Establishment of Poly （I∶C）-induced Cytokine Storm Model in Mice and Intervention Effect of Artesunate and Qingfei Paidu Decoction / 中国实验方剂学杂志

ObjectiveTo observe the intervention effect of artesunate （ART） and Qingfei Paidu decoction （QFPD） on the mouse model of cytokine storm （CS） induced by viral mimic Poly （I∶C）. MethodEighty-four SPF male BALB/c mice were randomly divided into seven groups， with 12 mice in each group. Mice， except for those in the blank group （n=12）， were subjected to CS model induction by tail vein injection of Poly （I∶C） at 15 mg·kg-1， followed by drug treatments of low-dose ART （ART-l， 10 mg·kg-1）， medium-dose ART （ART-m， 20 mg·kg-1）， high-dose ART （ART-h， 40 mg·kg-1）， Qingfei Paidu Decoction （QFPD， 2.4 g·kg-1）， and dexamethasone （DXM， 10 mg·kg-1）. After 6 hours， lung tissues， bronchoalveolar lavage fluid （BALF）， spleen， lung， and peripheral blood were collected. The lung and spleen indexes were calculated and the number of inflammatory cells in BALF was detected. The pathological changes in lung tissues were observed by hematoxylin-eosin （HE） staining and the levels of tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， and IL-6 in BALF were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of immune cells in BALF and peripheral blood was detected by flow cytometry. ResultThe analysis of lung and spleen indexes showed that compared with the blank group， the model group showed increased lung and spleen indexes to varying degrees （P<0.05）. Compared with the model group， the ART groups showed reduced spleen index （P<0.05） and the ART-l group showed reduced lung index （P<0.05）. Additionally， the QFPD group showed reduced lung and spleen indexes （P<0.05）. ELISA results showed that except for TNF-α， the levels of IFN-γ， IL-1β， and IL-6 in the model group increased compared with those in the blank group （P<0.05）. Compared with the model group， the ART-l group and the QFPD group showed reduced content of TNF-α （P<0.05）， and all groups with drug intervention showed reduced content of IFN-γ， IL-1β， and IL-6 （P<0.05）. The number of inflammatory cells in BALF showed a downward trend in the model group， and the number of cells increased in the groups with drug intervention except for the DXM group （P<0.05）. Flow cytometry showed that compared with the blank group， the model group showed decreased number of CD3 in the peripheral blood （P<0.05）， increased Ly-6G and F4/80 （P<0.05）， decreased expression of CD45， CD3， and F4/80 in BALF （P<0.05）， and increased expressions of Ly-6G （P<0.05）. Compared with the model group， the ART groups and QFPD group showed increased CD45 content in peripheral blood （P<0.05）， decreased Ly-6G and F4/80 content （P<0.05）， increased CD45 and F4/80 content in BALF （P<0.05）， and decreased expression of Ly-6G （P<0.05）. ConclusionART and QFPD have a good protective effect on Poly （I∶C）-induced CS in mice， and the mechanism is related to the effective intervention in immune cell disorder.

Acupuncture for glaucoma-induced optic atrophy: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture for glaucoma-induced optic atrophy.@*METHODS@#A total of 70 patients (89 affected eyes) with glaucoma-induced optic atrophy were randomized into an observation group and a control group, 35 cases in each group. The control group was given basic western medicine treatment. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at main acupoints i.e. Baihui (GV 20), Shangjingming (Extra), Chengqi (ST 1), Fengchi (GB 20), Zusanli (ST 36), combined with supplementary acupoints based on syndrome differentiation, once every three days, twice a week. The treatment for 3 months was required in both groups. Before treatment, after treatment and in follow-up of 6 months after treatment, the best corrected visual acuity (BCVA), intraocular pressure (IOP), indexes of visual field (visual field index [VFI], mean deviation [MD], pattern standard deviation [PSD]) and mean thickness of retinal nerve fiber layer (RNFL) were observed in the two groups.@*RESULTS@#Compared before treatment, BCVA was decreased after treatment and in follow-up in the control group (P<0.05); in the follow-up, BCVA in the observation group was higher than that in the control group (P<0.05). On each time point before and after treatment, there was no significant difference within or between the two groups (P>0.05). After treatment and in the follow-up, the mean thickness of RNFL was larger than the control group (P<0.05).@*CONCLUSION@#On the basis of the basic western medicine treatment, acupuncture can delay the decline of vision and the thinning of retinal nerve fiber layer in patients with glaucoma-induced optic atrophy.

