ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

ObjectiveTo explore the mechanisms of action of Ganlu Xiaodu Dan in treating viral pneumonia by combining network pharmacology and molecular docking with in vivo experimental validation. MethodsNetwork pharmacology and molecular docking were used to predict the core components， target genes， and major pathways of Ganlu Xiaodu Dan. Molecular docking was then applied to verify the interactions between the core components and key targets. Sixty male C57BL/6 mice were randomly divided into six groups （n = 10 per group）， including blank， model， dexamethasone， and Ganlu Xiaodu Dan low-， medium-， and high-dose groups. The blank and model groups were gavaged with physiological saline （10 mL·kg^-1） every 12 h. The dexamethasone group received intraperitoneal injections of dexamethasone （5 mg·kg^-1）. The low-， medium-， and high-dose groups of Ganlu Xiaodu Dan were gavaged with solutions at concentrations of 7.2， 14.4， and 21.6 g·kg^-1， respectively， every 12 h. Lung wet/dry weight ratio （W/D） was measured. Hematoxylin-eosin （HE） staining was used to observe pathological changes in lung tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to determine the expression levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-17， and IL-1β in bronchoalveolar lavage fluid （BALF）. Western blot was performed to detect the expression of phosphoinositide 3-kinase （PI3K） and protein kinase B （Akt） in lung tissue for further validation. ResultsTwelve potential active components of Ganlu Xiaodu Dan were identified through network pharmacology. A total of 306 overlapping target genes were obtained between Ganlu Xiaodu Dan and viral pneumonia. PPI network analysis identified the top 20 key targets， and GO and KEGG enrichment analyses revealed the top 20 signaling pathways. An “active component–target–pathway” network was constructed. Molecular docking demonstrated strong affinity between the core components of Ganlu Xiaodu Dan and key targets related to viral pneumonia. In animal experiments， compared with the blank group， the model group showed severe bronchial epithelial damage， disordered alveolar structure， massive inflammatory cell infiltration， widened alveolar septa， and obvious interstitial edema. W/D， levels of IL-1β， TNF-α， and IL-17 in BALF， and protein expression of p-PI3K/PI3K and p-Akt/Akt in lung tissue were all significantly increased （P<0.05）. Compared with the model group， lung injury in the Ganlu Xiaodu Dan groups and the dexamethasone group was alleviated. W/D and TNF-α levels were significantly decreased （P<0.05）. IL-1β and IL-17 levels were significantly reduced in the medium- and high-dose groups and the dexamethasone group， and the protein expression levels of p-PI3K/PI3K and p-Akt/Akt in lung tissue were significantly decreased （P<0.05）. ConclusionGanlu Xiaodu Dan can alleviate lung injury in viral pneumonia by suppressing the inflammatory response， and its mechanism may be related to the inhibition of PI3K/Akt pathway activation.

Objective:To investigate the effect of sanguinarine(SAG)on the intestinal epithelial barrier in septic rats and to explore the potential mechanism initially.Methods:Rats were divided into Sham group,CLP group,low-dose SAG group(L-SAG group),medium-dose SAG group(M-SAG group)and high-dose SAG group(H-SAG group)according to the random number table method,10 rats in each group.The rat model of sepsis was induced by cecum ligation puncture(CLP)method.HE staining was used to observe the pathological damage of intestinal epithelium.Serum DAO activity was detected by diamine oxidase(DAO)kit.Detec-tion of urinary lactose/mannitol(L/M)ratio by high performance liquid chromatography.Detection of serum TNF-α,IL-6 and IL-1β levels by ELISA.Protein expression levels in intestinal epithelial tissues were detected by Western blot.Results:The intestinal mucosa was intact and the intestinal villi were neatly arranged of rats in the Sham group;the intestinal mucosa of CLP group showed congestion and edema,inflammatory cell infiltration,irregular arrangement of intestinal villi,and enlarged villi gap;the pathological damage of intestinal mucosa in M-SAG group and H-SAG group were reduced to different degrees compared with the CLP group.Chiu's score,se-rum DAO activity and urinary L/M ratio were significantly higher in the CLP group compared with the Sham group;Chiu's score,se-rum DAO activity and urinary L/M ratio were significantly lower in the M-SAG and H-SAG groups compared with the CLP group(P<0.05).The serum TNF-α,IL-6 and IL-1β levels were significantly lower in the CLP group than in the Sham group,while the serum TNF-α,IL-6 and IL-1β levels were significantly higher in the M-SAG and H-SAG groups than in the CLP group(P<0.05).Claudin-3,ZO-1 and ocludin protein expressions were significantly lower in the intestinal epithelium of rats in the CLP group compared with the Sham group,while MLCK,MLC and p-MLC protein expressions were significantly increased.Compared with the CLP group,Claudin-3,ZO-1 and occludin protein expressions were significantly increased in the intestinal epithelium of rats in the M-SAG and H-SAG groups,while MLCK,MLC and p-MLC protein expressions were significantly decreased(P<0.05).Conclusion:SAG can reduce in-testinal barrier damage,inhibit intestinal barrier permeability,and protect intestinal barrier integrity in septic rats,which is at least partially achieved by inhibiting MLCK-MLC signaling pathway activation.

