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BACKGROUND: The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. We aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC > 7.0 cm accompanied with major PVTT. MATERIALS AND METHODS: This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score-matching (PSM). RESULTS: A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524). CONCLUSION: The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

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ObjectiveTo explore the application effect of Jianpi Huoxue prescription combined with acupuncture in patients with chronic atrophic gastritis （CAG） of gastric blood stasis type. MethodA total of 86 patients with CAG admitted to Wuhan First Hospital from November 2021 to March 2023 were selected and randomly divided into two groups. The control group was treated with conventional Western medicine， while the observation group was treated with Jianpi Huoxue prescription combined with acupuncture. The clinical efficacy， traditional Chinese medicine （TCM） syndrome score， pathological score， negative conversion rate of Helicobacter pylori （Hp）， inflammatory indicators ［neutrophils/lymphocytes （NLR） and interleukin （IL）-1β］， changes in levels of gastric protease （PG） Ⅰ， PG Ⅰ/PG Ⅱ， and gastrin-17 （G-17）， and drug safety during treatment were observed after treatment in both groups. ResultAfter treatment， the total effective rate of the observation group ［95.35% （41/43）］ was significantly better than that of the control group ［79.07% （34/43）］， and the difference was statistically significant （χ2=5.108， P<0.05）. After treatment， the scores of the primary and secondary TCM syndromes in the observation group and the control group were significantly decreased （P<0.05）. After treatment， the scores of primary and secondary TCM syndromes in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the pathological scores of gastric mucosa atrophy， activity， chronic inflammation， intestinal metaplasia， and dysplasia were significantly lower in the observation group and control group （P<0.05）. After treatment， the pathological scores of gastric mucosa atrophy， activity， chronic inflammation， intestinal metaplasia， and dysplasia in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the Hp conversion rate in the observation group was significantly increased compared with the control group （P<0.05）. After treatment， the levels of inflammatory indicators NLR and IL-1β in the observation group and control group were significantly lower （P<0.05）， and the levels of inflammatory indicators NLR and IL-1β in the observation group were significantly lower than those in the control group （P<0.05）. After treatment， the levels of PGI and PGⅠ/PGⅡ in the observation group and control group were significantly higher （P<0.05）， and the levels of PGI and PGⅠ/PGⅡ in the observation group were significantly higher than those in the control group （P<0.05）. After treatment， the G-17 level of the observation group and the control group was different at different time points （P<0.05）， and the G-17 level of the observation group was higher at different time points than that of the control group （P<0.05）. The G-17 level of the observation group had an increasing trend compared with the control group （P<0.05）. There was no significant difference in the risk of adverse reactions between the two groups. ConclusionThe combination of Jianpi Huoxue prescription and acupuncture can effectively alleviate symptoms， increase Hp negative conversion rate， inhibit inflammation， and regulate PG and G-17 levels in CAG patients， thus controlling or even reversing gastric mucosal atrophy and reducing the probability of its progression to gastric cancer.

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ObjectiveBased on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway， this paper explores the effect of Sinisan （SNS） on liver oxidative stress injury in cholestatic hepatitis rats and its mechanism. MethodThirty 6-week-old male SD rats were randomly divided into a control group， model group， low and high dose groups of SNS （2.5 and 5 g·kg-1） and ursodeoxycholic acid group （UDCA， 63 mg·kg-1）， with six rats in each group. Rats were administrated for seven consecutive days. On the 5th day， the control group was given olive oil of 10 mL·kg-1， and the other groups were given alpha-naphthalene isothiocyanate （ANIT） of 80 mg·kg-1. The serum biochemical indicator levels of cholestasis and the content of antioxidant factors in rat liver were detected by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in liver tissue. The relative mRNA and protein expressions of Nrf2， HO-1， and quinone oxidoreductase 1 （NQO1） in liver tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ResultCompared with the control group， the model group showed a significant increase in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）. There were obvious pathological changes in the model group such as the disordered arrangement of hepatocytes， obvious congestion and necrosis in the portal area， infiltration of inflammatory cells， and destruction of the interlobular bile duct. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly down-regulated in the model group （P<0.05， P<0.01）. Compared with the model group， the groups of SNS showed a significant decrease in the serum biochemical indicator levels of cholestasis and the content of antioxidant factors in liver tissue （P<0.01）， and the pathological liver injury was obviously improved. The necrotic area was reduced， and the infiltration of inflammatory cells was decreased. In addition， there was a small amount of extravasated blood in the interlobular vein. The relative mRNA and protein expressions of Nrf2， HO-1， and NQO1 in liver tissue were significantly up-regulated （P<0.05， P<0.01）. ConclusionSNS can significantly improve liver injury in cholestatic hepatitis rats， and its mechanism may be related to the inhibition of oxidative stress response mediated by the Nrf2/HO-1 signaling pathway.

