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Sorafenib was the first systemic therapy approved by the Food and Drug Administration to treat advanced hepatocellular carcinoma (HCC). However, sorafenib therapy is frequently accompanied by drug resistance. We aimed to explore the mechanisms of sorafenib resistance and provide feasible solutions to increase the response to sorafenib in patients with advanced HCC. The expression profile of discoidin domain receptor 2 (DDR2) in HCC tissues and cells was detected using quantitative real‐time PCR (qPCR) and western blotting assays. The effects of DDR2 on sorafenib resistance were examined using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, colony formation, TdT‐mediated dUTP nick end labeling, and flow cytometry assays. The effect of DDR2 on the nuclear factor kappa B (NF‐κB) signaling pathway was evaluated by luciferase reporter, immunofluorescence, qPCR and flow cytometry assays. We demonstrated that DDR2 expression was dramatically upregulated in sorafenib‐resistant HCC tissues relative to sensitive tissues. Downregulation of DDR2 sensitized HCC cell lines to sorafenib cytotoxicity. Further analysis showed that DDR2 could increase the nuclear location of REL proto‐oncogene, a NF‐κB subunit, to mediate NF‐κB signaling. Blocking NF‐κB signaling using the NF‐κB signaling inhibitor, bardoxolone methyl, increased the response of HCC cells to sorafenib. Further analysis showed that DNA amplification of DDR2 is an important mechanism leading to DDR2 overexpression in HCC. Our results demonstrated that DDR2 is a potential therapeutic target in patients with HCC, and targeting DDR2 represents a promising approach to increase sorafenib sensitivity in patients with HCC. [ABSTRACT FROM AUTHOR]

This study aims to systematically review the efficacy and safety of Shufeng Jiedu Capsules in the treatment of influenza. The randomized controlled trial(RCT) of Shufeng Jiedu Capsules alone or in combination with conventional western medicine for treating influenza were retrieved from PubMed, EMbase, Cochrane Library, Web of Science, SinoMed, CNKI, VIP, Wanfang, and ClinicalTrails.gov. The data analysis was performed in RevMan 5.4.1. The Cochrane risk of bias assessment tool was used to evaluate the quality of the involved RCT, and GRADEpro GDT to assess the quality of the evidence. A total of 11 RCTs involving 1 836 patients were included in this study. Compared with conventional western medicine, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.09, 95%CI[1.03, 1.15], P=0.002), shortened the time to relief of cough, and increased the 3-day sore throat relief rate, whereas there was no significant difference in the time to fever abatement, the time to relief of sore throat, 3-day cough relief rate, or 3-day runny nose relief rate. Subgroup-analysis showed that Shufeng Jiedu Capsules + conventional western medicine improved the response rate(RR=1.11, 95%CI[1.08, 1.15], P<0.000 01), shortened the time to relief of cough, and increased the 3-day relief rate of symptoms(cough, sore throat, and runny nose) compared with conventional western medicine alone, while there was no significant difference in the time to fever abatement or the time to relief of sore throat. Shufeng Jiedu Capsules alone could not improve the response rate(RR=0.97, 95%CI[0.93, 1.02], P=0.19). In addition, Shufeng Jiedu Capsules/Shufeng Jiedu Capsules + conventional western medicine vs conventional western medicine were no significant difference in adverse reactions(RR=0.98, 95%CI[0.57, 1.69], P=0.95). The available evidence suggests that Shufeng Jiedu Capsules is effective and safe in the treatment of influenza, and the combination of Shufeng Jiedu Capsules with conventional western medicine can accelerate the relief of symptoms. However, since the number and quality of the included studies were low, the above findings remained to be further verified by multicenter RCT with large sample sizes.

