The role of glucose metabolism reprogramming and its targeted therapeutic agents in inflammation-related diseases / 药学学报

Cells undergo glucose metabolism reprogramming under the influence of the inflammatory microenvironment, changing their primary mode of energy supply from oxidative phosphorylation to aerobic glycolysis. This process is involved in all stages of inflammation-related diseases development. Glucose metabolism reprogramming not only changes the metabolic pattern of individual cells, but also disrupts the metabolic homeostasis of the body microenvironment, which further promotes aerobic glycolysis and provides favourable conditions for the malignant progression of inflammation-related diseases. The metabolic enzymes, transporter proteins, and metabolites of aerobic glycolysis are all key signalling molecules, and drugs can inhibit aerobic glycolysis by targeting these specific key molecules to exert therapeutic effects. This paper reviews the impact of glucose metabolism reprogramming on the development of inflammation-related diseases such as inflammation-related tumours, rheumatoid arthritis and Alzheimer's disease, and the therapeutic effects of drugs targeting glucose metabolism reprogramming on these diseases.

Development of an in vitro screening method for idiosyncratic hepatotoxic components in traditional Chinese medicine: a case study with Epimedii Folium and Psoraleae Fructus / 药学学报

Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.

Spatial-temporal Distribution and Influencing Factors of Late Diagnosis of HIV/AIDS Based on Bayes Spatial-temporal Model / 中山大学学报(医学科学版)

ObjectivesTo analyze the spatial and temporal clustering characteristics and related influencing factors of late diagnosis of HIV/AIDS in Lanzhou， to identify its high-risk areas and time trends in Lanzhou， and to provide a theoretical basis for developing targeted HIV/AIDS prevention and control strategies in Lanzhou. MethodsThe subjects of this study were adult HIV/AIDS cases reported in Lanzhou City between 2011 and 2018. Data used in the study were sourced from the Lanzhou Center for Disease Control and Prevention and the Lanzhou Statistical Yearbook. To analyze the spatial distribution characteristics and influencing factors of the relative risk （RR） of late HIV/AIDS diagnosis， Bayes spatial-temporal model was used. ResultsA total of 1984 new HIV/AIDS cases were reported in Lanzhou from 2011 to 2018， with an mean age of 37.51 years and predominantly male （91.8%）. The number of late diagnosis cases was 982， with an mean age of 39.67 years and a predominance of males （91.8%）. Late diagnosis was more common in older individuals and women with HIV/AIDS. Chengguan District （51.1%）， Anning District （50.3%） and Yuzhong County （51.9%） had an above-average proportion of late diagnosis of HIV/AIDS. The proportion of late diagnosis cases in Lanzhou showed a fluctuating upward trend from 2011 to 2018. The results of Bayes spatial-temporal model showed that the risk of late HIV/AIDS diagnosis in Lanzhou had fluctuated from 2011 to 2015， and then increased rapidly after 2015 ［RR （95% credibility interval， 95%CI） increased from 1.01 （0.84， 1.23） to 1.11 （0.77， 1.97）］； the trends of risk of late diagnosis in Honggu district and three counties were similar to the overall trend in Lanzhou city， while the risk of late diagnosis in Chengguan District and Qilihe District showed a decreasing trend. The regions with the RR for late diagnosis greater than 1 included Yongdeng County （RR=1.07， 95% CI： 0.55， 1.96）， Xigu District （RR=1.04， 95% CI： 0.67， 1.49）， Chengguan District （RR=2.41， 95% CI： 0.85， 6.16）， and Qilihe District （RR=2.03， 95% CI： 1.10， 3.27）. Besides， the heatmap analysis showed that Chengguan District and Qilihe District were the hot spots. The influencing factors analysis showed that the higher GDP per capita （RR=0.65， 95% CI： 0.35， 0.90） and the larger proportion of males with HIV/AIDS cases （RR=0.53， 95% CI： 0.19， 0.92） could lead to the lower the relative risk of late HIV/AIDS diagnosis. However， the higher the population density （RR=1.35， 95% CI： 1.01， 1.81） caused the higher the risk of late diagnosis. ConclusionOur study shows the risk of late diagnosis of HIV/AIDS in Lanzhou was on the rise， and there are significant regional differences. GDP per capita， the proportion of males in HIV/AIDS cases and population density are influencing factors in the late diagnosis of HIV/AIDS. Therefore， for regions with a high risk of late diagnosis or related risk factors， targeted HIV screening and prevention services should be given priority in order to reduce the proportion and risk of late diagnosis of HIV/AIDS.