The effect of age and abstinence time on semen quality: a retrospective study / 亚洲男科学杂志(英文版)

This study analyzed the effects of male age and abstinence time on semen quality and explored the best abstinence time for Chinese males among different age groups. Semen parameters, including sperm kinetics, morphology, and DNA fragmentation index (DFI), were reviewed from 2952 men. Samples were divided into six age groups (≤25 years, 26-30 years, 31-35 years, 36-40 years, 41-45 years, and >45 years) and were divided into six groups according to different abstinence time (2 days, 3 days, 4 days, 5 days, 6 days, and 7 days). The differences in semen quality between the groups were compared, and the effect of age and abstinence time on semen quality was analyzed. Significant differences were observed in semen volume, progressive motility (PR), and DFI among the age groups (all P < 0.05), and no significant differences were observed in sperm morphological parameters (all P > 0.05). There were significant differences in semen volume, PR, and DFI among different abstinence time groups (all P < 0.05) and no significant differences in sperm morphological parameters (all P > 0.05). Pearson analysis showed that male age and abstinence time were both significantly correlated with sperm kinetics and DFI (both P < 0.05), while no significant correlation was found with sperm morphological parameters (all P > 0.05). The box plots and histograms of men's age, abstinence time, and semen quality show that most semen quality parameters differ significantly between the 2 days and 7 days abstinence groups and other groups at different ages. Except for the sperm morphology parameters, sperm kinetic parameters and sperm DFI are linearly related to male age and abstinence time.

Resistance of C57BL/6 Mice to Different Artemisinin-sensitive Strains of PbK173 / 中国实验方剂学杂志

ObjectiveThe tolerance of C57BL/6 mice to artemisinin-sensitive and -resistant strains of Plasmodium berghei （Pb） K173 and the differences in blood parameters， spleen coefficient and spleen structure during infection were compared to explore whether the artemisinin resistance of Pb would aggravate malaria infection. MethodPbK173 artemisinin-sensitive and -resistant strains were tested in parallel. C57BL/6 mice were randomly divided into 1 control group， 4 artemisinin-sensitive strain groups and 4 artemisinin-resistant strain groups by body weight. Each infection group was simultaneously inoculated （ip） with 1×107 infected red blood cells （iRBCs） of sensitive/resistant strain. For the mice in the survival test group， the body weight was recorded every day post infection， and the tail vein blood smear was collected to calculate the Pb infection rate. In the other infection groups， peripheral blood and spleen were collected on 2， 5 and 9 d after infection. Peripheral blood parameters， spleen coefficient， pathological section of spleen and spleen cells were detected in each group. ResultOn 1-3 d after infection， the infection rate of the resistant strain （0.4±0.0， 0.8±0.1， 1.9±0.4）% was always higher than that of the sensitive strain （0.2±0.1， 0.4±0.1， 1.1±0.3）% （P<0.01）. From the 4th d of infection， the infection rate of the two groups gradually approached. The survival period of the sensitive strain group （20.5±1.2） d was shorter than that of the resistant strain group （23.3±1.4） d （P<0.01）. On the 9th d， the white blood cell count of the sensitive strain group （16.2±1.1）×109 cells/L was higher than that of the resistant strain group （10.6±1.8）×109 cells/L （P<0.01）. Flow cytometry analysis of spleen cells showed that the sensitive strain group （3.6±0.4） demonstrated a higher CD4+/CD8+ value than the resistant strain group （2.3±0.2） on the 9th d （P<0.01）. The spleen of C57BL/6 infected mice was gradually enlarged during infection， and on the 9th d， the resistant strain group （3.1±0.1）% showed a higher spleen coefficient than the sensitive strain group （2.7±0.2）% （P<0.01）. In the early stage of C57BL/6 infected mice， the red pulp of spleen was hyperemic and swollen. On the 9th d， the marginal area of the spleen disappeared and the structure of the red and white pulp was destroyed. ConclusionWithout drug treatment， the protective immune responses of peripheral blood and spleen of C57BL/6 mice were more sensitive to PbK173 artemisinin-sensitive strain. The artemisinin-resistant strain of PbK173 bred with mouse-to-mouse blood transmission and increased artemisinin dose exhibited shortened growth period and reduced toxicity.

