Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement / 国际口腔科学杂志·英文版

Pyroptosis, an inflammatory caspase-dependent programmed cell death, plays a vital role in maintaining tissue homeostasis and activating inflammatory responses. Orthodontic tooth movement (OTM) is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament (PDL) progenitor cells. However, whether and how force induces PDL progenitor cell pyroptosis, thereby influencing OTM and alveolar bone remodeling remains unknown. In this study, we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling process. Blocking or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling respectively. Using Caspase-1-/- mice, we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on Caspase-1. Moreover, mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro, which influenced osteoclastogenesis. Mechanistically, transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor cells. Overall, this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli, indicating a promising approach to accelerate OTM by targeting Caspase-1.

A descriptive analysis of hyperlipidemia in adult twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.

A descriptive analysis on hypertension in adult twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.

Response characteristics of tislelizumab combined with chemotherapy in first-line treatment of locally advanced or metastatic non-squamous non-small cell lung cancer / 中华肿瘤杂志

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Progress in Research and Application of CAR-T Cell Therapy in T-Lymphocyte Tumors --Review / 中国实验血液学杂志

T-lymphocyte tumors are a group of diseases containing various types of lymphatic system tumors, with strong heterogeneity and poor clinical outcomes. Chimeric antigen receptor T (CAR-T) cell therapy, as a new immune cell therapy, has made a breakthrough in the field of B-lymphocyte tumors. People are interested in the application prospect of this technique in the field of T-lymphocyte tumors. Some studies have shown that CAR-T cell therapy has made some progress in the treatment of T-lymphocyte tumors, and CAR-T for some targets has entered the stage of clinical trials. However, due to the characteristics of T cells, there are also many challenges. This article reviews the research and application of CAR-T cell therapy in T-lymphocyte tumors.

Efficacy and Survival of Venetoclax Based Regimen in the Treatment of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）.@*METHODS@#A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed.@*RESULTS@#A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients.@*CONCLUSION@#VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.

Establishment of contralateral arteriovenous fistula by using the waste vein on the side of central venous lesion: a case report / 中华肾脏病杂志

Central venous lesion is a difficult problem in the vascular access complications of hemodialysis, which can cause serious clinical symptoms and affect the quality of hemodialysis and life of patients. We established arteriovenous fistula of the contralateral graft blood vessel with the used vein on the diseased side of the central vein of the patient. The arteriovenous fistula of the graft blood vessel was successfully punctured and hemodialysis was performed 2 weeks later. In this way, we not only solved the problem of venous hypertension and subsequent vascular access in the patient, but also reserved more vascular resources.

Telbivudine-Induced Myopathy: Clinical Features, Histopathological Characteristics, and Risk Factors

Background@#and Purpose Oral nucleos(t)ide analogs (NAs) are the mainstay treatment for chronic hepatitis B (CHB). Myotoxicity is an important extrahepatic effect related to NA treatment. Telbivudine is the NA for CHB that is frequently associated with muscle-related side effects. The risk factors for telbivudine-induced myopathy (TIM) are not yet clear. @*Methods@#This study characterized the clinical, magnetic resonance images (MRI), and pathological features of 12 TIM cases. A group of telbivudine-tolerant (TT) patients with CHB who received regular telbivudine treatment during the same period without the occurrence of myopathy was collected. Demographic and clinical factors were compared between the patients with TIM and the TT controls. Factors independently associated with TIM were identified using logistic regression analysis. @*Results@#The patients with TIM (males/females: 7/5, mean age: 57 years) developed myopathy after using telbivudine for a median period of 19.5 months. Muscle histopathology revealed abnormal proliferation, subsarcolemmal or sarcoplasmic accumulations, and ultrastructural defects of mitochondria. When compared with TT cases, patients with TIM had a lower estimated glomerular filtration rate and were more frequently positive for hepatitis B e antigen (HBeAg). @*Conclusions@#Mitochondrial abnormalities are characteristic histopathological features, and impaired renal function and HBeAg positivity are risk factors for TIM. Telbivudine-induced mitochondrial dysfunction and immune activation related to mitochondrial damage and HBeAg serostatus changes may underlie TIM. Constant clinical surveillance of myopathy during telbivudine treatment is needed due to the significant latency of its development. Dose adjustment for impaired renal function does not eliminate the risk of TIM occurrence.