Capacity building in schistosomiasis control institutions in China: a cross-sectional study / 中国血吸虫病防治杂志

Objective To understand the current status of capacity building in schistosomiasis control institutes in schistosomiasis-endemic provinces (municipality, autonomous region) of China. Methods The responsibilities and construction requirements of various schistosomiasis control institutions were surveyed by expert discussions, and field interviews and visits during the period between May and June, 2023, and the questionnaire for capacity maintenance and consolidation in schistosomiasis control institutions was designed. An online questionnaire survey was conducted in county-, municipal-, and provincial-level institutions that undertook schistosomiasis control and surveillance activities through the Wenjuanxing program. The distribution of schistosomiasis control institutions, the status of institutions, departments and staff undertaking schistosomiasis control activities and the translation of scientific researches on schistosomiasis control in China were analyzed. The laboratories accredited by China National Accreditation Service for Conformity Assessment (CNAS) were considered to be capable for testing associated with schistosomiasis control, and the testing capability of schistosomiasis control institutions was analyzed. Results A total of 486 valid questionnaires were recovered from 486 schistosomiasis control institutions in 12 endemic provinces (municipality, autonomous region) of China, including 12 provincial-level institutions (2.5%), 77 municipal-level institutions (15.8%) and 397 county-level institutions (81.7%). Of all schistosomiasis control institutions, 376 (77.4%) were centers for disease control and prevention or public health centers, 102 (21.0%) were institutions for schistosomiasis, endemic disease and parasitic disease control, and 8 (1.6%) were hospitals, healthcare centers or others. There were 37 713 active employees in the 486 schistosomiasis control institutions, including 5 675 employees related to schistosomiasis control, and the proportions of employees associated with schistosomiasis control among all active employees were 5.9% (231/3 897), 5.5% (566/10 134), and 20.6% (4 878/23 682) in provincial-, municipal-, and county-level institutions, respectively. There were 3 826 full-time employees working in schistosomiasis control activities, with 30.5% (1 166/3 826), 34.6% (1 324) and 34.9% (1 336/3 826) at ages of 40 years and below, 41 to 50 years and over 50 years, and there were 1 571 (41.0%) full-time schistosomiasis control employees with duration of schistosomiasis control activities for over 25 years, and 1 358 (35.5%) employees with junior professional titles and 1 290 with intermediate professional titles (35.5%), while 712 (18.6%) full-time employees working in schistosomiasis control activities had no professional titles. The three core schistosomiasis control activities included snail control (26.3%, 374/1 420), epidemics surveillance and management (25.4%, 361/1 420) and health education (18.8%, 267/1 420) in schistosomiasis control institutions. The Kato-Katz method, miracidium hatching test with nylon gauzes, and indirect haemagglutination assay (IHA) were the most commonly used techniques for detection of schistosomiasis, and there were less than 50% laboratories that had capabilities or experimental conditions for performing enzyme-linked immunosorbent assay (ELISA), dipstick dye immunoassay (DDIA), dot immunogold filtration assay (DIG-FA), loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR) assays. During the period from 2018 to 2022, schistosomiasis control institutions had undertaken a total of 211 research projects for schistosomiasis control, with a total funding of 18.596 million RMB, published 619 articles, participated in formulation of 13 schistosomiasis control-related criteria, and applied for 113 schistosomiasis control-related patents, including 101 that were granted, and commercialized 4 scientific research outcomes. Conclusions The proportion of independent specialized schistosomiasis control institutions is low in schistosomiasis control institutions in China, which suffers from problems of unsatisfactory laboratory testing capabilities, aging of staff and a high proportion of low-level professional titles. More investment into and intensified schistosomiasis control activities and improved capability building and talent cultivation in schistosomiasis control institutions are recommended to provide a powerful support for high-quality elimination of schistosomiasis in China.