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In terrestrial ecosystems, the nitrogen dynamics, including N2O production, are majorly regulated by a complex consortium of microbes favored by different substrates and environmental conditions. To better predict the daily, seasonal and annual variation in N2O fluxes, it is critical to estimate the temperature sensitivity of different microbial groups for N2O fluxes under oxic and suboxic conditions prevalent in soil and wetlands. Here, we studied the temperature sensitivity of two groups of ammonia oxidizers, archaea (AOA) and bacteria (AOB), in relation to N2O fluxes through both nitrification and nitrifier-denitrification pathways across a wide temperature gradient (10-55 °C). Using square root theory (SQRT) and macromolecular rate theory (MMRT) models, we estimated thermodynamic parameters and cardinal temperatures, including maximum temperature sensitivity (TSmax). The distinction between N2O pathways was facilitated by microbial-specific inhibitors (PTIO and C2H2) and controlled oxygen supply environments (oxic: ambient level; and suboxic: ∼4%). We found that nitrification supported by AOA (NtA) and AOB (NtB) dominated N2O production in an oxic climate, while only AOB-supported nitrifier-denitrification (NDB) majorly contributed (>90%) to suboxic N2O budget. The models predicted significantly higher optimum temperature (Topt) and TSmax for NtA and NDB compared to NtB. Intriguingly, both NtB and NDB exhibited significantly wider temperature ranges than NtA. Altogether, our results suggest that temperature and oxygen supply control the dominance of specific AOA- and AOB-supported N2O pathways in soil and sediments. This emergent understanding can potentially contribute toward novel targeted N2O inhibitors for GHG mitigation under global warming.

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PURPOSE: We constructed a zebrafish xenograft tumor model to compare and quantify the antiangiogenic efficacy and safety of nine vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), axitinib, lenvatinib, pazopanib, apatinib, cabozantinib, sunitinib, semaxanib, sorafenib, and regorafenib, in parallel. METHODS: CT26 and GL261 tumor cells were implanted into the perivitelline space of Tg (flk1: eGFP) zebrafish to construct a xenograft tumor model. VEGFR-TKIs' antiangiogenic efficacy was quantified using AngioTool software, and the median effective dose (ED50) was calculated. The toxicity was evaluated by calculating the median lethal dose (LD50) and gross morphological changes. Cardiac toxicity was further assessed by heart rate, heart rhythm, the distance between the sinus venosus (SV) and bulbus arteriosus (BA), and pericardial edema. RESULTS: Using the zebrafish xenograft tumor model, we found that all nine VEGFR-TKIs exhibited antiangiogenic abilities, but the effectiveness of semaxanib was worse than that of other VEGFR-TKIs. Meanwhile, the zebrafish toxicity assay showed that all tested VEGFR-TKIs were associated with cardiac-related toxicity, especially apatinib and axitinib, which caused serious pericardial edema in zebrafish at relatively low concentrations. A narrow therapeutic window was found for most VEGFR-TKIs, and the simultaneous occurrence of toxic effects of semaxanib was recognized. CONCLUSION: Our findings showed the potential of using a zebrafish xenograft tumor model to accelerate VEGFR-TKI screening and further the development of more efficient and less toxic VEGFR-TKIs.