Craniofacial anatomical Characteristics of patients with catathrenia / 中华口腔医学杂志

Objective: To analyze whether the upper airway of patients with catathrenia has obstructive manifestations using nasal resistance, craniofacial, and upper airway imaging methods, which could benefit the exploration of the etiology and treatment options. Methods: From August 2012 to September 2019, a total of 57 patients with catathrenia in the Department of Orthodontics at Peking University Hospital of Stomatology were included in the study, including 22 males and 35 females, aged (31.1±10.9) years, with a body mass index of (21.7±2.7) kg/m2. All the patients were diagnosed by full-night polysomnography at the Sleep Division, Peking University People's Hospital, of which 10 patients were combined with obstructive sleep apnea hypopnea syndrome (OSAHS). The median groaning index of patients was 4.8 (1.8, 13.0) events/h. Nasal resistance and cone-beam CT were conducted on the patients, and measurements were performed on the craniofacial structures, upper airway, and surrounding soft tissues, compared with non-snoring normal occlusion individuals' references published by the same research team (144 college students recruited at Peking University and 100 non-snoring young adults with normal occlusion recruited at six universities in Beijing). Results: The total nasal resistance of patients with catathrenia was (0.26±0.08) Pa·cm-3·s-1. The patients had overall well-developed mandibular hard tissues. However, the patients were found with increased FH/BaN (steep anterior cranial base plane), increased MP/FH (forward rotation of the mandible); increased U1/NA and L1/MP (proclined upper and lower incisors). The sagittal diameter of the velopharynx [(19.2±4.5) mm] was significantly larger than the normal reference (t=8.44, P<0.001), while the sagittal diameter at the hypopharynx [(17.4±6.4) mm] was statistically smaller than the normal reference (t=-2.79, P=0.006). Catarhrenia patients combined with OSAHS presented longer soft palate, tongue, and lower hyoid bone than those with primary catathrenia. Conclusions: In patients with catathrenia, the overall craniofacial characteristics are well-developed skeletal structures, lower nasal resistance, proclined upper and lower incisors, wide upper sagittal development of the upper airway and narrow hypopharynx. Groaning sounds might be related to the narrowing of the hypopharynx during sleep.

The research of liver failure in Banna miniature pigs caused by amanita exitialis / 中华劳动卫生职业病杂志

Objective: To explore the characteristics of Banna miniature pig liver failure induced by amanita exitialis. Methods: From September to October 2020, a reverse high performance liquid chromatography (RP-HPLC) method was used to determine the toxin content of amanita exitialis solution, and 2.0 mg/kg amanita exitialis solution (α-amanitins+β-amanitins) was administered orally to Banna miniature pigs. Toxic symptoms, blood biochemical indexes and histopathological changes of liver, heart and kidney were observed at each time point. Results: All Banna miniature pigs died within 76 h of exposure, and different degrees of digestive tract symptoms such as nausea, vomiting and diarrhea appeared between 6 and 36 h. The biochemical indexes of alanine aminotransferase, aspartate aminotransferase, total bilirubin, lactate dehydrogenase, myoglobin, creatine kinase isoenzyme, blood urea nitrogen and creatinine increased significantly at 52 h after exposure, and the differences were statistically significant compared with 0 h (P<0.05). The bleeding of liver and heart was obvious under macroscopic and microscopic observation, hepatocyte necrosis, renal tubule epithelial cell swelling. Conclusion: Large dose of amanita exitialis can cause acute liver failure of Banna miniature pigs, which is in line with the pathophysiological characteristics of acute liver failure, and lays a foundation for further research on the toxic mechanism and detoxification drugs of amanita exitialis induced liver failure.