Interpretation of the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) / 中国血吸虫病防治杂志

On June 16, 2023, National Disease Control and Prevention Administration of the People’s Republic of China, in collaboration with other ministries, formulated and issued the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030). The implementation of this plan provides an important basis for achieving the targets set in the “Healthy China 2030” action plan and the implementation of the rural revitalization strategy. This paper describes the background, principles, targets, control strategies, safeguard measures and effectiveness evaluation of the plan, in order to guide the scientific and standardized implementation of actions for schistosomiasis elimination at the grassroots level, and facilitate the progress towards elimination of schistosomiasis in China with a high quality.

High-quality acceleration of the Chinese national schistosomiasis elimination programme to advance the building of Healthy China / 中国血吸虫病防治杂志

The goal of achieving elimination of schistosomiasis across all endemic counties in China by 2030 was proposed in the Outline of the Healthy China 2030 Plan. On June 16, 2023, the Action Plan to Accelerate the Elimination of Schistosomiasis in China (2023—2030) was jointly issued by National Disease Control and Prevention Administration and other 10 ministries, which deployed the targets and key tasks of the national schistosomiasis elimination programme in China. This article describes the progress of the national schistosomiasis control programme, analyzes the opportunities to eliminate schistosomiasis, and proposes targeted recommendations to tackle the challenges of schistosomiasis elimination, so as to accelerate the process towards schistosomiasis elimination and facilitate the building of a healthy China.

Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants / 中华儿科杂志

Objective: To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI). Methods: This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1st, 2019 to December 31st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results: A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) (OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above (OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above (OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion: There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Influencing Factors of Cross-cultural Communication between Medical Professionals and Patients and Ways to Improve Competence / 中国医学伦理学

In order to build a global community of health for all, it is necessary to deeply understand the influencing factors of cross-cultural communication between medical professionals and patients. Factors such as different health beliefs, cultural values and communication mediators influence cross-cultural communication between medical professionals and patients, and then affect the medical satisfaction and treatment compliance. Medical education should adopt the learning concept of constructivism, advocate maintaining a humble cultural attitude, incorporate more patient perspectives and adopt cross-cultural teaching mode to improve the cross-cultural communication competence of medical students and medical staff, so as to establish a relationship based on communication and understanding.

A Case Report of MYH9 Gene Mutation Associated with Glomerular Minor Lesion / 罕见病研究

Non-muscle myosin heavy chain 9-related disease (MYH9-RD) is an autosomal dominant disease caused by the mutations of the MYH9 gene encoding the non-muscle mysoin heavy chain ⅡA and leads to abnormal accumulation of myosin in cells. These further causes functional disorders of the blood, eye, ear, kidney, and liver systems. MYH9-RD displays heterogeneous kidney involvement and outcomes, but doctors still lack understandings of the mechanism and treatment strategies, owing to difficulty of conducting renal biopsies. Here, we report a case of MYH9-RD with tail fragments heterozygous mutation, which renal pathology is presented as glomerular minor lesion. Moreover, we reviewed related relevant to strengthen clinical diagnosis and understanding of MYH9-RD.

Recent advances of antiviral drugs based on multispecific binding strategy / 药学学报

To address the continuous emergence of drug-resistant strains of viruses and the outbreaks of novel virus infections, developing new antiviral drugs based on novel strategies has become an important and urgent research topic. In recent years, the rapidly developing multi-specific binding strategy has become a focus and been widely applied in antiviral. This review summarizes the recent progress of the multi-specific binding strategy in the antiviral field from the perspective of medicinal chemistry and discusses existing challenges as well as future opportunities for antiviral drug discovery.

Recent advances of small molecule inhibitors directly targeting HBV / 药学学报

Hepatitis B virus infection is a serious threat to human life and health. The approved anti-HBV drugs including interferons and nucleos(t)ide analogues have serious adverse effect, rebound phenomena after drug withdrawal, and drug resistance. And the cccDNA cannot be completely eliminated by both of them, which is the reason why a complete cure for hepatitis B cannot be achieved. Therefore, developing anti-HBV drugs directly targeting protein or nucleic acid of HBV remains a current public health priority. Based on the analysis of representative literature from the last decade, this article reviews recent developments in small molecule inhibitors directly targeting HBV from a medicinal chemistry perspective.

Advances in research on small molecule regulators targeting HBV cccDNA generation and transcription / 药学学报

Hepatitis B virus (HBV) represents a significant global public health challenge. Despite the availability of several approved drugs for hepatitis B treatment, the persistence of covalently closed circular DNA (cccDNA) renders HBV eradication elusive, thereby leading to disease relapse after drug withdrawal. This paper reviews the regulatory mechanisms of cccDNA formation, transcription and replication, and summarizes the research progress of related small molecule regulators from the perspective of medicinal chemistry.

Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention / 老年心脏病学杂志（英文版）

OBJECTIVE@#To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI).@*METHODS@#A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581).@*RESULTS@#Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371).@*CONCLUSIONS@#For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Therapeutic effect of ursodeoxycholic acid-berberine supramolecular nanoparticles on ulcerative colitis based on supramolecular system induced by weak bond / 中国中药杂志

Ulcerative colitis(UC) is a recurrent, intractable inflammatory bowel disease. Coptidis Rhizoma and Bovis Calculus, serving as heat-clearing and toxin-removing drugs, have long been used in the treatment of UC. Berberine(BBR) and ursodeoxycholic acid(UDCA), the main active components of Coptidis Rhizoma and Bovis Calculus, respectively, were employed to obtain UDCA-BBR supramolecular nanoparticles by stimulated co-decocting process for enhancing the therapeutic effect on UC. As revealed by the characterization of supramolecular nanoparticles by field emission scanning electron microscopy(FE-SEM) and dynamic light scattering(DLS), the supramolecular nanoparticles were tetrahedral nanoparticles with an average particle size of 180 nm. The molecular structure was described by ultraviolet spectroscopy, fluorescence spectroscopy, infrared spectroscopy, high-resolution mass spectrometry, and hydrogen-nuclear magnetic resonance(H-NMR) spectroscopy. The results showed that the formation of the supramolecular nano-particle was attributed to the mutual electrostatic attraction and hydrophobic interaction between BBR and UDCA. Additionally, supramolecular nanoparticles were also characterized by sustained release and pH sensitivity. The acute UC model was induced by dextran sulfate sodium(DSS) in mice. It was found that supramolecular nanoparticles could effectively improve body mass reduction and colon shortening in mice with UC(P<0.001) and decrease disease activity index(DAI)(P<0.01). There were statistically significant differences between the supramolecular nanoparticles group and the mechanical mixture group(P<0.001, P<0.05). Enzyme-linked immunosorbent assay(ELISA) was used to detect the serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6), and the results showed that supramolecular nanoparticles could reduce serum TNF-α and IL-6 levels(P<0.001) and exhibited an obvious difference with the mechanical mixture group(P<0.01, P<0.05). Flow cytometry indicated that supramolecular nanoparticles could reduce the recruitment of neutrophils in the lamina propria of the colon(P<0.05), which was significantly different from the mechanical mixture group(P<0.05). These findings suggested that as compared with the mechanical mixture, the supramolecular nanoparticles could effectively improve the symptoms of acute UC in mice. The study provides a new research idea for the poor absorption of small molecules and the unsatisfactory therapeutic effect of traditional Chinese medicine and lays a foundation for the research on the nano-drug delivery system of traditional Chinese medicine.

Effects and mechanisms of curcumin on apoptosis of retinal ganglion cells in chronic ocular hypertension rats / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effects and mechanisms of curcumin on apoptosis of retinal ganglion cells(RGCs)in chronic ocular hypertension rats.METHODS:A total of 21 Spraque-Dawley(SD)rats were randomly divided into 3 groups with 7 rats in each group. The rat models of chronic ocular hypertension were established by cauterization of the superior scleral veins in the high intraocular pressure model group and the curcumin treatment group, and the sham operation group only cut the conjunctiva without the cauterization of the superior scleral veins; the rats in the curcumin treatment group were intragastrically treated with curcumin at a dose of 4mL/kg, and the rats in the sham operation group and the high intraocular pressure model group were treated with pure water at a dose of 4mL/kg for 3wk. After 3wk, HE staining was used to observe the morphological and pathological changes of retina, the number of RGCs and the thickness of ganglion cell layer(GCL)in each group of rats; TUNEL staining was used to observe the apoptosis of RGCs and retinal cells in each group of rats; the expression levels of glutamate-cysteine ligase modifier subunit(GCLM)and heme oxygenase-1(HO-1)in the retina of each group of rats were detected by real-time fluorescence quantitative PCR, immunohistochemical staining and Western blot.RESULTS:Compared with the sham operation group, the retinal morphology of rats in the high intraocular pressure model group and the curcumin treatment group was disorganized, the number of RGCs was reduced, the GCL was thinner, the apoptosis rate of RGCs and retinal cells increased, and the expression levels of GCLM and HO-1 increased. Compared with the high intraocular pressure model group, the retinal morphology of rats in the curcumin treatment group was basically normal, the number of RGCs increased, the GCL thickened, the apoptosis rate of RGCs and retinal cells decreased, and the expression levels of GCLM and HO-1 increased.CONCLUSION:Curcumin can inhibit the apoptosis of RGCs in the rat model of chronic ocular hypertension by up-regulating the expression of antioxidant genes GCLM and HO-1.

