Clinical effects of Shenxie Zhitong Capsules combined with DONG's Extraordinary Points on patients with knee osteoarthritis of Cold-Dampness Obstruction Pattern / 中成药

AIM To explore the clinical effects of Shenxie Zhitong Capsules combined with DONG's Extraordinary Points on patients with knee osteoarthritis of Cold-Dampness Obstruction Pattern.METHODS Eighty patients were randomly assigned into control group(40 cases)for 1-month intervention of DONG's Qi Point,and observation group(40 cases)for 1-month intervention of both Shenxie Zhitong Capsules and DONG's Qi Point.The changes in clinical effects,TCM syndrome scores,LKSS score,WOMAC score,NRS score,AIMS2-SF score,sIL-4R,TNF-α,HMGBl,TLR-4,BALP,BGP and β-CTX were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,WOMAC score,NRS score,sIL-4R,TNF-α,HMGBl,TLR-4,β-CTX(P＜0.05),and increased LKSS score,AIMS2-SF score,BALP,BGP(P＜0.05),especially for the observation group(P＜0.05).CONCLUSION For the patients of Cold-Dampness Obstruction Pattern,Shenxie Zhitong Capsules combined with DONG's Extraordinary Points can inhibit body inflammatory responses,improve bone metabolism,and relieve knee pain and clinical symptoms.

Differential Study on Intestinal Flora between Knee Osteoarthritis with Dampness-heat Obstruction Syndrome and Cold-dampness Blockage Syndrome Based on 16S rDNA Sequencing Technology / 中国中医药信息杂志

Objective To compare the differences in the composition and diversity of intestinal flora between knee osteoarthritis(KOA)patients with dampness-heat obstruction syndrome,cold-dampness blockage syndrome and healthy people;To explore the characteristics of intestinal flora of KOA patients with the above two TCM syndrome types.Methods According to the inclusion and exclusion criteria,dampness-heat obstruction syndrome group,cold-dampness blockage syndrome group,and healthy control group were screened,with 10 cases for each group,and then their fecal samples were collected.16S rDNA sequencing technology was used to compare the differences of intestinal flora among groups by Alpha and Beta diversity analysis.Results There was no significant difference in species richness of intestinal flora among the three groups,but there was statistical significance in species diversity between cold-dampness blockage syndrome group and dampness-heat obstruction syndrome group,and healthy control group(P<0.05).There were statistical significance among the three groups in intestinal flora composition(P= 0.001).At the phylum level,Bacteroidota and Firmicutes were significantly dominant,and at genus level,the abundance of Prevotella in dampness-heat obstruction syndrome group and cold-dampness blockage syndrome group increased.The abundance of Enterobacteriaceae,Lachnospira and Klebsiella was relatively large in dampness-heat obstruction syndrome group.The abundance of Prevotella and Pseudomonas in cold-dampness blockage syndrome group was large.Conclusion There are differences in the intestinal flora structure between KOA patients with dampness-heat obstruction syndrome and cold-dampness blockage syndrome.

Alterations in intestinal microbiota and enzyme activities under cold-humid stress: implications for diarrhea in cold-dampness trapped spleen syndrome.

Introduction: Cold and humid environments alter the intestinal microbiota, and the role of the intestinal microbiota in the development of diarrhea associated with cold-dampness trapped spleen syndrome in Chinese medicine is unclear. Methods: The 30 mice were randomly divided into normal and model groups, with the model group being exposed to cold and humid environmental stresses for 7 days. Then, mouse intestinal contents were collected and analyzed their intestinal microbiota and digestive enzymes. Results: Our findings revealed significant increases in sucrase and lactase activities, as well as microbial activity, in the model group (p < 0.05). ß-diversity analysis highlighted distinct intestinal microbiota compositions between the two groups. Specifically, the experimental group showed a unique dominance of the genera and strains Clostridium sensu stricto 1 and Clostridium sp. ND2. LEfSe analysis identified Helicobacter, Roseburia, and Eubacterium plexicaudatum ASF492 as differentially abundant species in them model group. Network analysis demonstrated that rare bacterial species mostly governed the microbial interactions, exhibiting increased mutual promotion. On the other hand, abundant species like Lactobacillus johnsonii and Lactobacillus reuteri showed mutual inhibitory relationships. Discussion: In summary, exposure to cold and humid conditions led to increased intestinal enzyme activities and a shift in microbial composition, favoring the growth of rare bacterial species. These changes suggest that rare bacteria in the intestinal microbiota play a critical role in the pathology of diarrhea associated with cold-dampness trapped spleen syndrome, revealing unique survival strategies among bacterial populations under stressful conditions.