In order to improve the stability and catalytic activity of Fe-TAML, mono-6-oxy-cyclodextrin bonded Fe-TAML catalyst (CD-Fe-TAML) was prepared by bonding Fe-TAML with cyclodextrin (CD) through chlorosulfonylation reaction, metal chelation reaction, and nucleophilic substitution reaction. The catalytic activity and stability of CD-Fe-TAML and the oxidation degradation efficiencies of 34 organic micropollutants such as antibiotics and pesticides by activation of H 2 O 2 in water were studied. Compared with that of Fe-TAML, CD-Fe-TAML at pH 7.0 had a 49-fold and 25-fold increase in the rate of activating H 2 O 2 to produce iron (Ⅴ/Ⅳ)-oxo intermediates and the degradation rate of the substrate, respectively, and its self-oxidation rate was reduced by 70%. The stability of CD-Fe-TAML was 0.7-699 times higher than that of Fe-TAML in the pH range of 3.0-10.0. Specifically, the stability of CD-Fe-TAML was 33-699 times higher than that of Fe-TAML in the pH range of 3.0-7.0. The sulfonic acid group in the molecular structure of CD-Fe-TAML had an electrophilic effect, which could increase the positive charge density of Fe in the active center, accelerate the O-O bond cleavage of H 2 O 2 and the generation of iron(Ⅴ/Ⅳ)-oxo intermediates, improve the catalytic activity of Fe-TAML, and also improve its hydrolysis stability. Meanwhile, the CD group in the molecular structure had the "electron shuttle" effect and inclusion effect. The former could accelerate the electron transfer between the active center Fe-TAML and H 2 O 2 to improve the catalytic activity of Fe-TAML. The latter could inhibit the hydrolysis and self-oxidation of the active center Fe-TAML by inclusion or binding of the hydrolysis sites and oxidation sites, thus improving its stability. The degradation efficiencies of micropollutants by CD-Fe-TAML/H 2 O 2 under weakly acidic and neutral conditions (in the pH range of 5.0-7.0) were 0.4-59 times higher than those of Fe-TAML/H 2 O 2 . The degradation efficiencies of CD-Fe-TAML/H 2 O 2 on nine micropollutants with a molar volume less than 0.20 L·mol -1 , such as acetamiprid and sulfadiazine, were 0.3-1.1 times higher than that of Fe-TAML/H 2 O 2 at pH 8.0, and there were no significant differences between CD-Fe-TAML/H 2 O 2 and Fe-TAML/H 2 O 2 for micropollutants with a molar volume greater than 0.20 L·mol -1 . The results of iodide oxidation by CD-Fe-TAML/H 2 O 2 showed that I - was not oxidized to produce iodo-disinfection byproducts (I-DBPs). The degradation of micropollutants by CD-Fe-TAML/H 2 O 2 in the surface water sample was not disturbed by water components. The CD-Fe-TAML/H 2 O 2 system has a potential application in the removal of organic micropollutants from water.

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

In observational studies, herbal prescriptions are usually studied in the form of "similar prescriptions". At present, the classification of prescriptions is mainly based on clinical experience judgment, but there are some problems in manual judgment, such as lack of unified criteria, labor consumption, and difficulty in verification. In the construction of a database of integrated traditional Chinese and western medicine for the treatment of coronavirus disease 2019(COVID-19), our research group tried to classify real-world herbal prescriptions using a similarity matching algorithm. The main steps include 78 target prescriptions are determined in advance; four levels of importance labeling shall be carried out for the drugs of each target prescription; the combination, format conversion, and standardization of drug names of the prescriptions to be identified in the herbal medicine database; calculate the similarity between the prescriptions to be identified and each target prescription one by one; prescription discrimination is performed based on the preset criteria; remove the name of the prescriptions with "large prescriptions cover the small". Through the similarity matching algorithm, 87.49% of the real prescriptions in the herbal medicine database of this study can be identified, which preliminarily proves that this method can complete the classification of herbal prescriptions. However, this method does not consider the influence of herbal dosage on the results, and there is no recognized standard for the weight of drug importance and criteria, so there are some limitations, which need to be further explored and improved in future research.