An excerpt of EASL clinical practice guidelines on the management of liver diseases in pregnancy （2023） / 临床肝胆病杂志

Recently， the European Association for the Study of the Liver organized the development of the clinical practice guidelines for the management of liver diseases in pregnancy， which include 105 recommendations for the clinical management of liver diseases in pregnancy. This article gives an excerpt of the main contents of the guidelines.

Naoxintong Capsules Treat Cardiac Injury after Cerebral Ischemia via TLR2/TLR4 Signaling Pathway / 中国实验方剂学杂志

ObjectiveAfter the brain and heart injuries were simulated by myocardial injury caused by acute cerebral ischemia， this study explored the mechanism of Naoxintong capsules in treating brain and heart injuries under cerebral ischemia state with Toll-like receptor （TLR） 2/TLR4 as the breakthrough point. MethodC57BL/6 male mice were randomly assigned into the sham operation， model， Naoxintong， and Ginaton groups. The middle cerebral artery occlusion （MCAO） method was used to establish a mouse model of cerebral ischemia. The neuroethological score， cerebral infarction area， cell apoptosis， ionized calcium-binding adaptor molecule 1 （IBA-1）-positive microglia proportion， and serum levels of N-terminal pro-brain natriuretic peptide （NT-proBNP）， creatine kinase-MB （CK-MB）， and lactic dehydrogenase （LDH） were determined to evaluate the pharmacodynamic effects of Naoxintong capsules on heart and brain injuries after cerebral ischemia in mice. Western blotting was employed to determine the expression of TLR2/TLR4 protein in the brain and heart of mice. ResultCompared with the sham operation group， the model group showed increased cerebral infarction area， neuroethological score， apoptosis rate， IBA-1-positive microglia proportion， and serum levels of NT-proBNP， CK-MB， and LDH （P<0.01）. Naoxintong capsules reduced the cerebral infarction area， neuroethological score， apoptosis rate， IBA-1-positive microglia proportion （P<0.01）， and serum NT-proBNP and CK-MB levels （P<0.05） in mice compared with the model group. Western blotting results showed that Naoxintong Capsules down-regulated the expression levels of TLR2 （P<0.05） in the brain and TLR2 （P<0.01） and TLR4 （P<0.05） in the heart. ConclusionCerebral ischemia can cause myocardial damage， reflecting the pathological process of cardiac injury after cerebral ischemia. Naoxintong capsules can mitigate brain and heart injuries after cerebral ischemia and achieve the simultaneous treatment of the brain and the heart， in which TLR2/TLR4 plays a role.

Progress of circulating tumor DNA in cervical cancer / 肿瘤研究与临床

Cervical cancer is a leading cause of cancer death in women. There are no reliable noninvasive indicators to predict the recurrence, metastasis and prognosis of cervical cancer. Circulating tumor DNA (ctDNA) is a kind of DNA fragment released from tumor cells into the blood circulation, which has the advantages of being non-invasive, real-time, and of reflecting the genetic characteristics of tumors. With the improvement of ctDNA detection technology and in-depth research on ctDNA, ctDNA has shown more obvious advantages in early diagnosis, tumor molecular typing, treatment monitoring and recurrence prediction of cervical cancer compared with traditional histological, serological and imaging detection methods. This paper reviews the detection methods of ctDNA and its latest research progress of ctDNA in cervical cancer.