Investigation of pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm based on a "disease-syndrome-symptom-formula" association network analysis / 药学学报

Growing clinical evidence shows that Qufeng Gutong Cataplasm may exert a significant analgesic effect. However, the pharmacological characteristics and mechanisms underlying this prescription are still unclear. In the current study, a "disease-syndrome-symptom-formula" association network analysis was performed to explore the pharmacological characteristics and mechanisms of Qufeng Gutong Cataplasm against osteoarthritis (OA), neuropathic pain (NP), chronic inflammatory pain (CIP) and myofascial pain syndrome (MPS) by integrating clinical phenomics data, transcriptomics data and biological interaction network mining. As a result, the three functional modules (Qufeng Sanhan-QFSHG, Shujin Huoxue-SJHXG and Xiaozhong Zhitong-XZZTG) enriched by the drug network targets were all related to the pharmacological effects of Qufeng Gutong Cataplasm, including dispersing cold and relieving pain, activating blood and relieving pain, reducing swelling and relieving pain. In addition, the main pharmacological effects of QFSHG and XZZTG were dispelling wind and dispersing cold and dehumidifying, promoting Qi and reducing swelling and relieving pain, respectively. In terms of reversing the imbalance of "immune-inflammation-vascular axis", the main pharmacological effects of SJHXG were regulating the liver and promoting Qi, activating blood circulation and removing stasis. Mechanically, the key network targets of Qufeng Gutong Cataplasm against OA, NP, CIP and MPS may play a therapeutic role in relieving hyperalgesia and paresthesia by reversing the "neuro-endocrine-immune" imbalance system during the occurrence and progression of diseases. In conclusion, our data indicate that Qufeng Gutong Cataplasm may relieve the pain and wind-cold-dampness arthralgia syndrome related symptoms by regulating the "neuro-endocrine-immune" system, neurological and endocrine disorders and reversing the imbalance of "immunity-inflammation". The relevant results may provide a network-based evidence for clinical positioning of Qufeng Gutong Cataplasm, and offer a direction for further clinical and experimental validation.

Clinical Efficacy of Guizhi Shaoyao Zhimutang Combined with Fire Needling in Treatment of Periarthritis of Shoulder with Wind-cold-dampness Impediment Syndrome by Stimulating Pain Points and "Shoulder Three Acupoints" / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Guizhi Shaoyao Zhimutang （GZSYZM） combined with fire needling in the treatment of periarthritis of shoulder with wind-cold-dampness impediment syndrome by stimulating pain points and "shoulder three acupoints". MethodA total of 120 patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome， admitted to Hainan General Hospital from August 2020 to August 2022， were randomly divided into two groups using a random number table. The control group （60 cases） received treatment with GZSYZM for two weeks， while the observation group （60 cases） received treatment with GZSYZM combined with fire needling at pain points and "shoulder three acupoints" for two weeks. The clinical efficacy， adverse reactions， shoulder pain intensity， shoulder joint function， and levels of calcitonin gene-related peptide （CGRP）， cyclooxygenase-2 （COX-2）， interleukin （IL）-2， and IL-17 before and after treatment were compared between the two groups. ResultThe total effective rate in the observation group was 88.33% （53/60）， significantly higher than 68.33% （41/60） of the control group （χ²=7.070， P<0.01）. Compared with the results before treatment， both groups showed significant reductions in pain rating index （PRI）， visual analog scale （VAS） scores， present pain intensity （PPI）， and Simplified McGill Pain Questionnaire （SF-MPQ） total scores， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 after treatment （P<0.01）， and improved pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. Compared with the control group after treatment， the observation group showed significantly reduced PRI， VAS score， PPI， SF-MPQ total score， as well as serum levels of CGRP， COX-2， IL-2， and IL-17 （P<0.01）， and increased pain intensity， daily life abilities， joint mobility， muscle strength， and Constant-Murley score （P<0.01）. There was no significant difference in the incidence of adverse reactions between the two groups. ConclusionGZSYZM combined with fire needling at pain points and "shoulder three acupoints" can effectively reduce the levels of serum inflammatory factors and pain mediators， alleviate pain， and improve shoulder joint function in patients with periarthritis of shoulder with wind-cold-dampness impediment syndrome.