Objective:To investigate the effect of sanguinarine(SAG)on the intestinal epithelial barrier in septic rats and to explore the potential mechanism initially.Methods:Rats were divided into Sham group,CLP group,low-dose SAG group(L-SAG group),medium-dose SAG group(M-SAG group)and high-dose SAG group(H-SAG group)according to the random number table method,10 rats in each group.The rat model of sepsis was induced by cecum ligation puncture(CLP)method.HE staining was used to observe the pathological damage of intestinal epithelium.Serum DAO activity was detected by diamine oxidase(DAO)kit.Detec-tion of urinary lactose/mannitol(L/M)ratio by high performance liquid chromatography.Detection of serum TNF-α,IL-6 and IL-1β levels by ELISA.Protein expression levels in intestinal epithelial tissues were detected by Western blot.Results:The intestinal mucosa was intact and the intestinal villi were neatly arranged of rats in the Sham group;the intestinal mucosa of CLP group showed congestion and edema,inflammatory cell infiltration,irregular arrangement of intestinal villi,and enlarged villi gap;the pathological damage of intestinal mucosa in M-SAG group and H-SAG group were reduced to different degrees compared with the CLP group.Chiu's score,se-rum DAO activity and urinary L/M ratio were significantly higher in the CLP group compared with the Sham group;Chiu's score,se-rum DAO activity and urinary L/M ratio were significantly lower in the M-SAG and H-SAG groups compared with the CLP group(P<0.05).The serum TNF-α,IL-6 and IL-1β levels were significantly lower in the CLP group than in the Sham group,while the serum TNF-α,IL-6 and IL-1β levels were significantly higher in the M-SAG and H-SAG groups than in the CLP group(P<0.05).Claudin-3,ZO-1 and ocludin protein expressions were significantly lower in the intestinal epithelium of rats in the CLP group compared with the Sham group,while MLCK,MLC and p-MLC protein expressions were significantly increased.Compared with the CLP group,Claudin-3,ZO-1 and occludin protein expressions were significantly increased in the intestinal epithelium of rats in the M-SAG and H-SAG groups,while MLCK,MLC and p-MLC protein expressions were significantly decreased(P<0.05).Conclusion:SAG can reduce in-testinal barrier damage,inhibit intestinal barrier permeability,and protect intestinal barrier integrity in septic rats,which is at least partially achieved by inhibiting MLCK-MLC signaling pathway activation.

Objective To systematically evaluate the clinical efficacy of treatment based on intestine in the sepsis induced acute lung injury/acute respiratory distress syndrome(ALI/ARDS)under the traditional Chinese medicine theory"interior and exterior relationship between the lung and large intestine",and to provide evidence-based reference for clinical practice.Methods A computerized search of CNKI,Wanfang database,VIP database,China Biology Medicine disc(CBMdisc),Embase database of Dutch medical abstracts,PubMed database,Cochrane library database was performed to identify randomized controlled trial(RCT)that used the Tongfu method as an intervention for the treatment of ALI/ARDS induced by sepsis,published from the database establishment until October 8,2020.The control group was treated with conventional western medicine,and the test group was treated with the combination of Tongfu method and conventional western medicine.Screening of the literature and data extraction for those that met the inclusion criteria were performed by 2 investigators.The modified Jadad scale was used for quality assessment,and RevMan 5.4 and Stata 16.0 software were used for Meta analysis of the data.Results Thirteen articles were finally included,all of which were single center RCT studies,including 7 articles with≥4 points and 6 articles with<4 points.A total of 579 patients were included,290 in the test group and 289 in the control group.Meta-analysis showed that combined Tongfu treatment significantly increased the ALI/ARDS patient caused by sepsis oxygenation index[PaO2/FiO2;mean difference(MD)= 62.55,95%confidence interval(95%CI)was 55.74 to 69.37,P<0.05],reduced the levels of interleukin-6(IL-6;MD =-29.70,95%CIwas-48.34 to-11.06,P<0.05),tumor necrosis factor-α(TNF-α;MD=-2.94,95%CIwas-5.28 to-0.59,P<0.05),procalcitonin(PCT;MD =-1.34,95%CI =-2.17 to-0.51,P<0.05)and C-reactive protein(CRP;MD =-22.41,95%CIwas-36.52 to-8.29,P<0.05),reduced mechanical ventilation time(MD=-2.26,95%CIwas-2.86 to-1.66,P<0.05)and hospitalization time in intensive care unit(ICU;MD=-4.15,95%CIwas-7.47 to-0.84,P<0.05),reduced the 28-day mortality[relative risk(RR)= 0.43,95%CI was 0.24 to 0.76,P<0.05]and acute physiology and chronic health status scoreⅡ(APACHEⅡ;MD =-3.53,95%CI was-5.41 to-1.64,P<0.05).Conclusion Treatment based on intestine is valuable for reducing the condition and improving the prognosis of ALI/ARDS patients caused by sepsis,but further high-quality RCT studies are still needed to verify its efficacy and provide more accurate evidence-based evidence for clinical treatment.

