed that the similarity of 16 batches of V. trifolia var. simplicifolia was 0.894-0.997 and that of the eight batches of V. trifolia was between 0.990 and 0.997. The results showed that the similarity of fingerprints of these two species was different, but the similarity between the same species was good. The results of the three multivariate statistical analyses were consistent, which could distinguish the two different species. The VIP analysis results of PLS-DA showed that casticin and agnuside contributed the most to the distinction. The content determination results showed that there was no significant difference in the content of homoorientin and p-hydroxybenzoic acid in Viticis Fructus from different species, but the content of casticin and agnuside was significantly different in different species(P<0.01). The content of casticin was higher in V. trifolia var. simplicifolia, while agnuside was higher in V. trifolia. The findings of this study show that there are differences in fingerprint similarity and component content of Viticis Fructus from different species, which can provide references for the in-depth study of the quality and clinical application of Viticis Fructus.

Clinical characteristics of Danon disease / 中华心血管病杂志

Objective: To review the clinical data of 7 patients with Danon disease and analyze their clinical characteristics. Methods: The medical records of 7 patients with Danon disease, who were hospitalized in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences from April 2008 to July 2021, were reviewed and summarized, of which 6 cases were diagnosed as Danon disease by lysosomal-associated membrane protein-2 (LAMP-2) gene mutation detection and 1 case was diagnosed by clinicopathological features. Clinical manifestations, biochemical indexes, electrocardiogram, echocardiography, skeletal muscle and myocardial biopsy and gene detection results were analyzed, and patients received clinical follow-up after discharge. Results: Six patients were male and average age was (15.4±3.5) years and the average follow-up time was (27.7±17.0) months. The main clinical manifestations were myocardial hypertrophy (6/7), decreased myodynamia (2/7) and poor academic performance (3/7). Electrocardiogram features included pre-excitation syndrome (6/7) and left ventricular hypertrophy (7/7). Echocardiography examination evidenced myocardial hypertrophy (6/7), and left ventricular dilatation and systolic dysfunction during the disease course (1/7). The results of skeletal muscle biopsy in 6 patients were consistent with autophagy vacuolar myopathy. Subendocardial myocardial biopsy was performed in 3 patients, and a large amount of glycogen deposition with autophagosome formation was found in cardiomyocytes. LAMP-2 gene was detected in 6 patients, and missense mutations were found in all these patients. During the follow-up period, implantable cardioverter defibrillator implantation was performed in 1 patient because of high atrioventricular block 4 years after diagnosis, and there was no death or hospitalization for cardiovascular events in the other patients. Conclusion: The main clinical manifestations of Danon disease are cardiomyopathy, myopathy and mental retardation. Pre-excitation syndrome is a common electrocardiographic manifestation. Autophagy vacuoles can be seen in skeletal muscle and myocardial pathological biopsies. LAMP-2 gene mutation analysis is helpful in the diagnose of this disease.

Autophagy-regulated strategies in pre-clinical studies of inflammatory bowel disease / 药学学报

Inflammatory bowel disease (IBD) is a group of chronic idiopathic colorectal inflammatory diseases with a progressive and unpredictable course, including ulcerative colitis (UC) and Crohn's disease (CD). Abnormal intestinal inflammation and immune response contribute to the pathogenesis of IBD. Autophagy as an essential catabolic process in cells, has been demonstrated to have associations with a variety of inflammatory diseases including IBD. Here, we review the relationship between autophagy dysfunction and the process of IBD. The progress of several autophagy regulators for intestinal epithelial cells and macrophages is highlighted (inflammasome inhibitors, intestinal flora regulators, and other signal regulators) in the current studies on IBD.