Expert consensus on the use of traditional Chinese medicine for the treatment of common symptoms of post-COVID-19 short-term condition.

A proportion of patients who recovered from COVID-19 have ongoing, recurrent, or new symptoms with negative nucleic acid/antigen test results, which has become a new public health problem that needs to be concerned. Traditional Chinese medicine (TCM) has shown its unique advantages in preventing, treating, and rehabilitating COVID-19. To further standardize clinician's clinical diagnosis and use of TCM for the treatment of common symptoms associated with COVID-19 infection following negative nucleic acid/antigen results, the front-line clinical experts were invited for discussion on the concepts, etiology, clinical manifestations of post-COVID-19 condition, and on treatment with TCM to form the consensus. Clinicians of TCM, Western medicine, or integration of both can use this consensus document for clinical practice and research purposes.

[Optimization of alcohol precipitation technology of Biqiu granules based on index components and pharmacodynamics].

To evaluate the rationality of alcohol precipitation technology of Biqiu granule by investigating its effect on serum histamine, IgE, IL-4, IFN and TNF-α. The contents of cafferic acid and rosmarinic acid were used as the evaluation indexes, and some factors affecting index were firstly evaluated by Plackett-Burman design; then alcohol precipitation technology was further optimized by Box-Behnken design to determine the optimal alcohol precipitation conditions. The best alcohol precipitation conditions were as follows: the relative density of herb liquor was 1.15 (65 ℃); the concentration of alcohol was 70%, and standing time was 12 hours. Optimal alcohol precipitation technology of Biqiu granules determined by pharmacodynamic screening, Plackett-Burman and Box-Behnken design tests, was stable and feasible with good predictability, providing reliable basis for the industrialization production of Biqiu granules.

Effects of Feiwei granules in the treatment of idiopathic pulmonary fibrosis: a randomized and placebo-controlled trial.

OBJECTIVE: To document the therapeutic effects of Feiwei granules (FGs) for idiopathic pulmonary fibrosis (IPF). METHODS: One hundred cases with IPF were randomized into the treatment group (80) and control group (20). Both groups were given basic treatment with prednisone. The treatment group was given FGs, and the control group was given Jinshuibao capsules (JCs). Treatment lasted for 6 months. The Medical Research Council Dyspnea Scale (MRCDS), the Saint George's Hospital Respiratory Questionnaire (SGHRQ), pulmonary function, the Traditional Chinese Medicine Syndrome Score (TCMSS), 6-min walking test (6MWT) and blood gas analyses were recorded before the study as well as 3 months and 6 months after treatment. RESULTS: FGs showed greater efficacy than the control in certain parameters between before the study and 6 months, and between 3 months and 6 months, in the MRCDS, some indicators in the SGHRQ, and the TCMSS. There were no significant differences between the treatment group and control group in the remainder of the indices evaluated. In the treatment group, there were significant differences in before and after treatment in the MRCDS, SGHRQ, TCMSS and 6MWT. CONCLUSION: FGs were similar to JCs for IPF treatment.

[Optimization of one-step pelletization technology of Biqiu granules by Plackett-Burman design and Box-Behnken response surface methodology].

First with the qualified rate of granules as the evaluation index, significant influencing factors were firstly screened by Plackett-Burman design. Then, with the qualified rate and moisture content as the evaluation indexes, significant factors that affect one-step pelletization technology were further optimized by Box-Behnken design; experimental data were imitated by multiple regression and second-order polynomial equation; and response surface method was used for predictive analysis of optimal technology. The best conditions were as follows: inlet air temperature of 85 degrees C, sample introduction speed of 33 r x min(-1), density of concrete 1. 10. One-step pelletization technology of Biqiu granules by Plackett-Burman design and Box-Behnken response surface methodology was stable and feasible with good predictability, which provided reliable basis for the industrialized production of Biqiu granules.

[Optimization of spraying dry technology of Biqiu ranules ethanol extract by Box-Behnken response surface method].