Objective:To analyze the rules of medication and principles of formulas for the treatment of coronavirus disease 2019 (COVID-19) using the traditional Chinese medicine inheritance support platform (V2.5).Methods:The clinical data, including gender, age, clinical symptoms, frequency of traditional Chinese medicine medication and prescription information, of patients with COVID-19 and asymptomatic infection who were admitted to Hebei COVID-19 designated hospital supported by medical team of First Affiliated Hospital of Hebei University of Chinese Medicine from January to March 2021 were collected. The information data were input into the traditional Chinese medicine inheritance support platform (V2.5). The data mining and analysis were realized by the integrated association rules and complex entropy clustering analysis methods of the software, including the analysis of the frequency of each drug use, drug meridian, taste, and prescription rules, and the new prescriptions were developed.Results:A total of 564 patients (564 prescriptions) were enrolled, involving 200 Chinese herbs, including 357 cases of common COVID-19 and 207 cases of asymptomatic infection. The proportion of women with common COVID-19 was high, and the high incidence age group was 51-70 years old. There was no significant difference in gender of asymptomatic infection, and the high incidence age group was 1-20 years old. The main clinical manifestations of most patients were head heavy and cough, followed by low fever and cough with sputum, the main tongue coating and pulse pattern were similar in both types of patients. The frequency of traditional Chinese medicine used in patients with common type of COVID-19 from high to low was liquorice root (326 times), indian bread (264 times), pinellia tuber (263 times), bitter apricot seed (236 times), baical skullcap root (229 times), gypsum (205 times), agastache rugosus (201 times), dried tangerine peel (194 times), ephedra (184 times), and Chinese thorowax root (163 times), while that used by asymptomatic infection were baical skullcap root (174 times), liquorice root (142 times), medicated leaven (137 times), agastache rugosus (127 times), pinellia tuber (114 times), Chinese thorowax root (100 times), officinal magnolia bark (91 times), atractylodes rhizome (89 times), peony root (84 times), and milkvetch root (83 times). The two types of patients were mainly treated with warm, cold and flat drugs, and the nature and taste were mainly pungent, bitter and sweet. The meridian tropism of drugs was mainly lung, spleen and stomach. High frequency drug formulation mainly included drugs for resolving turbidity and detoxification. At the same time, seven new prescriptions for common COVID-19 and four new prescriptions for asymptomatic infection were developed.Conclusions:The primary reason for the COVID-19 occurrence and development is turbidity-toxin and the qi of plague, and resolving turbidity and detoxication are the basic treating principle. On the basis, for patients with common COVID-19, symptomatic treatment such as relieving exterior syndrome, clearing heat, resolving phlegm, and antitussive drugs should be taken into account at the same time, while the treatment of asymptomatic infections should focus more on supporting the body and eliminating the harmful pathogens.