Guanxinning Tablet and their active substances alleviate ox-LDL-induced endothelial cell injury / 药学学报

This study investigated the intervention effect of Guanxinning Tablet on human umbilical vein endothelial cells (HUVECs) injury induced by oxidized low density lipoprotein (ox-LDL), providing experimental basis for Guanxinning Tablet in the treatment of atherosclerosis-related diseases. Under the damage of HUVECs by ox-LDL, the cell viability was detected by CCK-8 (cell counting kit-8) assay; lactate dehydrogenase (LDH) in the cell culture supernatant was detected by the corresponding kit; the cell morphology of different groups was observed by common phase contrast microscope; reactive oxygen species (ROS) and NO levels in the cells were detected by DCFH-DA and DAF-FM DA probes, respectively; monocyte adhesion assay was used to detect the recruitment of THP-1 in HUVECs, and TMRM dye was used to detect the level of mitochondrial membrane potential; interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) secretion in the cells was detected by ELISA assay. The results showed that Guanxinning Tablet had a concentration-dependent proliferative effect on HUVECs. Under the stimulation of 100 μg·mL-1 ox-LDL, the morphology of endothelial cells was significantly changed. At this time, NO level was significantly decreased, ROS level was significantly increased and accompanied by a decrease in mitochondrial membrane potential. The recruitment of THP-1 cells by endothelial cells and IL-6, ICAM-1 and MCP-1 were also significantly increased, resulting in oxidative stress and inflammatory injury. Guanxinning Tablet and its composed extracts could significantly improve cell morphology, increase NO level, decrease ROS production, and also reduce the secretion of inflammation-related proteins IL-6 and MCP-1. Salvia miltiorrhiza and Ligusticum striatum DC. have significant synergistic effects on NO. Among them, salvianolic acid B and salvianic acid A exerted the main effects, and the combined efficacy of salvianic acid A and ferulic acid was superior to that of single administration. The above results showed that Guanxinning Tablet and their active substances had the effects of improving endothelial basal function, resisting oxidative stress, and alleviating inflammatory injury, and Salvia miltiorrhiza and Ligusticum striatum DC. synergized, which may be related to their regulation of oxidative stress and inflammation and have application prospects in the treatment of atherosclerosis-related diseases.

Establishment of contralateral arteriovenous fistula by using the waste vein on the side of central venous lesion: a case report / 中华肝脏病杂志

Central venous lesion is a difficult problem in the vascular access complications of hemodialysis, which can cause serious clinical symptoms and affect the quality of hemodialysis and life of patients. We established arteriovenous fistula of the contralateral graft blood vessel with the used vein on the diseased side of the central vein of the patient. The arteriovenous fistula of the graft blood vessel was successfully punctured and hemodialysis was performed 2 weeks later. In this way, we not only solved the problem of venous hypertension and subsequent vascular access in the patient, but also reserved more vascular resources.

Investigation on a case of Amanita neoovoidea poisoning / 中华劳动卫生职业病杂志

This paper reported a case of poisoning caused by ingestion of Amanita neoovoidea. The patient experienced nausea, vomiting, oliguria, acute renal function injury, and was discharged after symptomatic support treatment and blood purification treatment. Given the different toxicity of different mushrooms, species identification of poisonous mushrooms can help clinicians in diagnosis and treatment.

Construction of AQHI based on joint effects of multi-pollutants in 5 provinces of China / 环境与职业医学

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO2, NO2, CO, PM2.5, PM10, and maximum 8 h O3 concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM2.5, NO2, SO2, and O3 were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM2.5, NO2, SO2 and O3 were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Physiologic and epigenetic effects of nutrients on disease pathways

BACKGROUND/OBJECTIVES@#Epigenetic regulation by nutrients can influence the development of specific diseases. This study sought to examine the effect of individual nutrients and nutrient families in the context of preventing chronic metabolic diseases via epigenetic regulation. The inhibition of lipid accumulation and inflammation by nutrients including proteins, lipids, vitamins, and minerals were observed, and histone acetylation by histone acetyltransferase (HAT) was measured. Correlative analyses were also performed.MATERIALS/METHODS: Nutrients were selected according to information from the Korean Ministry of Food and Drug Safety. Selected nutrient functionalities, including the attenuation of fatty acid-induced lipid accumulation and lipopolysaccharide-mediated acute inflammation were evaluated in mouse macrophage Raw264.7 and mouse hepatocyte AML-12 cells. Effects of the selected nutrients on in vitro HAT inhibition were also evaluated. @*RESULTS@#Nitric oxide (NO) production correlated with HAT activity, which was regulated by the amino acids group, suggesting that amino acids potentially contribute to the attenuation of NO production via the inhibition of HAT activity. Unsaturated fatty acids tended to attenuate inflammation by inhibiting NO production, which may be attributable to the inhibition of in vitro HAT activity. In contrast to water-soluble vitamins, the lipid-soluble vitamins significantly decreased NO production. Water- and lipid-soluble vitamins both exhibited significant inhibitory activities against HAT. In addition, calcium and manganese significantly inhibited lipid accumulation, NO production, and HAT activity. @*CONCLUSIONS@#Several candidate nutrients and their family members may have roles in the prevention of diseases, including hepatic steatosis and inflammation-related diseases (i.e., nonalcoholic steatohepatitis) via epigenetic regulation. Further studies are warranted to determine which specific amino acids, unsaturated fatty acids and lipid-soluble vitamins or specific minerals influence the development of steatosis and inflammatory-related diseases.