Efficacy and safety of image-guided hypofractionated intensity-modulated radiotherapy combined with contralateral esophageal protection in treatment of unresectable stage Ⅲ non-small cell lung cancer / 肿瘤研究与临床

Objective:To explore the efficacy and adverse reactions of image-guided hypofractionated intensity-modulated radiotherapy (Ig-HypoRT) conbined with contralateral esophageal protection in treatment of patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC).Methods:The clinical data of 45 patients with unresectable stage Ⅲ NSCLC who were admitted to Xuzhou Cancer Hospital from January 2016 to January 2019 were retrospectively analyzed. Patients received induction chemotherapy with a platinum-based dual-drug combination regimen, followed by Ig-HypoRT with a total dose of tumor of 60-63 Gy/12- 18 times at 3.5-5.0 Gy/time. Contralateral esophagus was delineated as an organ at risk during radiotherapy, limiting V 45 Gy≤1.8 cc and V 55 Gy ≤0.4 cc. Patients' efficacy, survival and the occurrence of adverse reactions were observed. Results:Among 45 patients, there were 9 cases of complete remission, 31 cases of partial remission, 4 cases of stable disease and 1 case of disease progression, and the effective rate was 88.8% (40/45). The median follow-up time was 34 months, 45 patients had a median overall survival (OS) time of 25.0 months (95% CI 21.7-28.8 months), with 1-, 2-, and 3-year OS rates of 78.9%, 56.8% and 47.7%, respectively; the median progression-free survival (PFS) time was 18.5 months (95% CI 15.0-22.0 months), with 1-, 2- and 3-year PFS rates of 59.8%, 32.6% and 18.6%, respectively. The 3-year local recurrence rate was 9% (4/45). The incidence of grade 1-2 radioactive esophagitis was 80% (36/45); the incidence of grade 1-2 chest pain was 20% (9/45). The incidence of grade 3-4 adverse reactions were 13% (6/45), including 7% (3/45) of grade 3 pulmonary atelectasis, 4% (2/45) of grade 3 radioactive pneumonia, and 2% (1/45) of grade 4 hemoptysis. Conclusions:Ig-HypoRT combined with contralateral esophageal protection for unresectable stage Ⅲ NSCLC can improve survival rate and reduce esophageal adverse reactions of patients.

Randomized controlled trials of acupuncture for the treatment of essential hypertension:a meta-analysis / 针灸推拿医学（英文版）

Objective:To systematically assess the efficacy and safety of acupuncture therapy for essential hypertension.Methods:A computerized literature search of the Chinese National Knowledge Infrastructure(CNKI),Chongqing VIP Database(CQVIP),Wanfang Academic Journal Full-text Database(Wanfang),China Biology Medicine Disc(CBM),PubMed,Excerpta Medica Database(EMBASE),and Cochrane Library was conducted to retrieve randomized controlled clinical trials on acupuncture as the main intervention for the treatment of essential hypertension published from the inception of the database to 30 January 2021.The risk-of-bias assessment was carried out for each included study according to the Cochrane Handbook.Data analysis was performed using Review Manager 5.4.1 and Stata 15.0.Results:After the screening,46 randomized controlled trials involving a total of 3 859 subjects were included.Primary outcomes included changes in the diastolic blood pressure after intervention[eight studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[mean difference(MD)=1.45,95%confidence interval(CI)(0.48,2.43),P=0.004,fixed effects model;I2=39%]and changes in the systolic blood pressure after intervention{11 studies showed that the acupuncture plus antihypertensive drug group was better than the antihypertensive drug monotherapy group[MD=8.60,95%CI(7.12,10.07),P<0.00001,fixed effects model;I2=26%]}.The secondary outcome was antihypertensive efficacy,12 studies of acupuncture monotherapy group[risk ratio(RR)=1.20,95%CI(1.12,1.28),P<0.00001,fixed effects model;I2=36%]and 15 studies of acupuncture combined with antihypertensive drug group[RR=1.27,95%CI(1.20,1.34),P<0.00001,fixed effects model;I2=6%]showed better results than the antihypertensive drug monotherapy group in antihypertensive efficacy.In terms of the adverse events,four studies showed that the acupuncture monotherapy group had fewer adverse events than the antihypertensive drug monotherapy group[RR=0.10,95%CI(0.04,0.25),P<0.00001,fixed effects model;I2=0%].Conclusion:Acupuncture combined with antihypertensive drugs is superior to antihypertensive drugs alone in reducing blood pressure,and acupuncture therapy is effective and safe for the treatment of essential hypertension with fewer side effects.However,there is still a lack of high-quality multicenter randomized double-blinded controlled trials in this field.Rigorous large-sample clinical trials are needed to validate these findings.