Clinical observation of warm acupuncture combined with external application of Tibetan medicine Baimai Ointment in the treatment of low-back pain with cold-dampness type / 国际中医中药杂志

Objective:To evaluate the clinical efficacy of warm acupuncture combined with external application of Tibetan medicine Baimai Ointment in the treatment of low-back pain with cold-dampness type.Methods:Randomized controlled trial. Totally 60 outpatients in Tibetan Medicine Hospital of Cuona County from May to July of 2021 were selected as the observation objects, and they were divided into two groups by random number table method, with 30 cases in each group. The control group was treated with Baimai Ointment, and the treatment group was treated with warm acupuncture and Baimai Ointment. Both groups were treated for 2 weeks and followed up for 3 months. VAS scale and Oswestry disability index (ODI) were used to evaluate the low-back pain and dysfunction, and the clinical efficacy was evaluated.Results:The VAS scores of the treatment group were lower than those in the control group immediately after treatment and at the last follow-up ( t=-18.17, -6.05, P<0.01). The ODI score of the treatment group was lower than that of the control group at the last follow-up ( t=-15.86, P<0.01). The total effective rate was 96.7% (29/30) in the treatment group and 93.3% (28/30) in the control group, without statistical significance ( χ2=0.001, P=1.000). Conclusion:Warm acupuncture combined with Tibetan medicine Baimai Ointment can effectively improve the clinical symptoms of low-back pain with cold-dampness type, improve the quality of life of patients, and the clinical effect is satisfactory.

Academician TONG Xiaolin's Understanding and Experience in Treating Severe Cases of COVID-19 / 中医杂志

This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.

Treatment of Critical COVID-19 Case Complicated with Multiple Organ Dysfunction based on “Cold-dampness Entering Ying （营）” Theory： A Case Report / 中医杂志

“Cold-dampness entering ying （营）” is the key to the worsening of cold-dampness epidemic， and is more common in the elderly or critically ill cases of cold-dampness epidemic with pathogen exuberance and healthy qi deficiency. This paper reported a case of critically ill COVID-19 combined with multiple organ dysfunction treated by integrative traditional Chinese and western medicine based on “cold-dampness entering ying” theory. The patient did not have high fever after being infected with SARS-Cov-2， but D-dimer continued to increase， and she developed multiple thrombosis throughout the body and multiple organ dysfunctions such as pulmonary embolism， edema， oliguria， and shock. The patient were with enlarged and dusky tongue， with yellow， thick and greasy coating， and sublingual blood stasis， and thready， rapid and rough pulse. All these were characteristic manifestations of “cold-dampness entering ying”， and was differentiated as cold-dampness stasis. For the treatment， symptomatic and supportive western medicine of improving heart function， anti-infection， relieving asthma， stopping cough and reducing phlegm was given as the basic therapy， and additionally， traditional Chinese medicine to open the constraint and the blocked， save from collapse and restore yang， boost qi and relieve collapse， invigorate blood and drain water was used， usually with Modified Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤加减）， which was in accordance with the pathogenesis and thus achieving good effect.