With inlet temperature, specific gravity, feeding speed as independent variables, the comprehensive evaluating indexes of content of schisandrin and arctiin as dependent variable, the experimental data were fitted to a second order polynomial equation. Based on establishing the mathematical relationship between the comprehensive evaluating indexes and respective variables, Box-Benhnken central composite test and response surface analysis method was employed to optimize the spray drying technology of Biqiu granules ethanol extract. The optimal drying parameter was as follows: the inlet temperature was 175 degrees C, the specific gravity was 1.10, feeding speed was 32 r x min(-1). Under these conditions, the comprehensive evaluating indexes of spraying dry processes was 92.68, which was close to the model prediction. The spraying dry technology of Biqiu granules ethanol extract optimized by response surface methodology was accurate and feasible, which provided theoretical experiment basis for the industrialization production.

[The expression of the inflammation-related cytokines in pneumonia mice infected with influenza virus and regulation of Shufengxuanfei and Jiebiaoqingli herbal anti-virus formulas].

OBJECTIVE: To investigate the expression of the inflammation-related cytokines in pneumonia mice infected with influenza virus and regulation of Shufengxuanfei(SFXF) and Jiebiaoqingli (JBQL) Chinese herbal anti-virus formulas. METHODS: Mice were anesthetized and then infected intranasally by dropping 0.05 mL of influenza virus suspension (4×LD50;) except normal group. Mice were divided randomly into nine groups: normal group, model group (virus only), control group [11.375 g/(kg.d)Oseltamivir], low-dose SFXF [0.94 g/(kg.d)], medium-dose SFXF [1.88 g/(kg.d)], high-dose SFXF [3.76 g/(kg.d)], low-dose JBQL [1.09 g/(kg.d)], medium-dose JBQL [2.18 g/(kg.d)] and high-dose JBQL [4.36 g/(kg.d)]. Oseltamivir group, SFXF groups and JBQL groups were administered to mice by oral gavage in equal dose of 0.2 mL daily for 4 consecutive days, while the rest of the groups received water only. Total RNA was extracted in each group. Then gene chips were used to screen these RNA samples. Select differentially expressed genes of cytokines involved in inflammation. Some candidate genes, such as IL-1ß, IL-8, IL-10, RANTES and ICAM-1 were verified by qRT-PCR. To confirm the genes expression data from the microarray involved in inflammation in response to virus infection and treatment, we used qPCR to verify mRNA relative expressions of IL-1ß, IL-8, IL-10, RANTES and ICAM-1. The expression of IL-1ß protein in lung tissues was verified by Western blotting. RESULTS: IL-1ß, CXCR2, CCL5, IL-10, IL-6, IL-18, TGF-ß1 and CCL2 were up-regulated in model group. Gene expressions of IL-1ß, CXCR2, CCL5, IL-10 and IL-6 were significantly down-regulated by all therapeutic groups. SFXF in medium-dose and low-dose down-regulated gene expressions of IL-18, TGF-ß1, CCL2 and CCL5. IL-18 and CCL5 was down-regulated by both low-dose and medium-dose JBQL. qRT-PCR and western blot experiments showed that two formulas in medium-dose can down-regulate mRNA and protein expression of IL-1ß (P<0.01). Both SFXF and JBQL in medium-dose significantly decreased the IL-8, RANTES, ICAM-1 and IL-10 mRNA expression (P<0.05 or P<0.01), compared with the model group. As expected, qRT-PCR data were in good agreement with the microarray assay. CONCLUSION: The two anti-viral formulas may inhibit inflammatory immunopathogenesis, and may have the actions of protection the lung tissue from influenza-induced injury.

Gene Expression Profiles Underlying Selective T-Cell-Mediated Immunity Activity of a Chinese Medicine Granule on Mice Infected with Influenza Virus H1N1.