Research advances on extracellular vesicles-based regulation by traditional Chinese medicines and the relationship with TCM "Qi" / 药学学报

Extracellular vesicles (EVs) are an important type of active microvesicles. EVs encapsulate and transfer functional substances such as miRNAs, transcription factors and proteins, which are important vectors for cell communication and organ dialogue. In recent years, studies have shown that quite a number of Chinese medicinal herbs have the pharmacological effect of regulating EVs, and play a unique trans-organ and remote role in the treatment of diseases. Some Chinese medicinal herbs also contain plant-derived EVs themselves, which can be directly involved in the treatment of diseases. As one of the core theories of raditional Chinese medicines (TCM), Qi plays a variety of important roles in the physiological and pathological processes of human body and pharmacology. However, the scientific connotation of Qi′s role and the potential material carrier are still unclear. The latest research suggests that the effect of EVs is potentially related to that of Qi. Therefore, this paper reviews the effect of Qi nourishing Chinese medicinal herbs in regulating EVs in the treatment of cardiovascular diseases, nervous system diseases, liver diseases, renal diseases, malignant tumors and other diseases in recent years. EVs may play an important role in the pharmacological effect of some Chinese medicinal herbs in the treatment of diseases as an intermediary substance. EVs have the characteristics of long-distance transportation, which is consistent with the movement of Qi in TCM. EVs carry a variety of functional molecules, which is consistent with the function of Qi. As the potential material basis of Qi in TCM, the function of EVs is worth further study.

Development and Validation of a Predictive Risk Model for Vision-threatening Diabetic Retinopathy in Patients with Type 2 Diabetes / 中山大学学报(医学科学版)

ObjectiveTo develop and validate a predictive risk model for vision-threatening diabetic retinopathy in patients with type 2 diabetes using readily accessible clinical data， which may provide a convenient and effective prediction tool for early identification and referral of at-risk populations. MethodsA nomogram model was developed using a dataset obtained from patients with T2DM who participated in the Guangzhou Diabetic Eye Study from November 2017 to December 2020. Logistic regression was used to construct the model， and model performance was evaluated using receiver operating characteristic curve， Hosmer-Lemeshow test， calibration curve and decision curve analysis. The model underwent internal validation through the mean AUC of k-fold cross-validation method， and further external validation was conducted in the Dongguan Eye Study. ResultsA total of 2 161 individuals were included in the model development dataset， of whom 135 （6.25%） people were diagnosed with VTDR. Age （P＜0.001，OR=0.927，95%CI：0.898~0.957） and body mass index （P＜0.001，OR =0.845，95%CI：0.821~0.932） were found to be negatively correlated with VTDR， whereas diabetes duration （P＜0.001，OR=1.064，95%CI：1.035~1.094）， insulin use （P =0.045，OR =1.534，95%CI：1.010~2.332）， systolic blood pressure （P＜0.001，OR =1.019，95%CI：1.008~1.029）， glycated hemoglobin （P＜0.001，OR =1.484，95%CI：1.341~1.643）， and serum creatinine （P＜0.001，OR =1.017，95%CI：1.010~1.023） were positively correlated with VTDR. All these variables were included in the model as predictors. The model showed strong discrimination in the development dataset with an area under the receiver operating characteristic curve （AUC） of 0.797 and in the external validation dataset （AUC 0.762）. The Hosmer-Lemeshow test（P＞0.05）and the calibration curve displayed good agreement. Decision curve analysis showed that the nomogram produced net benefit in the two datasets. ConclusionsIndependent factors influencing VTDR include age， duration of diabetes mellitus， insulin use， body mass index， systolic blood pressure， glycosylated hemoglobin， and serum creatinine. The nomogram constructed using these variables demonstrates a high degree of predictive validity. The model can serve as a valuable tool for early detection and referral of VTDR in primary care clinics. Therefore， its application and promotion are highly recommended.