Objective:To evaluate the clinical efficacy and safety of combination of traditional Chinese and Western medicine in the treatment of coronavirus disease 2019 (COVID-19) by Meta analysis.Methods:The clinical randomized controlled trials (RCT) and cohort studies on the treatment of COVID-19 with combination of Chinese traditional and Western medicine published on CNKI, Wanfang database, VIP database and PubMed were searched by computer from January 2020 to June 2020. Patients in the simple Western medicine treatment group were treated with routine treatment of Western medicine, and the patients in integrated traditional Chinese and Western medicine treatment group were treated with traditional Chinese medicine on the basis of routine treatment of Western medicine. The main outcome was the total effective rate of treatment. The secondary outcome were the antipyretic rate, chest CT recovery rate, lymphocyte count (LYM), C-reactive protein (CRP) level and safety. The Cochrane manual and the Newcastle Ottawa Scale (NOS) were used to evaluate the quality of the literature; the RevMan5.3 software was used to analyze the articles that meets the quality standards, and a funnel chart was drawn to evaluate the total effective publication bias.Results:Thirteen articles were analyzed, including 1 039 COVID-19 patients, 559 in integrated traditional Chinese and Western medicine treatment group and 480 in simple Western medicine treatment group. The results of Meta-analysis showed that compared with the simple Western medicine treatment group, the combination of routine treatment of Western medicine and traditional Chinese medicine Qingfei Paidu decoction, Lianhua Qingwen granule, Shufeng jiedu capsule, Xuebijing injection or Reyanning mixture could significantly improve the total effective rate, antipyretic rate and chest CT recovery rate [total effective rate: odds ratio ( OR) = 2.95, 95% confidence interval (95% CI) was 2.10-4.14, P < 0.000 01; antipyretic rate: OR =3.01, 95% CI was 1.64-5.53, P = 0.000 4; chest CT recovery rate: OR = 2.53, 95% CI was 1.83-3.51, P = 0.000 1], increase LYM levels [mean difference ( MD) = 0.26, 95% CI was 0.02-0.50, P = 0.03], and reduce of CRP content ( MD = -17.68, 95% CI was -33.14 to -2.22, P = 0.02). Based on the funnel chart analysis of 12 articles with total efficiency, the result showed that the funnel chart distribution was not completely symmetrical, indicating that there might be publication bias. Conclusions:On the basis of routine treatment with Western medicine, combined with traditional Chinese medicine can significantly improve the total effective rate of COVID-19 and improve the laboratory results and clinical symptoms of patients. Compared with the routine treatment of Western medicine alone, the combination of traditional Chinese and Western medicine has better clinical efficacy and safety.

Objective:To analyze the data of Chinese medicine prescriptions for the treatment of coronavirus disease 2019 (COVID-19) in Shijiazhuang City, Hebei Province, with a view to further guide the clinical use of Chinese medicine in the prevention and treatment of COVID-19.Methods:Forty-eight patients diagnosed with COVID-19 who were treated by critical care team of Hebei Traditional Chinese Medicine Hospital in the intensive care unit (ICU) of Hebei Chest Hospital (Hebei Provincial COVID-19 designated hospital) from January 7 to March 4, 2021, were enrolled in this study. The patients' gender, age, clinical classification, past history, and all Chinese medicine prescriptions for the first visit and follow-up visits during the hospitalization were collected. A database was established based on the Ancient and Modern Medical Records Cloud Platform (V2.2.1), and the methods of frequency analysis, correlation analysis, cluster analysis, and complex network analysis were used to analyze the prescriptions of traditional Chinese medicine.Results:Among the 48 patients with COVID-19, 20 were males and 28 were females; the average age was (62.4±13.7) years old. The patients' condition was generally severe, including 17 cases of common type, 25 cases of severe type, and 6 cases of critical type, most of whom were combined with hypertension, coronary heart disease, diabetes, chronic obstructive pulmonary disease and other basic illnesses. A total of 146 valid prescriptions were included, involving 59 prescriptions and 115 Chinese medicines. Frequency analysis of 146 prescriptions showed that the commonly used prescriptions for patients with COVID-19 were Qingfei Paidu decoction (30 times, 20.55%), Xuanbai Chengqi decoction (10 times, 6.85%), and Dayuan Yin (10 times, 6.85%). The common Chinese medicines were liquorice (80 times, 54.79%), tuckahoe (76 times, 52.05%), gypsum (70 times, 47.95%), bitter almond (70 times, 47.95%), ephedra (57 times, 39.04%), scutellaria (56 times, 38.36%), tangerine peel (53 times, 36.30%), patchouli (50 times, 34.25%), atractylodes macrocephala (50 times, 34.25%), and bupleurum (43 times, 29.45%). The main effects were clearing heat and detoxification (129 times), clearing heat-fire (129 times) and eliminating dampness and diuresis (110 times). The medicinal properties were mainly warm (509 times), flat (287 times), and cold (235 times). The medicinal tastes were mainly pungent (765 times), sweet (654 times), and bitter (626 times). The medicinal channel tropism were mainly lung (1 096 times), spleen (785 times), and stomach (687 times). The correlation analysis showed that there were 17 drug combinations in total, among which the top 3 drug pairs in support were bitter almond-gypsum (0.43), ephedra-bitter almond (0.38), tangerine peel-poria (0.36), and ephedra-gypsum (0.36). Cluster analysis showed that there were 3 groups of clustering formulas. The first group was ephedra, bitter almond, and gypsum. The second group was patchouli, tuckahoe, tangerine peel, and atractylodes macrocephala. The third group was scutellaria, licorice, immature orange fruit, oriental waterplantain rhizome, bupleurum, ginger, and cassia twig. The core drugs were composed of tuckahoe, bupleurum, tangerine peel, atractylodes macrocephala, patchouli, bitter almond, scutellaria, gypsum, ephedra, and licorice.Conclusions:Middle-aged and elderly patients with COVID-19 are accompanied by Qi deficiency and internal invasion of toxins, and the pathogenesis evolves rapidly. Damp and turbid toxins often block the lungs and trap the spleen, leading to disorder of Qi movement, and even invaginate Ying and Xue, drain Yin and Yang. The treatment is based on removing turbidity and detoxification, and replenishing Qi and nourishing Yin are the principle treatments, so that the evil is eliminated and the Qi is restored.