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Tuberculosis (TB) is an ancient infectious disease. Before the availability of effective drug therapy, it had high morbidity and mortality. In the past 100 years, the discovery of revolutionary anti-TB drugs such as streptomycin, isoniazid, pyrazinamide, ethambutol and rifampicin, along with drug combination treatment, has greatly improved TB control globally. As anti-TB drugs were widely used, multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis emerged due to acquired genetic mutations, and this now presents a major problem for effective treatment. Genes associated with drug resistance have been identified, including katG mutations in isoniazid resistance, rpoB mutations in rifampin resistance, pncA mutations in pyrazinamide resistance, and gyrA mutations in quinolone resistance. The major mechanisms of drug resistance include loss of enzyme activity in prodrug activation, drug target alteration, overexpression of drug target, and overexpression of the efflux pump. During the disease process, Mycobacterium tuberculosis may reside in different microenvironments where it is expose to acidic pH, low oxygen, reactive oxygen species and anti-TB drugs, which can facilitate the development of non-replicating persisters and promote bacterial survival. The mechanisms of persister formation may include toxin-antitoxin (TA) modules, DNA protection and repair, protein degradation such as trans-translation, efflux, and altered metabolism. In recent years, the use of new anti-TB drugs, repurposed drugs, and their drug combinations has greatly improved treatment outcomes in patients with both drug-susceptible TB and MDR/XDR-TB. The importance of developing more effective drugs targeting persisters of Mycobacterium tuberculosis is emphasized. In addition, host-directed therapeutics using both conventional drugs and herbal medicines for more effective TB treatment should also be explored. In this article, we review historical aspects of the research on anti-TB drugs and discuss the current understanding and treatments of drug resistant and persistent tuberculosis to inform future therapeutic development.

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Purpose To explore the application value of ultrasound-guided thyroid fine needle aspiration liquid-based thin layer cytopathology combined with p21 and Cyclin D1 detection in preoperative diagnosis of papillary thyroid carcinoma.Meth-ods Immunocytochemical staining was used to detect the ex-pression differences of p21 and Cyclin D1 between benign and malignant thyroid nodules,and their correlations the clinicopath-ological features.The diagnostic efficacy of US-FNAB,p21,Cyclin D1 and the three combined detection in benign and malig-nant thyroid nodules was evaluated by constructing receiver oper-ating curve.Results The expression of p21 and Cyclin D1 was up-regulated in the papillary thyroid carcinoma group,86.36%(57/66)and 93.94%(62/66),and 1.96%(1/52)and 5.77%(3/52)in the benign nodule group,respectively;the difference between the two groups was significant(P<0.05).The positive rates of p21 and Cyclin D1 in BRAF V600E wild type PTC were 88.89%(8/9).The expression of p21 and Cyc-lin D1 was correlated with the tumor size of PTC(P<0.05),but not with gender,age,number of tumor foci,lymph node metastasis,and TNM stage(P>0.05).The sensitivity,speci-ficity,positive predictive value and negative predictive value of US-FNAB,p21 and Cyclin D1 combined detection were 95.45%,98.07%,98.43%and 94.44%,respectively,which were higher than those of US-FNAB independent detection,and the sensitivity and negative predictive value were higher than those of BRAF V600E.The area under ROC curve of US-FNAB,p21 and Cyclin D1 combined detection(AUC = 0.967 7)was larger than that of US-FNAB(AUC = 0.849 9)and the difference between the two was statistically significant(P<0.05).The area under ROC curve of the combined detection of the three was greater than that of independent detection of BRAF V600E(AUC =0.931 8),and the combined detection of US-FNAB with p21(AUC = 0.946 4)or Cyclin D1(AUC = 0.944 3).It was close to that of US-FNAB combined BRAF V600E detection(AUC = 0.971 2).Conclusion US-FNAB combined with p21 and Cyclin D1 immunohistochemical detec-tion can help improve the sensitivity of preoperative diagnosis of papillary thyroid carcinoma,and it has high diagnostic value for BRAF V600E wild-type papillary carcinoma.