Effect of Dihydroartemisinin on Oxidative Damage and Energy Metabolism of HepG2 Cells and Its Synergistic Effect with Sorafenib / 中国实验方剂学杂志

Objective:To explore the inhibitory effect of dihydroartemisinin （DHA） on the proliferation of HepG2 cells， elucidate the mechanism from the perspectives of oxidative damage and energy metabolism， and discuss the possibility of combined use of DHA with sorafenib （Sora）. Method:Cell counting kit-8 （CCK-8） assay was used to obtain the 50% inhibitory concentration （IC₅₀） of DHA and Sora on HepG2 and SW480 cells and Chou-Talalay method was used to obtain the combination index （CI） of DHA and Sora. HepG2 cells were classified into the control group， DHA group （10 µmol·L^-1）， Sora group （5 µmol·L^-1）， and DHA + Sora group （DHA 10 µmol·L^-1， Sora 5 µmol·L^-1） and then incubated with corresponding drugs for 8-12 h. Seahorse XF glycolytic rate assay kit and cell mito stress test kit were employed to respectively detect the glycolysis function of cells and oxidative phosphorylation function of mitochondria. DCFH-DA and lipid peroxidation MDA assay kit were separately used to analyze the intracellular levels of reactive oxygen species （ROS） and malondialdehyde （MDA）. Western blot was applied to determine the intracellular levels of heme oxygenase-1 （HO-1） and glutamate-cysteine ligase catalytic subunit （GCLC）. Result:Compared with the control group， DHA alone inhibited the ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， increased the levels of intracellular ROS and MDA （<italic>P<</italic>0.05）， and decreased the levels of HO-1 and GCLC （<italic>P<</italic>0.05） in HepG2 cells. DHA and Sora had synergistic inhibitory effect on proliferation of HepG2 and SW480 cells， with CI < 0.90. The DHA + Sora group showed stronger suppression of ATP synthesis in mitochondrial oxidative phosphorylation and glycolysis （<italic>P</italic><0.01）， higher levels of intracellular ROS and MDA （<italic>P<</italic>0.01）， and lower levels of intracellular antioxidation-related proteins HO-1 and GCLC in HepG2 cells （<italic>P<</italic>0.01） than the DHA group. Conclusion:DHA may increase the level of MDA by reducing HO-1 and GCLC and increasing ROS in HepG2 cells， which results in mitochondria oxidative damage， restricts cell glycolysis and mitochondrial oxidative phosphorylation， and thus finally inhibits the proliferation of HepG2 cells. DHA and Sora have synergistic inhibitory effect on the proliferation of HepG2 and SW480 cells， and the mechanism may be related to the synergistic oxidative damage that affects the mitochondrial electron transport chain and suppresses cell energy metabolism.