Intervention Effect of Qufeng Gutong Babu Ointment on Rat Model of Osteoarthritis with Cold-dampness Obstruction Based on PI3K/Akt Signal Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Qufeng Gutong Babu ointment （QFGT） on rats with osteoarthritis （OA） with cold-dampness obstruction， and preliminarily clarify its mechanism. MethodSD male rats were divided into 6 groups， namely， the blank group， model group， positive control drug Huoxue Zhitong ointment （HXZTG） group （1.26 cm2·d-1）， and low， medium， and high-dose QFGT group （75， 150， 300 mg·d-1）. OA model was prepared by joint cavity injection of papain and L-cysteine. On the second day of modeling， climate factors were applied to establish an animal model of combination of disease and syndrome of OA rats with cold-dampness obstruction. Standard VonFrey fiber was used to evaluate the threshold of mechanical pain. Weight bearing difference score and joint function score of both hind limbs were recorded. Hematoxylin-eosin （HE） staining and safranine fixation green staining were used to observe the pathological changes and cartilage degeneration of rat knee joint. Immunohistochemistry （IHC） was used to detect the expression of interleukin-1β （IL-1β）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， matrix metalloproteinase-9 （MMP-9）， and cathepsin K （CTSK）. Western blot was used to detect the protein expression of kinase B （Akt）， phosphorylated protein kinase B （p-Akt）， phosphatidylinositol 3-kinase （PI3K）， nuclear factor 1 （NFATc1）， MMP-9， and CTSK in T cells. ResultCompared with the normal group， the model group showed significant mechanical pain sensitivity reaction after modeling （P<0.01）， and the weight bearing difference of both hind limbs and joint function score were significantly increased （P<0.05， P<0.01）. Compared with the model group， both the high-dose QFGT group and the HXZTG group significantly reduced the mechanical pain sensitivity， weight difference， and joint function score of rats （P<0.05， P<0.01）， and the medium-dose QFGT group also improved the joint function to a certain extent， and the degeneration of the knee joint cartilage of rats was significantly reduced （P<0.05， P<0.01）. QFGT and HXZTG both inhibited the protein expression of IL-1β， IL-8， TNF-α， MMP-9， CTAK， PI3K， p-Akt， Akt， and other related proteins in articular cartilage of rats with OA to a certain extent （P<0.05， P<0.01）. ConclusionQFGT can inhibit the release of inflammatory factors and matrix metalloproteinases by inhibiting the PI3K/Akt signal pathway in articular articular cartilage of rats with OA with cold-dampness obstruction， thus ultimately weakening local cartilage degeneration and improving joint function.

Identification and validation of novel biomarkers for cold-dampness syndrome of rheumatoid arthritis based on integration of multiple bioinformatics methods / 中国中药杂志

This study aims to identify the novel biomarkers of cold-dampness syndrome(RA-Cold) of rheumatoid arthritis(RA) by gene set enrichment analysis(GSEA), weighted gene correlation network analysis(WGCNA), and clinical validation. Firstly, transcriptome sequencing was carried out for the whole blood samples from RA-Cold patients, RA patients with other traditional Chinese medicine(TCM) syndromes, and healthy volunteers. The differentially expressed gene(DEG) sets of RA-Cold were screened by comparison with the RA patients with other TCM syndromes and healthy volunteers. Then, GSEA and WGCNA were carried out to screen the key DEGs as candidate biomarkers for RA-Cold. Experimentally, the expression levels of the candidate biomarkers were determined by RT-qPCR for an independent clinical cohort(not less than 10 cases/group), and the clinical efficacy of the candidates was assessed using the receiver operating characteristic(ROC) curve. The results showed that 3 601 DEGs associated with RA-Cold were obtained, including 106 up-regulated genes and 3 495 down-regulated genes. The DEGs of RA-Cold were mainly enriched in the pathways associated with inflammation-immunity regulation, hormone regulation, substance and energy metabolism, cell function regulation, and synovial pannus formation. GSEA and WGCNA showed that recombinant proteasome 26S subunit, ATPase 2(PSMC2), which ranked in the top 50% in terms of coefficient of variation, representativeness of pathway, and biological modules, was a candidate biomarker of RA-Cold. Furthermore, the validation results based on the clinical independent sample set showed that the F1 value, specificity, accuracy, and precision of PSMC2 for RA-Cold were 70.3%, 61.9%, 64.5%, and 81.3%, respectively, and the area under the curve(AUC) value was 0.96. In summary, this study employed the "GSEA-WGCNA-validation" integrated strategy to identify novel biomarkers of RA-Cold, which helped to improve the TCM clinical diagnosis and treatment of core syndromes in RA and provided an experimental basis for TCM syndrome differentiation.