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Objective:To investigate the prevalence of metabolic syndrome(MS) among adult residents with different characteristics and the relationship between serum uric acid(SUA) level and MS using the data of Chinese Adult Chronic Diseases and Nutrition Surveillance(2018) program in Anhui.Methods:Multi-stage stratified cluster random sampling was used to select participants aged 18 and over for questionnaires, physical measurements, and laboratory tests. The complex weighted method was used to estimate the prevalence of MS among residents with different characteristics. Logistic regression model based on complex sampling data was used to analyze the relationship between SUA and MS. Receiver operating characteristic(ROC) curve was used to evaluate the reliability of SUA in diagnosing MS and determine the optimal cutoff point.Results:A total of 7 182 participants were included and the prevalence of MS among adult residents was 29.46%. The prevalence of MS was higher in females(33.76%) than that in males(25.28%), and the difference was statistically significant( P<0.05). After adjusting for other factors, for every 10 μmol/L increase in SUA, the risk of MS increased by 4% in males( OR=1.040, 95% CI 1.019-1.061) and 7% in females( OR=1.070, 95% CI 1.059-1.082). The area under the curve(AUC) for SUA in diagnosing MS was 0.816(95% CI 0.806-0.826), with a sensitivity of 0.761 and specificity of 0.727. The optimal cutoff point for SUA was 450 μmol/L. Conclusion:The prevalence of MS among adult residents in Anhui Province is 29.46%. SUA is a risk factor for MS, and increasing SUA level indicated a higher risk of MS. The optimal cutoff value of SUA may be helpful in diagnosing MS.

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Objective:To observe alterations of macular outer retinal reflectivity (ORR) and the associations with macular vessel density in patients with nonproliferative diabetic retinopathy (NPDR).Methods:A retrospective cross-sectional study. From August 2021 to March 2022, a total of 63 NPDR patients with 63 eyes (NPDR group) diagnosed by Department of Ophthalmology of Guangdong Provincial People'sHospital were included in the study. There were 39 males with 39 eyes and 24 females with 24 eyes. Age was 60 (52, 68) years. A total of 66 eyes of 66 healthy volunteers matching age and sex were selected as the control group. Among them, 40 men had 40 eyes and 26 women had 26 eyes. Age was 58 (52, 67) years. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed in all affected eyes. Image J software was used to calculate ORR, including the optical density of ellipsoid zone (EZ), photoreceptor outer segment (OS), photoreceptor inner segment (IS) and outer nuclear layer (ONL) by OCT examination. The sampling sites were horizontal and vertical scanning of the fovea of the macula on 500 μm (nasal 500, temporal 500, superior 500, inferior 500), 1 000 μm (nasal 1 000, temporal 1 000, superior 1 000, inferior 1 000) and 2 000 μm (nasal 2 000, temporal 2 000, superior 2 000, inferior 2 000). The software automatically divided the retina within 6 mm of the macular fovea into the fovea with a diameter of 1 mm, the parafovea with a diameter of 1-3 mm, and the perifovea with a diameter of 3-6 mm by macular OCTA examination. The blood density of superficial capillary plexus and deep capillary plexus in different zones in the macular area were measured by the built-in software of the device. Spearman correlation analysis was used to analyze the correlation between ORR and blood flow density. Results:Compared with the control group, retinal reflectivity of EZ in NPDR group was significantly decreased at other sites except the fovea, retinal reflectivity of OS was significantly decreased at nasal 2 000, temporal 2 000, superior 2 000 and superior 1 000; retinal reflectivity of IS was significantly decreased at superior 1 000, superior 500 and inferior 500. The retinal reflectivity of ONL in macular fovea was significantly decreased, and the differences were statistically significant ( P<0.05). The ORR was positively correlated with blood flow density, and the correlation coefficient in NPDR group was lower than that in control group. The results of multifactor linear regression analysis showed that the superior and temporal ORR were correlated with blood flow density ( P<0.05). Conclusions:Compared with the control group, ORR is reduced and less correlated with vessel density in NPDR patients. ORR is more affected by retinal blood flow density in temporal and superior parts.

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Professor JIAO Mian-zhai 's academic characteristics and needling essentials in acupuncture field are introduced in the paper. Professor JIAO integrated martial arts and qigong with acupuncture needling technique, and then created his own "yunzhang bafa" (eight kinds of palm movement and qi training method) and modified the basic skills for finger strength practice and needling techniques. On the base of the needling techniques exerted by both hands, he developed a set of "JIAO 's needling techniques", including the manipulations of needle insertion and withdrawal. He proposed that the compound needling techniques for reinforcing and reducing should be cooperated with the physician's respiratory rhythm. Besides, he clarified the operation timing of reinforcing and reducing techniques to ensure the full play to the curative effect of acupuncture.