Effects of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes complicating hypertension: a meta-analysis / 中华心血管病杂志

Objective: To analyze the effects of different types of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on 24-hour ambulatory blood pressure in patients with type 2 diabetes mellitus and hypertension. Method: In this meta-analysis, we searched for randomized controlled trials on the effect of SGLT2i on 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension. Three databases, namely PubMed, Web of Science and Cochrane Library, were searched. The search was organized on the concept of 3 conceptual groups: the first group contained terms used to describe SGLT2i, the second group contained terms related to blood pressure, and the third group contained terms used to describe randomized controlled trials. The search time was from the establishment of the database to December 2020. The inclusion and exclusion criteria were formulated in accordance with the requirements of the Cochrane systematic review. According to whether the heterogeneity of the study was significant or not, a random effect model or a fixed effect model were used to conduct the analysis on the impact of different types of SGLT2i on 24-hour ambulatory blood pressure and day and night blood pressure in patients with type 2 diabetes and hypertension. Further subgroup analysis was performed to define potential factors, which might lead to clinical heterogeneity. Results: Seven clinical trials were finally included. The result of the meta-analysis showed that compared with placebo group, SGLT2i could reduce the 24-hour dynamic systolic blood pressure of patients with type 2 diabetes and hypertension by 4.36 mmHg (1 mmHg=0.133 kPa). Reduction was 4.59, 3.74, 5.06, and 3.64 mmHg by canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin respectively; SGLT2i could reduce the 24-hour dynamic diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.20 mmHg, and the reduction was 2.30, 1.22, 2.00, and 2.69 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin respectively. SGLT2i could reduce the daytime systolic blood pressure of patients with type 2 diabetes and hypertension by 5.25 mmHg, and reduction was 5.38, 4.87, 6.00, and 4.37 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. Simultaneously, SGLT2i could reduce the diastolic blood pressure of patients with type 2 diabetes and hypertension by 2.62 mmHg, and the reduction was 2.56, 2.47, and 2.80 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. SGLT2i could reduce the nighttime systolic blood pressure of patients with type 2 diabetes and hypertension by 3.62 mmHg, and the reduction was 2.09, 2.06, 3.92, and 2.45 mmHg by canagliflozin, dapagliflozin, empagliflozin and ertugliflozin, respectively. At the same time, SGLT2i could reduce the nighttime diastolic blood pressure of patients with type 2 diabetes and hypertension by 1.60 and 1.51 mmHg, the reduction was 1.53 and 2.58 mmHg by canagliflozin, empagliflozin and ertugliflozin, respectively. Conclusion: SGLT2i can reduce 24-hour ambulatory blood pressure in patients with type 2 diabetes and hypertension.

Treatment of intra-articular calcaneal fractures with precise screw placement into sustentaculum tali based on virtual and simulation techniques / 中华创伤骨科杂志

Objective:To evaluate the clinical application of virtual and simulation techniques to aid pre-operative design for precise screw placement into the sustentaculum tali in the treatment of intra-articular calcaneal fractures.Methods:From January 2016 to January 2019, 68 patients were treated at Department of Orthopaedics, Suqian Hospital Affiliated to Xuzhou Medical University for intra-articular calcaneal fractures of Sanders types Ⅱ-Ⅳ. According to different designs of screw placement into the sustentaculum tali, they were assigned into a control group (38 cases and 42 feet) and an observation group (30 cases and 33 feet). There were 24 males and 14 females with an age of 39.3 years±8.8 years in the control group. There were 17 males and 13 females with an age of 42.0 years ± 7.6 years in the observation group. The control group was given a routine placement design based on the X-ray and MSCT scanning images of the injured feet. In the observation group, a Mimics model was first constructed using the X-ray and MSCT scanning images of the normal or less injured feet for further virtual screw placement into the sustentaculum tali on a 3D printed model. The disparity was investigated between the parameters designed and the actual values in both groups. The 2 groups were compared in terms of average placements, screw distribution, placement accuracy, placement time and Maryland scores of foot function one year after operation.Results:There were no significant differences in the preoperative general data between the 2 groups, showing comparability ( P>0.05). The design parameters and actual values in the control group were respectively as follows: 17.7°±3.2° versus 15.1°±5.9° in upward oblique angle, 20.3°±2.1° versus 16.2°±6.8° in backward oblique angle, and 47.9 mm ± 3.8 mm versus 45.4 mm ± 4.2 mm in length of screw path, showing significant differences ( P< 0.05). The design parameters and actual values in the observation group were as follows: 16.5°±3.5° versus 17.1°±3.9° in upward oblique angle, 20.9°±4.3° and 19.6°±3.8° in backward oblique angle, and 48.1 mm ± 3.1 mm versus 47.3 mm ± 3.8 mm in length of screw path, showing insignificant differences ( P>0.05). The average screw placements into the sustenta culum tali in the observation group (1.6±0.5) were significantly more than those in the control group (1.2±0.4). Compared with the control group, the observation group had a higher rate of placement of 2 screws[60.6 % (20/23) versus 16.7% (7/42)], higher accuracy of placement [94.3% (50/53) versus 77.6% (38/49)], less placement time for each screw (9.6 mm±3.9 min versus 13.2 mm±4.7 mm), less placement time for each foot (15.6 mm±4.8 min versus 20.5 mm±3.8 mm), and higher Maryland scores at one year after operation (94.2±6.5 versus 89.7±6.9). All the above comparisons were statistically significant ( P<0.05). Conclusions:Application of virtual and simulation techniques to aid pre-operative design for precise screw placement into the sustentaculum tali can improve the outcomes of intra-articular calcaneal fractures, because it increases the number of screws placed, enhances quality of screw placement, shortens operation time, and thus facilitates functional recovery of the injured foot.