[Identification and validation of novel biomarkers for cold-dampness syndrome of rheumatoid arthritis based on integration of multiple bioinformatics methods].

This study aims to identify the novel biomarkers of cold-dampness syndrome(RA-Cold) of rheumatoid arthritis(RA) by gene set enrichment analysis(GSEA), weighted gene correlation network analysis(WGCNA), and clinical validation. Firstly, transcriptome sequencing was carried out for the whole blood samples from RA-Cold patients, RA patients with other traditional Chinese medicine(TCM) syndromes, and healthy volunteers. The differentially expressed gene(DEG) sets of RA-Cold were screened by comparison with the RA patients with other TCM syndromes and healthy volunteers. Then, GSEA and WGCNA were carried out to screen the key DEGs as candidate biomarkers for RA-Cold. Experimentally, the expression levels of the candidate biomarkers were determined by RT-qPCR for an independent clinical cohort(not less than 10 cases/group), and the clinical efficacy of the candidates was assessed using the receiver operating characteristic(ROC) curve. The results showed that 3 601 DEGs associated with RA-Cold were obtained, including 106 up-regulated genes and 3 495 down-regulated genes. The DEGs of RA-Cold were mainly enriched in the pathways associated with inflammation-immunity regulation, hormone regulation, substance and energy metabolism, cell function regulation, and synovial pannus formation. GSEA and WGCNA showed that recombinant proteasome 26S subunit, ATPase 2(PSMC2), which ranked in the top 50% in terms of coefficient of variation, representativeness of pathway, and biological modules, was a candidate biomarker of RA-Cold. Furthermore, the validation results based on the clinical independent sample set showed that the F1 value, specificity, accuracy, and precision of PSMC2 for RA-Cold were 70.3%, 61.9%, 64.5%, and 81.3%, respectively, and the area under the curve(AUC) value was 0.96. In summary, this study employed the "GSEA-WGCNA-validation" integrated strategy to identify novel biomarkers of RA-Cold, which helped to improve the TCM clinical diagnosis and treatment of core syndromes in RA and provided an experimental basis for TCM syndrome differentiation.

[Mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis with syndrome of internal obstruction and cold-dampness and compatibility principles based on "disease-syndrome-formula" association network].