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Diabetic macular edema (DME) is the main cause of vision loss and even blindness in patients with diabetic retinopathy. Intravitreal anti-vascular endothelial factor therapy has become the gold standard management of DME. However, not all eyes response optimally to common management of DME, which could be due to the differences of individual factors. Increasing age could be the predictive factors for poor outcome. The influence of glycemic control, hypertension, dyslipidemia, chronic kidney disease and relative factors on treatment response require further investigation. Identifying the systemic factors that influence the treatment response of DME can provide the evidence to predict the prognosis of DME, and improve the efficacy of clinical treatment.

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Autophagy is a programmed cell degradation process that is involved in a variety of physiological and pathological processes including malignant tumors. Abnormal induction of autophagy plays a key role in the development of hepatocellular carcinoma (HCC). We established a prognosis prediction model for hepatocellular carcinoma based on autophagy related genes. Two hundred and four differentially expressed autophagy related genes and basic information and clinical characteristics of 377 registered hepatocellular carcinoma patients were retrieved from the cancer genome atlas database. Cox risk regression analysis was used to identify autophagy-related genes associated with survival, and a prognostic model was constructed based on this. A total of 64 differentially expressed autophagy related genes were identified in hepatocellular carcinoma patients. Five risk factors related to the prognosis of hepatocellular carcinoma patients were determined by univariate and multivariate Cox regression analysis, including TMEM74, BIRC5, SQSTM1, CAPN10 and HSPB8. Age, gender, tumor grade and stage, and risk score were included as variables in multivariate Cox regression analysis. The results showed that risk score was an independent prognostic risk factor for patients with hepatocellular carcinoma ( HR = 1.475, 95% CI = 1.280-1.699, P < 0.001). In addition, the area under the curve of the prognostic risk model was 0.739, indicating that the model had a high accuracy in predicting the prognosis of hepatocellular carcinoma. The results suggest that the new prognostic risk model for hepatocellular carcinoma, established by combining the molecular characteristics and clinical parameters of patients, can effectively predict the prognosis of patients.

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Understanding the environmental niche segregation of ammonia-oxidizing archaea (AOA) and bacteria (AOB) and its impact on their relative contributions to nitrification and nitrous oxide (N2O) production is essential for predicting N2O dynamics within an ecosystem. Here, we used ammonia oxidizer-specific inhibitors to measure the differential contributions of AOA and AOB to potential ammonia oxidization (PAO) and N2O fluxes over pH (4.0-9.0) and temperature (10-45 °C) gradients in five soils and three wetland sediments. AOA and AOB activities were differentiated using PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide), 1-octyne, and acetylene. We used square root growth (SQRT) and macromolecular rate theory (MMRT) models to estimate cardinal temperatures and thermodynamic characteristics for AOA- and AOB-dominated PAO and N2O fluxes. We found that AOA and AOB occupied different niches for PAO, and soil temperature was the major determinant of niche specialization. SQRT and MMRT models predicted a higher optimum temperature for AOA-dominated PAO and N2O fluxes compared with those of AOB. Additionally, PAO was dominated by AOA in acidic conditions, whereas both AOA- and AOB-dominated N2O fluxes decreased with increasing pH. Consequently, net N2O fluxes (AOA and AOB) under acidic conditions were approximately one to three-fold higher than those observed in alkaline conditions. Moreover, structural equation and linear regression modeling confirmed a significant positive correlation (R2 = 0.45, p < 0.01) between PAO and N2O fluxes. Collectively, these results show the influence of ammonia oxidizer responses to temperature and pH on nitrification-driven N2O fluxes, highlighting the potential for mitigating N2O emissions via pH manipulation.

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This study is aimed to comprehend the treatment of non-submerged attached growth systems using bio-sponge, bio-cord, and bio-cloth media. Three reactors were set up with internal recirculation ratio of 1 (IR = 1) and similar media surface area. Bio-sponge and bio-cloth reactors showed removal of COD (79 vs. 76%) and NH4+-N (78 vs. 73%). While bio-cord treatment was deteriorated due to time-dependent process. Multiple linear regression revealed that alkalinity governed the formation degree of the anaerobic zone in bio-sponges, partially affecting nitrification. Increasing IR from 1 to 3 caused sloughing of the attached biomass and was positively correlated with effluent nitrite nitrogen concentration, indicating the sensitivity of nitrification to spatial distribution effects. In addition, bio-sponge system obtained superior performance at IR of 2 while bio-cloth one might be also an effective media for wastewater treatment if having good durability.