Role of gut microbiota in chronic liver disease and its potential therapeutic strategies / 中国药理学通报

An increasing number of studies have shown that intestinal microbes play an important role in maintaining liver homeostasis. The liver is closely linked to the intestine through the portal vein, and the transfer of intestinal microbcs, and their metabolites to the liver can affect the normal physiological function of the liver. Willi the deepening of research on intestinal microbes in recent years, a large number of studies have found that intestinal microbes play an important role in the development of chronic liver diseases. and more and more studies have shown that the regulation of intestinal microbes may be a potential therapeutic target for chronic liver diseases. This article summarizes the role of intestinal microbes in the development of chronic liver diseases and its related mechanisms in recent years, aiming to provide a reference for the prevention and treat-ment of chronic liver diseases.

Synthesis and anti-inflammatory activity of novel isobutyl benzophenone derivatives / 药学学报

Twenty target compounds were synthesized by the reduction reaction of HUANG Minglong and Friedel-Crafts acylation reaction in this study. The inhibitory effects of the new compounds were tested on NO production in LPS-induced mouse macrophage RAW264.7 cells, a cellular inflammation model. The structure-activity relationships were discussed. The structures of target compounds were confirmed by ESI-MS, 1H NMR and 13C NMR. In vitro activity experiments showed that 18 compounds had certain anti-inflammatory effects at the concentration of 40 μmol·L-1, of which 9a, 8b, 7c and 9c showed strong anti-inflammatory activities, and IC50 of 7c and 9c were comparable to the positive control drug ibuprofen.

A comparative split-face study of intense pulsed light versus 595-nm pulsed dye laser in the treatment of post-acne erythema / 中华皮肤科杂志