This study aims to explore the mechanism of Tianhe Zhuifeng Ointment in treating rheumatoid arthritis(RA) with syndrome of internal obstruction and cold-dampness and the compatibility characteristics based on the "disease-syndrome-formula" association network. A gene set associated with the clinical symptoms of RA was collected from Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine v2.0(TCMIP v2.0). The different expression gene set of RA with syndrome of internal obstruction and cold-dampness was screened out by transcriptomic expression profile detection and bioinformatics data mining of the comparison of RA patients with syndrome of internal obstruction and cold-dampness and healthy volunteers. The chemical composition information of 35 Chinese medicines from Tianhe Zhuifeng Ointment was collected from TCMIP v2.0 and Traditional Chinese Medicine Bank(TCMBank). The candidate targets were predicted based on the similarity principle of compounds structure. The interactive network of "related gene of RA with syndrome of internal obstruction and cold-dampness-candidate target of Tianhe Zhuifeng Ointment" was constructed. The core network targets were screened out by topological characteristics of calculating network, and the functional exploration was carried out based on Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome Pathway Database. The compatibility mechanisms of various efficacy groups of Tianhe Zhuifeng Ointment were further explored. The results showed that the candidate targets of Tianhe Zhuifeng Ointment were mainly involved into the modules of "immune-inflammation" regulation, nervous system function, cell function, and substance and energy metabolism, etc. The mechanisms of various efficacy groups emphasized on different aspects. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, and the group of pungent analgesia regulated "immune-inflammation" system by warming meridians and dissipating cold. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated "immune-inflammation" system by activating blood and dredging channels. The group of dispelling wind and removing dampness-dredging channels and activating collaterals, the group of extinguishing wind and stopping convulsions, the group of activating blood and resolving stasis, the group of strengthening sinews and bones, and the group of clearing heat and draining water affected the nervous system by invigorating Qi-blood and benefiting spirit. The group of dispelling wind and removing dampness-dredging channels and activating collaterals and the group of extinguishing wind and stopping convulsions regulated cell function and substance and energy metabolism by dispelling wind and eliminating cold-dampness. The group of activating blood and resolving stasis and the group of strengthening sinews and bones regulated the cell function and substance and energy metabolism by activating blood and strengthening sinews and bones. The results showed that Tianhe Zhuifeng Ointment exerted the comprehensive efficacy of dispelling wind, removing dampness, activating blood, removing stasis, warming meridians, dredging channels, and strengthening sinews and bones through adjusting the imbalance of "immune-inflammation", regulating nervous system, cell function, and interfering with substance and energy metabolism, thus improving the syndrome of internal obstruction and cold-dampness. The findings of this study laid foundations for clarifying the therapeutic characteristics and clinical orientation of Tianhe Zhuifeng Ointment.

[Warming acupuncture combined with "three steps and seven methods" of tuina for chronic nonspecific low back pain of yang deficiency and cold-dampness blockage: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy and possible mechanism of warming acupuncture combined with "three steps and seven methods" of tuina and simple "three steps and seven methods" of tuina in treatment of chronic nonspecific low back pain (NLBP) of yang deficiency and cold-dampness blockage. METHODS: A total of 138 patients were randomized into an observation group (69 cases, 5 cases dropped off) and a control group (69 cases, 7 cases dropped off). In the control group, "three steps and seven methods" of tuina was applied. On the basis of the treatment in the control group, warming acupuncture was applied at Shenshu (BL 23), Yaoyangguan (GV 3), Mingmen (GV 4), Weizhong (BL 40) and ashi points. The treatment was given once a day, 6 times a week for 3 weeks in both groups. Before and after treatment, the short form of McGill pain questionnaire (SF-MPQ) score, Oswestry disability index (ODI) score, finger-to-floor distance (FFD), Schober test distance, fear-avoidance beliefs questionnaire (FABQ) score and yang deficiency and cold-dampness blockage score were observed, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6 and thromboxane B2 (TXB2) were detected in both groups. The recurrence rate was evaluated in follow-up of 6 months after treatment. RESULTS: After treatment, the scores of PRI, PPI, VAS, ODI, FABQ and FFD, yang deficiency and cold-dampness blockage scores were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01); the Schober test distances were increased compared before treatment in both groups (P<0.01), and that in the observation group was larger than the control group (P<0.01). After treatment, the serum levels of TNF-α, IL-1ß, IL-6 and TXB2 were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). In follow-up, the recurrence rate was 12.8% (6/47) in the observation group, which was lower than 34.3% (12/35) in the control group (P<0.05). CONCLUSION: Warming acupuncture combined with "three steps and seven methods" of tuina can effectively alleviate pain in patients with chronic NLBP of yang deficiency and cold-dampness blockage, improve activity and dysfunction of waist, the clinical efficacy is superior to simple "three steps and seven methods" of tuina, its mechanism may be relate to the inhibition of inflammatory reaction.