Objective: To investigate the effect and mechanism of acupoint injection with 0.1% vitamin C+vitamin B complex solution (V C +V B Co) at "Tiantu" (CV 22), "Quchi" (LI 11) and "Zusanli" (ST 36) in mouse model of pneumonia induced by influenza A virus (A/PR/8/34 [H1N1], PR8)., Methods: Sixty male ICR mice were randomized into 6 groups, i.e. control group, model group, acupoint injection group, intraperitoneal injection group, non-target point group and ribavirin group, 10 mice in each one. Except the control group, the pneumonia models were induced by slow nasal dripping PR8 virus in the other groups. On the 2nd day of experiment, V C +V B Co solution, 40 μL was injected at "Tiantu" (CV 22), "Quchi" (LI 11, left) and "Zusanli" (ST 36, left) in the acupoint injection group; V C +V B Co solution, 120 μL was injected intraperitoneally in the intraperitoneal injection group; V C +V B Co solution, 40 μL was injected at non-target acupoints (0.5 cm away from "Tiantu" [CV 22] to the left side, "Quchi" [LI 11, left] and "Zusanli" [ST 36, left]) in the non-target point group; and ribavirin solution, 120 μL was injected intraperitoneally in the ribavirin group. The intervention was delivered once daily, for consecutive 7 days. Three parallel experiments were undertaken. The mean death rate and survival time were assessed in each group, the body mass and lung index were compared among groups. Using HE staining, the morphology of lung tissue was observed; and with real-time fluorescence quantitative PCR, viral load in lung tissue was detected. The concentrations of inflammatory factors (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, IL-10) were detected in lung tissue of each group using ELISA; and those of oxidative stress markers (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malondialdehyde [MDA]) were detected with chemiluminescence method., Results: Compared with the control group, the body mass was decreased and lung index was increased in the model group ( P <0.01). In comparison with the model group, body mass was increased in the acupoint injection group ( P <0.05), lung index was reduced in the acupoint injection group the and ribavirin group ( P <0.05); the mean death rate was decreased and the mean survival time prolonged in the mice of the acupoint injection group ( P <0.01, P <0.05); and the mean death rate was reduced in the mice of the ribavirin group ( P <0.05). In the model group, the alveolar structure was not integral, the alveolar septum was thickened, inflammatory cells were infiltrated and red blood cells exudated seriously ( P <0.01). Compared with the model group, in the acupoint injection group and the ribavirin group, the alveolar structure was integral, the thickened alveolar septum was alleviated; and the infiltration of inflammatory cells and the exudation of red blood cells were reduced remarkably. The viral load was reduced in the mice of the ribavirin group when compared with the model group ( P <0.01). Compared with the control group, the concentrations of TNF-α, IL-1β and MDA in lung tissue were increased and those of IL-10, SOD and GSH-Px were reduced in the model group ( P <0.01). In the acupoint injection group and the ribavirin group, the concentrations of TNF-α, IL-1β and MDA were reduced in lung tissue and those of IL-10, SOD and GSH-Px were increased ( P <0.05, P <0.01) when compared with the model group., Conclusion: Acupoint injection with V C +V B Co solution may alleviate inflammatory responses and oxidative stress in lung tissue of the PR8-induced pneumonia mice, improve survival rate and prolong the survival time in the case of no effect of the viral load.