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Objective:To analyze the distribution characteristics of peripheral retinopathy in Chinese patients with diabetic retinopathy (DR).Methods:A cross-sectional study. From January to December 2019, 265 cases of 388 eyes of DR patients diagnosed in the eye examination of Guangdong Provincial People's Hospital were included in the study. Among them, there were 211 eyes in 148 males and 177 eyes in 117 females; the average age was 58.4±12.3 years. Ultra-wide-angle fundus imaging (UWF) examination was performed by Daytona in Aalborg, UK. Use Photoshop to simulate the standard 7-azimuth (S7F) area, which was used as the central retinal area 1-7. The peripheral retinal areas 3-7 (P3-P7) were the adjacent peripheral retinal areas of the central retinal area 3-7, respectively. Divided DR into peripheral lesion predominant type (PPL) and central lesion predominant type (PCL). PPL was defined as at least one peripheral retinal area with more severe disease than its adjacent central area. χ 2 test was performed on the difference of PPL composition ratio in each retinal area of eyes with different DR stages. Results:Among 388 eyes, 200 eyes were PPL (51.5%, 200/388). Compared of PPL composition ratios of eyes with different stages of DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR were 32 (36.8%, 32/87), 89 (55.3%, 89/161)), 42 (51.9%, 42/81), 37 (62.6%, 37/59), the difference was statistically significant ( χ2=11.440, P=0.010). Comparison of the distribution of PPL in each retinal area in DR eyes: in 200 PPL eyes, areas 3, 4, 5, 6, and 7 have 87, 101, 78, 67, and 38 eyes, respectively. The distribution of PPL in each retinal area in DR eyes was compared, and the difference was statistically significant ( χ2=37.640, P<0.001). Conclusions:PPL accounts for 51.5% of the eyes with DR. The DR stage are more severe, the proportion of PPL is higher. The temporal retinal peripheral lesions are the most common.

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OBJECTIVE@#To investigate the mechanism of Radix Kansui (RK) stir-fried with vinegar (VRK) decreased hepatotoxicity in mice.@*METHODS@#According to a random number table, 40 mice were randomly divided into negative control group (0.5% carboxymethylcellulose sodium, 20 mL/kg), positive control group (0.1% mixture of carbon tetrachloride in soybean oil, 20 mL/kg), RK group (the ethyl acetate extracts of RK, 250 g crude drug/kg) and VRK group (the ethyl acetate extracts of VRK, 250 g crude drug/kg) with 10 mice per group. All mice were administered orally by gavage daily for 7 continuous days. The morphology of liver tissues was examined to assess the liver injury by a transmission electron microscope. Hepatocyte apoptosis in vivo was determined by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nickend labeling (TUNEL) assay. Immunohistochemical technique was adopted to detect the expression of particular antiapoptotic and proapoptotic proteins in the mitochondrial pathways, including B-cell lymphoma (Bcl-2) and caspase-3, as well as the expression of inflammatory mediators, including nuclear factor kappa B (NF- κ B) and intercellular adhesion molecule-1 (ICAM-1).@*RESULTS@#Liver injury and hepatocyte apoptosis were observed in RK mice, and the liver injury were significantly reduced in VRK-treated mice. In immunohistochemistry study, compared with the negative control group, RK inhibited dramatically the Bcl-2 protein expression and significantly increased the expression of caspase-3, NF- κ B and ICAM-1 (all P<0.01). Compared with the RK group, VRK group induced significant increase on Bcl-2 protein expression, and decreased the caspase-3, NF- κ B and ICAM-1 protein expression (P<0.05 or P<0.01).@*CONCLUSION@#The mechanism of reduced hepatotoxicity of VRK may be associated with the reduced inflammation, regulation of antiapoptotic and proapoptotic mediators in the mitochondrial pathway.