Objective To evaluate and compare the clinical efficacy and safety of intense pulsed light (IPL) versus 595-nm pulsed dye laser (PDL) for the treatment of post-acne erythema.Methods A randomized split-face clinical trial was conducted.A total of 20 patients with post-acne erythema were enrolled,and randomized to receive treatment with IPL on one half of the face and 595-nm PDL on the other facial side once every 4 weeks for 3 sessions.Digital photographs were taken using the VISIA,and erythema index was recorded before each treatment and one month after the last treatment.The severity of bilateral facial erythema was evaluated based on a 4-point grading scale before the first treatment and after the last treatment.Pain scores and adverse reactions were recorded using a visual analogue scale (VAS) after each treatment,and a patient satisfaction survey was conducted by questionnaire at the last follow-up.Results The mean erythema index on the IPL side before and after treatment was 472.25 ± 86.02 and 357.15 ±82.71 respectively,and that on the PDL side before and after treatment was 476.40 ± 74.25 and 360.05 ± 64.83 respectively.Repeated measures analysis of variance (ANOVA) showed that the erythema indices on both treated sides significantly decreased over time (F =197.666,P ＜ 0.001),and the efficacy of IPL was better than that of PDL (F =1 173.909,P ＜ 0.001).Erythema severity grades on the IPL side as well as on the PDL side significantly differed between before and after treatment (Z =28.735,31.450,respectively,both P ＜ 0.001).As VAS showed,the pain score on the PDL side was significantly lower than that on the IPL side (t =2.468,P ＜ 0.05).Among the 20 patients,17 and 15 assessed their improvement as good or excellent after PDL and IPL treatment respectively,but there was no significant difference between the two groups (Z =2.696,P ＞ 0.05).The adverse reactions included erythema,burning sensation,tense sensation,blistering and hyperpigmentation on IPL-treated side,and erythema and purpuric reactions on the PDL-treated side,which all disappeared in a few hours to several days.Conclusions Both IPL and 595-nm PDL are effective and safe for the treatment of post-acne erythema,and are worthy of clinical promotion and application.IPL shows superiority in the efficacy,but elicits higher pain sensation compared with PDL.

Longniu Bugu Decoction for prevention and treatment of bone loss caused by endocrine therapy of premenopausal breast cancer / 中华内分泌外科杂志

Objective To study the clinical effect of Longniu Bubi Granule on prevention and treatment of bone loss caused by premenopausal ovarian function suppression (OFS) combined with breast cancer aromatase inhibitor (AIs).Methods Forty patients with postmenopausal and high risk of breast cancer treated with OFS combined with aromatase inhibitors were divided into treatment group (n=23) and control group (n=17).The two groups were treated with calcium VitD3125IU,1 tablet per day.The treatment group received the additional of Longniu Bugu Decoction,2 doses daily,with continuous medication for 6 months.The bone mineral density (BMD) level,bone mineral density (T) and serum bone alkaline phosphatase (BALP) were measured before and 6 months after treatment.Results There were significant differences in lumbar (L2-4) and femoral neck bone mineral density,bone mineral density (T) and serum bone alkaline phosphatase (P＜0.05) between the two groups after treatment,and the treatment group was superior to the control group.Conclusion Longniu Bugu Decoction can reduce bone loss in patients with premenopausal breast cancer caused by OFS combined with AIs therapy and improve patients' life quality.

Hotspots in text mining of biomedical field / 中华医学图书情报杂志

The high frequency subject terms were extracted from the PubMed-covered papers published from January 2000 to March 2015 on text mining of biomedical field to generate the matrix of high frequency subject terms and their source papers.The co-occurrence of high frequency subject terms in a same paper was analyzed by clustering analysis.The hotspots in text mining of biomedical field were analyzed according to the clustering analysis of high frequency subject terms and their corresponding class labels, which showed that the hotspots in text mining of bio-medical field were the basic technologies of text mining, application of text mining in biomedical informatics and in extraction of drugs-related facts.

Research Progress in Chemical Constituents of Qi-Gui-Yin Compound / 世界科学技术-中医药现代化

Qi-Gui-Yin (QGY) compound, which composes of five herbal medicines of Astragalus membranaceus (Fisch.) Bge., Angelica sinensis (Oliv.) Diels, Lonicera japonica Thunb., Artemisia annua L., and Polygonum cuspidatum Sieb.et Zucc., which is able to treat antibiotic-resistant bacteria with antibiotics, and also to delay or even reverse the bacterial resistance producing. However, QGY compound is a complex mixture. And it is very difficult to elaborate its material foundation. Therefore, chemical constituents in five herbal medicines were summarized through searching of the related literatures. And then, 170 kinds of bioactive ingredients were classi-fied in order to provide evidences for the study on chemical constituent of QGY compound and identify its mate-rial foundation of delaying drug resistance .