2019 Novel coronavirus (2019-nCoV) infection caused a pandemic in the world. From the reported cases in the literatures, the level of D-dimer in patients with coronavirus disease 2019 (COVID-19) is positively correlated with the severity of illness, which needs the attention of clinical workers. According to Western medicine, the increase of D-dimer is related to the hyperactivity of fibrinolytic system and the shortening of prothrombin time (PT), resulting in excessive production and degradation of plasma fibrin and hypercoagulable state of blood, while traditional Chinese medicine (TCM) believes that the above syndromes belong to the pathogenesis of "blood stasis" according to TCM theories. Over the years, TCM has a significant effect on promoting blood circulation, removing blood stasis and improving microcirculation. This article reviews the mechanism, clinical significance, understanding of TCM and common methods of promoting blood circulation and removing blood stasis caused by 2019-nCoV, in order to provide ideas for the prevention and treatment of impaired blood coagulation in patients with COVID-19.

Objective:To analyze the research status, research hotspots and frontier trends of traditional Chinese medicine (TCM) in the treatment of influenza in the past 20 years through the knowledge graph, so as to provide reference basis for further research.Methods:The related literatures of TCM in the treatment of influenza were collected in China National Knowledge Infrastructure (CNKI) from 2000 to 2019. The relevant graphs of authors, research institutions and key words were drawn by CiteSpace 5.6, the distribution and cooperation of main research forces in this field were analyzed, and the research frontiers and hot spot information in this field were discussed.Results:A total of 3 048 related literatures were obtained, involving 949 authors and 242 research institutions. The analysis of the number of articles showed that the volume of articles related to the treatment of influenza with TCM fluctuated greatly in the past 20 years, which was obviously affected by the sudden hot spots around 2010, but showed an overall upward trend, with an average annual volume of about 152 articles. The analysis of the author's cooperation map showed that a total of 77 core authors had published more than 5 articles, accounting for only 8.1% of all authors, and 5 authors had published more than 30 articles. Five major teams had been formed with Gu Ligang, Liu Qingquan, Lu Fangguo, Cui Xiaolan and Zhang Fengxue as the core. The analysis of the cooperation map of research institutions showed that the cooperation among institutions was not good, and only the scientific research institutes in Beijing and Guangzhou had formed a closely related cooperation network. The keyword co-occurrence map showed that 8 keywords appeared more than 100 times, especially ultra-high-frequency keywords, influenza virus ranked first ( n = 518). There were 14 key nodes, such as influenza virus, TCM treatment, viral pneumonia and so on, which supported the current research field of TCM in the treatment of influenza. Fourteen clusters were formed to classify the current research hotspots, including the nomenclature of influenza, virus type, TCM treatment, western medicine knowledge, etc., and the map showed that the clustering was reasonable and the structure was significant. Timeline graph showed that parainfluenza virus, virus disease, pharmacodynamics, heat-clearing and detoxifying drugs, bacteriostasis and experimental research had all been studied for more than 8 years, revealing the research hotspots and trends of TCM in the treatment of influenza. Conclusions:The overall research related to the treatment of influenza with TCM is relatively perfect. In the future, the close cooperation among authors and institutions should be strengthened. The molecular mechanism research, clinical and animal trials of TCM should be further studied, so as to improve the research system of TCM treatment of influenza.