This study aims to explore the efficacy and safety of Lianhua Qingwen preparations combined with Oseltamivir in the treatment of influenza patients. PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang, and VIP were searched for the randomized controlled trials(RCTs) involving the comparison between the influenza patients treated with Lianhua Qingwen preparations combined with Oseltamivir and those treated with Oseltamivir alone. Fever clearance time was taken as the primary outcome indicator. Clinical effective rate(markedly effective and effective), time to muscle pain relief, time to sore throat relief, time to cough relief, time to nasal congestion and runny nose relief, time to negative result of viral nucleic acid test, and adverse reactions were taken as the secondary outcome indicators. The data were extracted based on the outcome indicators and then combined. The Cochrane collaboration's tool for assessing risk of bias was used to evaluate the quality of a single RCT, and the grading of recommendations assessment, development and evaluations(GRADE) system to assess the quality of a single outcome indicator. RevMan 5.3 was employed to analyze data and test heterogeneity. Finally, 16 RCTs involving 1 629 patients were included for analysis. The Meta-analysis showed that Lianhua Qingwen preparations combined with Oseltamivir was superior to Oseltamivir alone in the treatment of influenza in terms of clinical effective rate(RR=1.16, 95%CI [1.12, 1.20], P&lt;0.000 01), fever clearance time(SMD=-2.02, 95%CI [-2.62,-1.41], P&lt;0.000 01), time to muscle pain relief(SMD=-2.50, 95%CI [-3.84,-1.16], P=0.000 2), time to sore throat relief(SMD=-1.40, 95%CI [-1.93,-0.85], P&lt;0.000 01), time to cough relief(SMD=-1.81, 95%CI [-2.44,-1.19], P&lt;0.000 01), time to nasal congestion and runny nose(SMD=-2.31, 95%CI [-3.61,-1.01], P=0.000 5), and time to negative result of viral nucleic acid test(SMD=-0.68, 95%CI [-1.19,-0.16], P=0.01). However, due to the low quality of the trials, the above conclusions need to be proved by more high-quality clinical studies. In addition, we still need to attach importance to the adverse reactions of the integrated application of Chinese and western medicines.

The present study evaluated the effectiveness and safety of Xuanfei Baidu Decoction(XFBD) for severe cases with coronavirus disease 2019(COVID-19).Forty-one patients(diagnosed as severe or critical type) admitted to Hubei Provincial Hospital of Integrated Chinese and Western Medicine and Wuhan Hospital of Traditional Chinese Medicine from February 1 to March 1, 2020, were included.All patients were treated with XFBD based on conventional therapies.Clinical outcomes, length of hospital stay, and lung CT images of patients were observed.Laboratory indicators were compared between admission and the 14 th day of treatment.Traditional Chinese medicine(TCM) symptoms and signs on the 7 th and 14 th days of treatment were also compared with baseline.The differences in clinical characteristics and clinical outcomes between XFBD and western medicine or conventional therapies were analyzed with the published trials on severe COVID-19 cases during the same period as external controls.According to the results, among the 41 cases, 40 were cured and discharged, and 1 died; the median length of hospital stay was 22 days, and the improvement rate of lung CT was 87.2%(34/39).Compared with the conditions on admission, the levels of white blood cells(WBC), C-reactive protein(CRP), fibrinogen(FIB), and lactate dehydrogenase(LDH) were reduced(P&lt;0.05, P&lt;0.01), and levels of procalcitonin(PCT), prothrombin time(PT), creatine kinase(CK), alanine aminotransferase(AST), total bilirubin(TBiL), and other indicators showed a downward trend.Moreover, symptoms like fever, cough, chest tightness/shortness of breath, dyspnea, head and body pain, anorexia, and greasy tongue coating were significantly improved on the 7 th and 14 th days of treatment(P&lt;0.05, P&lt;0.01), and fatigue was improved on the 14 th day of treatment(P&lt;0.01).The mortality, adverse reactions, and major events of the XFBD group were significantly lower than those of the western medicine and conventional treatment groups in the same period, and the usage of antibiotics, hormones, vasopressin, and invasive mechanical ventilation during treatment were generally less than other groups.In conclusion, XFBD has good efficacy and safety in the treatment of severe COVID-19 cases by improving inflammation and clinical symptoms, promoting the absorption of lung inflammation, and reducing mortality.