A Chinese medicine granule, Shu-Feng-Xuan-Fei (SFXF), is critical for viral clearance in early phase of influenza virus infection. In this study, 72 ICR mice were randomly divided into six groups: normal control group, virus control group, Oseltamivir group, low-dose SFXF, medium-dose SFXF, and high-dose SFXF. Mice were anesthetized and inoculated with 4LD50 of influenza virus A (H1N1) except normal control group. Oseltamivir group received 11.375 mg·kg(-1) ·d(-1) Oseltamivir Phosphate. SFXF 3.76, 1.88 and 0.94 g·kg(-1) ·d(-1) were administrated to mice in all SFXF groups. Each group was in equal dose of 0.2ml daily for 4 consecutive days. Mice were sacrificed and then total RNA was extracted in lung tissue. Some genes involved in T-cell-mediated immunity were selected by DNA microarray. These candidate genes were verified by Real-Time PCR and western immunoblotting. Compared with virus control group, in Toll-like receptor signaling pathway, 12 virus-altered genes were significantly reduced following medium-dose SFXF treatment. Eighteen antigen processing presentation-associated genes were upregulated by medium-dose SFXF. In the process of T cell receptor signaling pathway, 19 genes were downregulated by medium-dose SFXF treatment. On exploration into effector T cells activation and cytokines, all of altered genes in virus control group were reversed by medium-dose SFXF. Real-time PCR and western immunoblotting showed that the regulation of medium-dose SFXF in IL-4, IFN-γ, TNF-α, IL-1ß, TLR7, MyD88, p38, and JNK was superior to Oseltamivir and high-dose SFXF group. Therefore, SFXF granules could reduce influenza infected cells and activation of T cells.

A network-based systematic study for the mechanism of the treatment of zhengs related to cough variant asthma.

Traditional Chinese medicine (TCM) has shown significant efficacy in the treatment of cough variant asthma (CVA), a special type of asthma. However, there is shortage of explanations for relevant mechanism of treatment. As Zhengs differentiation is a critical concept in TCM, it is necessary to explain the mechanism of treatment of Zhengs. Based on TCM clinical cases, this study illustrated the mechanism of the treatment of three remarkably relevant Zhengs for CVA: "FengXieFanFei," "FeiQiShiXuan", and "QiDaoLuanJi." To achieve this goal, five steps were carried out: (1) determining feature Zhengs and corresponding key herbs of CVA by analyses of clinical cases; (2) finding out potential targets of the key herbs and clustering them based on their functional annotations; (3) constructing an ingredient-herb network and an ingredient network; (4) identifying modules of the ingredient network; (5) illustrating the mechanism of the treatment by further mining the latent biological implications within each module. The systematic study reveals that the treatment of "FengXieFanFei," "FeiQiShiXuan," and "QiDaoLuanJi" has effects on the regulation of multiple bioprocesses by herbs containing different ingredients with functions of steroid metabolism regulation, airway inflammation, and ion conduction and transportation. This network-based systematic study will be a good way to boost the scientific understanding of mechanism of the treatment of Zhengs.

[Effect of shufeng xuanfei recipe and jiebiao qingli recipe on mRNA and protein expressions of TLR7, MyD88, and NF-kappaB in mice infected with influenza virus].

OBJECTIVE: To observe effect of Shufeng Xuanfei Recipe (SXR) and Jiebiao Qingli Recipe (JQR) on mRNA and protein expressions of Toll-like receptor 7 (TLR7), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappaB (NF-kappaB) in mice infected with influenza virus FM1. METHODS: One hundred and eight mice were randomly divided into nine groups, i.e., the normal control group, the model group, the Oseltamivir group (at the daily dose of 2.5 g/mL), the high dose SXR group (at the daily dose of 3.762 g/kg), the middle dose SXR group (at the daily dose of 1.881 g/kg), the low dose SXR group (at the daily dose of 0.941 g/kg), the high dose JQR group (at the daily dose of 4.368 g/kg), the middle dose JQR group (at the daily dose of 2.184 g/kg), and the low dose JQR group (at the daily dose of 1.092 g/kg), 12 in each group. All mice were mildly anesthetized by ether. Mice in the normal control group were treated by nasal drop of 0.05 mL normal saline, while mice in the rest groups were infected by nasal drop of 0.05 mL influenza virus strain FM1 (LD50). The successful modeling rate was 100%. All medication was performed by gastrogavage 2 h after infection. Distilled water was given by gastrogavage to mice in the normal control group and the model group at the daily dose of 0.2 mL, each time per day for 4 successive days. mRNA expressions of TLR7, MyD88, and NF-kappaB in the lung tissue were determined by Western blot. RESULTS: Compared with the normal control group, mRNA expressions of TLR7, MyD88, and NF-kappaB increased in the model group (P < 0.01). Compared with the model group, mRNA and protein expressions of TLR7, MyD88, and NF-kappaB decreased in the Oseltamivir group, the high, middle, and low dose SXR groups (P < 0.05, P < 0.01); mRNA and protein expressions of TLR7 and NF-kappaB decreased in the high and middle dose JQR groups (P < 0.05, P < 0.01); mRNA expressions of MyD88 decreased in the high and middle dose JQR groups (P < 0.05); protein expressions of MyD88 decreased in the middle dose JQR group (P < 0.05); protein expressions of TLR7 and NF-kappaB decreased in the low dose JQR group (P < 0.05). Compared with the Oseltamivir group, protein expressions of MyD88 decreased in the low dose SXR group (P < 0.05); protein expressions of NF-kappaB decreased in the middle and low dose SXR groups (P < 0.01); mRNA and protein expressions of TLR7 (P < 0.05, P < 0.01), and protein expressions of MyD88 (P < 0.01) decreased in the high, middle, and low dose JQR groups; mRNA and protein expressions of NF-kappaB decreased in the low dose JQR group (P < 0.05, P < 0.01). CONCLUSIONS: Each dose SXR and middle dose JQR could down-regulating the activity of NF-kappaB through adjusting MyD88 dependent TLR signal pathway, thus fighting against influenza virus. SXR was more effective than JQR.