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Multi-template molecularly imprinted solid phase extraction not only has the advantages of high selectivity, large adsorption capacity, easy preparation, reuse and low environmental pollution, but also can realize the enrichment and separation of many kinds of compounds. It has attracted wide attention in the extraction and separation of traditional Chinese medicine components. This study summarizes the latest development of multi-template molecularly imprinted solid phase extraction. At the same time, based on the classification of active components of traditional Chinese medicine (flavonoids, alkaloids, phenylpropanol, terpenes, etc.), the latest application of multi-template molecular imprinting solid phase extraction in multi-component separation of traditional Chinese medicine was reviewed, with a view to better application of multi-template molecularly imprinted polymer in active multi-component extraction and separation of traditional Chinese medicine and provide reference for the material basic research of the efficacy of traditional Chinese medicine.

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To investigate the transnasal absorption characteristics of Cistanche deserticola phenylethanol glycosides nanoemulsion and its influencing factors. With the use of the classic in vivo nasal circulation perfusion model in rats, the absorption rate constant was used as the index to compare the nasal absorption characteristics of C. deserticola phenylethanol glycosides nanoemulsion and its aqueous solution in different concentrations, and to explore the effects of pH value of the preparation and absorption accelerator Azone on the nasal absorption of C. deserticola phenylethanol glycosides nanoemulsion. The results showed that, as compared with the aqueous solution group, the absorption rate constant was significantly higher in C. deserticola phenylethanol glycosides nanoemulsion with the same concentration(P<0.05), and C. deserticola phenylethanol glycosides nanoemulsion was more easily absorbed by the nasal cavity of rats; with the increase of the concentration of C. deserticola phenylethanol glycosides, the transnasal absorption amount of nanoemulsion was also increased in a dose-dependent manner. When the pH value of nanoemulsion was 6.0 and the ratio of Azone was 2%, the absorption rate constant was highest and the effect of promoting infiltration was the best.

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SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease has been implicated in virus maturation, dysregulation of host inflammation and antiviral immune responses. We showed that PLpro preferably cleaves the K48-ubiquitin linkage while also being capable of cleaving ISG15 modification. The multiple functions of PLpro render it a promising drug target. Therefore, we screened an FDA-approved drug library and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising IC50 of 2.1 M. The co-crystal structure of SARS-CoV-2 PLpro-C111S in complex with GRL0617 suggests that GRL0617 is a non-covalent inhibitor. NMR data indicate that GRL0617 blocks the binding of ISG15 to PLpro. The antiviral activity of GRL0617 reveal that PLpro is a promising drug target for therapeutically treating COVID-19. One Sentence SummaryCo-crystal structure of PLpro in complex with GRL0617 reveals the druggability of PLpro for SARS-CoV-2 treatment.

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OBJECTIVE: To reflect the changes of medicine price level in China after canceling the maximum retail price limit, and to provide reference for the improvement of medicine price policy. METHODS: This research utilizes data of Chinese medicine economic information database of Chinese Pharmaceutical Association from January 2015 to March 2019 and compiles comprehensive and classified chained fisher price indexes among diverse policy control levels and different treatment categories. RESULTS: Over the past four years, the sale of west medicine(WM) by Chinese medical institutions showed a trend of decreasing price, with a decline of 13.99%. And the price of traditional Chinese medicine (TCM) showed a trend of first rising and then falling, with a decline of 3.54%. From the analysis on different policy control levels, the price of medical insurance WM, non-medical insurance WM, medical insurance TCM and non-medical insurance TCM decreased by 13.32%, 14.27%, 1.36% and 14.29%, respectively. The price of medical insurance TCM fell less. And the price of non-medical insurance TCM rose and fell too quickly in a short period of time, and its fluctuation was obvious. Among medical insurance medicines, the price of category A WM raised by 4.5%, while the prices of category B WM, category A TCM and category B TCM dropped by 15.90%, 0.66% and 1.47%, respectively. The price of essential WM, non-essential WM, essential TCM and non-essential TCM reduced by 13.72%, 13.90%, 3.70% and 3.60%, respectively. From the analysis on different treatment categories, the prices of diabetes medicines, hypertension medicines and systemic anti-infection medicines decreased by 6.78%, 10.42% and 12.72%, respectively. Anticancer medicines had largest price decline with 26.69%. CONCLUSION: After canceling the maximum retail price limit, the price of WM declines steadily, while the price of TCM first rises and then falls. The changes of medicine prices vary greatly at different policy control levels. The trends of medicine price reduction among different treatment categories are the same, but the differences are large.