Objective: To observe the clinical effect of acupuncture on coronavirus disease 2019 (COVID-19) based on the conventional treatment., Methods: A total of 35 patients with COVID-19 of mild or ordinary type were involved (3 cases dropped off). Acupuncture was applied on the basis of western medicine and Chinese materia medica treatment. Dazhui (GV 14), Fengchi (GB 20), Kongzui (LU 6), Hegu (LI 4), etc. were selected as the main acupoints, the supplementary acupoints and the reinforcing and reducing manipulations were selected according to syndrome differentiation. Acupuncture treatment was given once a day, 5 times a week. On day 3 and day 7 of acupuncture, relief condition of the main symptoms was observed. Before acupuncture and on day 3 and day 7 of acupuncture, efficacy evaluation scale of TCM on COVID-19 (efficacy evaluation scale) score was recorded. The effects of different intervention time of acupuncture on patients' hospitalization time were compared, the understanding of acupuncture treatment of patients discharged from hospital was recorded, the clinical efficacy and safety of acupuncture treatment were evaluated., Results: On day 3 and day 7 of acupuncture, the symptoms of lung system and non lung system were both relieved; the scores of efficacy evaluation scale were both decreased compared before acupuncture ( P <0.05), and the efficacy evaluation scale score of day 7 of acupuncture were lower than day 3 of acupuncture ( P <0.05). The average hospitalization time of patients received early acupuncture was shorter than late acupuncture ( P <0.05). The total effective rate was 84.4% (27/32) on day 7 of acupuncture, which was higher than 34.4% (11/32) on day 3 of acupuncture ( P <0.05). During the acupuncture treatment, there were neither adverse reactions in patients nor occupational exposures in doctors. The patients generally believed that acupuncture could promote the recovery of COVID-19 and recommended acupuncture treatment., Conclusion: On the basis of the conventional treatment, acupuncture can effectively relieve the clinical symptoms in patients with COVID-19, early intervention of acupuncture can accelerate the recovery process. Acupuncture has good safety, clinical compliance and recognition of patients.

A new and expedient photocatalytic protocol for the construction of quinolin-2(1 H )-ones via Markovnikov-type sulfonylation/6-endo-trig cyclization/selective C(O)-CF 3 bond cleavage starting from N -alkyl- N -(2-ethynylphenyl)-2,2,2-trifluoroacetamides and sulfinic acids has been developed. It is as an unprecedented protocol for the preparation of 4-sulfonylquinoline-2(1 H )-ones with high efficiency, mild reaction conditions, acceptable yields and a wide range of substrates.

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of &quot; one prescription for single drug&quot;. This model refers to the R&D and registration system of modern drugs, and approximates to the &quot; law-abiding&quot; medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to &quot; establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research&quot;. Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of &quot; one prescription for single drug&quot; in the research and development of Chinese medicine. Additionally, a new type of &quot; series prescriptions&quot; was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

Inspired by Roush's pioneering work on rare sugars, we have developed a scalable, stereoselective, de novo synthesis of orthogonally protected C2-fluoro digitoxose and cymarose, utilizing Sharpless kinetic resolution and organocatalytic fluorination as key steps. The utility of this strategy is demonstrated by the synthesis of a fluorinated analogue of digoxin, which indicates the fluorine on the sugar ring may have a significant impact on biological activity.

Since narrative medicine was introduced in China, it has been widely used in medical education and clinical practice. The research on narrative medicine in China is especially characterized by its combination with traditional Chinese medicine(TCM). At present, the research on narrative medicine in China is still in the stage of small-scale practicing and theory advocating. Besides, there is also a lack of guidance on experimental design methodology for clinical application, which leads to few high-quality studies in this field. The present study reviewed the current high-quality research on narrative medicine to discuss the value and prospects of mixed methods research in narrative medicine. In addition, the common design, application procedures, and notes of mixed methods research were explained to provide references for the extensive applications of narrative medicine in the medical field, especially TCM clinical practice, education, and scientific research.