[Screening for genes associated with natural killer cell mediated cytotoxicity in pneumonia mice infected with influenza virus and regulation of two herbal anti-virus formulas].

OBJECTIVE: To investigate the regulation of two herbal anti-virus formulas on gene expression profile associated with natural killer cell (NK cell) mediated cytotoxicity in pneumonia mice infected with influenza virus. METHODS: According to random number table, 90 ICR mice were divided into nine groups with 10 mice in each group: normal group (N), model group (M), oseltamivir group (control group, C), low-dose, medium-dose and high-dose Shufeng Xuanfei formula groups (SL, SM, SH groups), and low-dose, medium-dose and high-dose Jiebiao Qingli formula groups (JL, JM, JH groups). The model of pneumonia was reproduced by nasal dropping influenza virus A (FM1) in mice. N group was given isotonic saline 0.05 ml in nasal drops. After 2 hours of model-building, C group was received 11.375 mg×kg⁻¹×d⁻¹ oseltamivir phosphate. Shufeng Xuanfei formula (mainly honeysuckle, forsythia and radix isatidis, etc.) with 3.76, 1.88 and 0.94 g×kg⁻¹×d were administrated to SH, SM and SL groups by gastric irrigation respectively. Jiebiao Qingli formula (mainly ephedra, gypsum, glycyrrhiza glabra, etc.) with 4.36, 2.18 and 1.09 g×kg⁻¹×d⁻¹ were administrated to JH, JM and JL groups by gastric irrigation respectively. In N and M groups, normal saline was administrated with gastric perfusion. Each group was in equal dose of 0.2 ml daily over a 4-day period. Total RNA in lung tissue of mice were extracted in each group, then gene chips were used to screen these RNA samples. Some genes involved NK cell mediated cytotoxicity were selected, with "I" representing of signal intensity. These candidate genes were verified by real-time fluorescent quantitation polymerase chain reaction (PCR) and Western blotting. RESULTS: In the pathway of NK cell mediated cytotoxicity, M group up-regulated 43 genes expression, and 36, 29, 22, 21, 20 and 10 genes showed down-regulation in SM, JM, SL, JH, SH and JL groups, respectively. Apart from gene co-expression network in SH, SL, JH, JM and JL, SM also expressed other differential genes which SH, SL, JH, JM and JL did not. So medium-does Shufeng Xuanfei formula had the most significant regulation in gene expression of NK cell mediated cytotoxicity. By real-time PCR and Western blotting experiments showed that compared with the M group, mRNA and protein expression of tumor necrosis factor-α (TNF-α) in these two formula groups were significantly down-regulated, especially prominent in SM group and JM group (TNF-α mRNA: 1.07 ± 0.19, 1.19 ± 0.14 vs. 3.20 ± 0.56, both P<0.01). CONCLUSIONS: Influenza viral replication in host cell, which means influenza antigens exposure in infected cells as target cells. NK cells recognize and exert cell mediated cytotoxic function against influenza antigens. Genes associated with NK cell mediated cytotoxicity in influenza infection were up-regulated. Shufeng Xuanfei and Jiebiao Qingli formulas could down-regulate these genes. The mechanism of down-regulated genes is that the number of influenza infected cells and NK cells activation decreases in treatment with two formulas.