Screening of anti-SARS-CoV-2 ligands from Chinese herbs based on a dual-target surface plasmon resonance biosensor / 药学学报

The epidemic of COVID-19 has brought great challenges to the global public health prevention and control system combined with clinical diagnosis and treatment system, and it makes the development of effective antiviral drugs an important task in current pharmaceutical research. Traditional Chinese medicine (TCM) has played an important role in the prevention and control of COVID-19. Due to its numerous chemical components and various structural types, TCM becomes a natural library for searching for lead compounds against SARS-CoV-2. In this study, a novel dual-target surface plasmon resonance (SPR) biosensor was developed for S protein receptor binding domain (SRBD) and angiotensin converting enzyme 2 (ACE2) which are two key proteins in the process of SARS-CoV-2 invading cells according to characteristics of synergistic effects of multiple components and comprehensive regulation of multiple targets of TCM. The SPR biosensor was applied to screen and identify active components from six TCMs, and daidzin from Puerariae Lobatae Radix was identified to bind with SRBD and ACE2. The affinity constant (KD) of daidzin and ACE2 was 5.18 μmol·L-1 through the SPR affinity assay. Competitive ELISA assay showed that daidzin could inhibit the binding of SRBD and ACE2, and the inhibition rate of daidzin (20 μmol·L-1) was 38.6%. Molecular docking experiments further confirmed that daidzin had the best binding near the binding region of SRBD-ACE2 complex. This study shows that the dual-target SPR screening system is accurate and efficient, and is particularly suitable for screening of complex drug systems and effective substances study of TCM. It provides a material basis for exploring the mechanism of TCM active constituents against SARS-CoV-2, and provides a source of lead compounds for the development of anti-SARS-CoV-2 drugs.

Study on the risk and countermeasure of prescription drugs sold online by drug retail enterprises / 中国药房

OBJECTIVE To analyze the risks of prescription drugs sold online by drug retail enterprises， and to provide countermeasures and suggestions for risk prevention and control of prescription drugs sold online. METHODS The risk hierarchy structure model of prescription drugs sold online by drug retail enterprises was constructed by using analytic hierarchy process. Multiple rounds of risk research and judgment were carried out on 123 pairs of evaluation indicators by using Delphi expert survey method. The normalized weight calculation and consistency test of risk judgment matrix were carried out to perform fuzzy quantitative research. RESULTS The risk of prescription dispensing and review （6.48%）， the risk of drug first and prescription later （5.48%）， the risk of rational drug use guidance （4.99%）， the risk of buying drugs by abnormal channel （4.97%）， the risk of “first diagnosis， non-chronic disease and non-common disease” （4.43%）， and the quality and safety risk of returned drugs （4.34%） and the application risk of regulatory technology （4.06%） were high risks； the overall risk of drug retail enterprises （chain） selling prescription drugs online was 38.67%， and the overall risk of drug retail enterprises （individual） selling prescription drugs online was 61.33%， with a difference of 22.66% between them. CONCLUSIONS There were 7 high-risk indicators for prescription drugs sold online by drug retail enterprises. Among them， the risk of prescription dispensing and review， the risk of drug first and prescription later， and the risk of rational drug use guidance are the top three high-risk points. The risk of prescription drugs sold online by drug retail enterprises （individual） is higher than that of drug retail enterprises （chain）. It is recommended that regulatory authorities focus on and regulate the prescription drugs sold online by drug retail enterprises （individual）， and encourage drug retail enterprises （chain） to establish a systematic online sales process for prescription drugs； for high-risk points of prescription drugs sold online， it is recommended that regulatory authorities and drug retail enterprises focus on it and take effective risk prevention and control measures to ensure the safe use of prescription drugs by the general public.

The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo / 中西医结合学报

OBJECTIVE@#Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy.@*METHODS@#The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression.@*RESULTS@#rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity.@*CONCLUSION@#Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.