Warming acupuncture combined with "three steps and seven methods" of tuina for chronic nonspecific low back pain of yang deficiency and cold-dampness blockage: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy and possible mechanism of warming acupuncture combined with "three steps and seven methods" of tuina and simple "three steps and seven methods" of tuina in treatment of chronic nonspecific low back pain (NLBP) of yang deficiency and cold-dampness blockage.@*METHODS@#A total of 138 patients were randomized into an observation group (69 cases, 5 cases dropped off) and a control group (69 cases, 7 cases dropped off). In the control group, "three steps and seven methods" of tuina was applied. On the basis of the treatment in the control group, warming acupuncture was applied at Shenshu (BL 23), Yaoyangguan (GV 3), Mingmen (GV 4), Weizhong (BL 40) and ashi points. The treatment was given once a day, 6 times a week for 3 weeks in both groups. Before and after treatment, the short form of McGill pain questionnaire (SF-MPQ) score, Oswestry disability index (ODI) score, finger-to-floor distance (FFD), Schober test distance, fear-avoidance beliefs questionnaire (FABQ) score and yang deficiency and cold-dampness blockage score were observed, the serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and thromboxane B2 (TXB2) were detected in both groups. The recurrence rate was evaluated in follow-up of 6 months after treatment.@*RESULTS@#After treatment, the scores of PRI, PPI, VAS, ODI, FABQ and FFD, yang deficiency and cold-dampness blockage scores were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01); the Schober test distances were increased compared before treatment in both groups (P<0.01), and that in the observation group was larger than the control group (P<0.01). After treatment, the serum levels of TNF-α, IL-1β, IL-6 and TXB2 were decreased compared before treatment in both groups (P<0.01), and those in the observation group were lower than the control group (P<0.01). In follow-up, the recurrence rate was 12.8% (6/47) in the observation group, which was lower than 34.3% (12/35) in the control group (P<0.05).@*CONCLUSION@#Warming acupuncture combined with "three steps and seven methods" of tuina can effectively alleviate pain in patients with chronic NLBP of yang deficiency and cold-dampness blockage, improve activity and dysfunction of waist, the clinical efficacy is superior to simple "three steps and seven methods" of tuina, its mechanism may be relate to the inhibition of inflammatory reaction.

Discussion on Treatment of Diarrhea of Intestinal Dampness-heat Syndrome and of Cold-dampness Disturbing Spleen Syndrome with Different Methods： Based on Intestinal Microbiota Function / 中国实验方剂学杂志

ObjectiveTo study the changes of microbiota in different intestinal niches in the instance of diarrhea with intestinal dampness-heat syndrome and cold-dampness disturbing spleen syndrome， so as to provide objective evidence for treating diarrhea with different methods from the perspective of intestinal flora. MethodThe 16S rRNA gene high-throughput sequencing data of model mice with diarrhea of the two syndromes and the model mice after prescription intervention were retrieved from National Center for Biotechnology Information （NCBI）， and the intestinal dominant bacteria and microbial functions were compared among groups. Spearman's correlation coefficient among the microorganisms in each group was calculated and the co-occurrence networks of intestinal microbiota were constructed to study the interaction of the microbiota. ResultThe microbiota imbalance in intestinal contents of mice with diarrhea of intestinal dampness-heat syndrome was characterized by the enrichment of Muribaculum and Aerococcus， while the imbalance in intestinal mucosa was manifested by the enrichment of Gram-negative Neisseria， Capnocytophaga， and Prevotella （P<0.05）. However， after the treatment with Gegen Qinliantang， the microbiota in two distinct ecosystems was characterized by the enrichment of Lactobacillus and the abundance of Streptococcus in intestinal mucosa was increased. The microbiota imbalance in intestinal contents of diarrhea with cold-dampness disturbing spleen syndrome was characterized by the enrichment of Lactobacillus （P<0.01） and Clostridium sensu stricto 1， while the intestinal mucosa was dominated by the increase of Candidatus arthromitus and Enterobacter. However， after the treatment with Huoxiang Zhengqi powder， the intestinal contents were characterized by Lactobacillus enrichment， while the intestinal mucosal flora was featured by the enrichment of C. arthromitus， Pseudomonas， and Bacillus. Overall， the contribution of dominant bacteria in intestinal mucosa to the difference was higher than that in intestinal contents， and more dominant bacteria in the intestinal mucosa interacted with other bacteria. ConclusionMicrobiota imbalance is different for diarrhea of different syndromes， and the therapeutic effects of corresponding prescriptions are also different. In addition， the microbiota imbalance has different characteristics between intestinal niches for mice with diarrhea of the same syndrome. Therefore， intestinal flora may be one of the biological bases for exploring the characteristics of "treating the diarrhea with different methods" in Chinese medicine.

Traditional Chinese Medicine and Western Medicine Share Similar Philosophical Approaches to Fight COVID-19.

Though disciplines in the same field, modern medicine (Western medicine) and traditional medicine (Traditional Chinese medicine, TCM) have been viewed as two distinct and divergent fields of medicine and thus differ greatly in their ways of diagnosing, treating, and preventing disease. In brief, Western medicine is primarily an evidence (laboratory)-based science, whereas TCM is more of a healing art based on the theory of Yin and Yang and the five elements in the human body. Therefore, whether TCM and Western medicine could use similar philosophical approaches to treat disease remains unclear. It is well-known that vitamin D enhances immune function and reduces the spread of some viruses. Indeed, recent evidence shows that the blood calcium level is strongly associated with COVID-19 severity, and vitamin D supplementation has shown favorable effects in viral infections. According to TCM theory, the pathogenesis of COVID-19 is closely associated with cold-dampness, an etiological factor in TCM. Cold-dampness could be attenuated by sun exposure and Wenyang herbs, both of which can restore the vitamin D level in the blood in Western medicine. Therefore, TCM and Western medicine could share similar philosophical methods to fight COVID-19 and understanding their philosophical theories could achieve the maximum benefits for treatment of COVID-19 and other diseases.

Zhuifeng Tougu capsules improve rheumatoid arthritis symptoms in rats by regulating the toll-like receptor 2/4-nuclear factor kappa-B signaling pathway.

OBJECTIVE: To investigate the efficacy of Zhuifeng tougu capsules (, ZFTG) in the treatment of rheumatoid arthritis (RA) in rats and study its mechanism, focusing on the toll-like receptor 2/4-nuclear factor kappa-B (TLR2/4-NF-κB) signaling pathway. METHODS: Type Ⅱ collagen and an artificial climate box were used to construct the rat model of collagen-induced arthritis with wind-cold-dampness arthralgia syndrome. The rats were divided randomly into a control group, wind-cold-dampness syndrome model group, and high-, medium-, and low-dose ZFTG groups. The methotrexate (MTX) control group was treated with the corresponding drug intervention for 28 d. The joint temperature, pain threshold, joint swelling degree, and arthritis index (AI) score were measured. The production of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factors (RFs) in the blood was detected by enzyme-linked immunosorbent assay. The protein expression of TLR2, TLR4, and NF-κB in synovial tissues was detected by Western blotting, and the mRNA expression of TLR2, TLR4, and NF-κB was detected by real-time polymerase chain reaction. RESULTS: Compared with the model group, the joint temperature in each treatment group, the MTX control group, and MTX group recovered, the degree of foot swelling, pain threshold, AI score decreased, serum CRP, ESR, RF level and the levels of TLR2, TLR4, and NF-κB in synovial tissue were decreased (P < 0.05). Among them, the curative effect in the medium-dose and MTX groups was more evident (P < 0.01). CONCLUSION: ZFTG has a significant effect on RA in rats, and its mechanism may involve regulating CRP levels, the ESR, and RFs via the TLR2/4-NF-κB signaling pathway.

Understanding COVID-19 in Wuhan From the Perspective of Cold-Dampness: Clinical Evidences and Mechanisms.

Traditional Chinese medicine (TCM) has played a significant role in the treatment of coronavirus disease 2019 (COVID-19) in Wuhan City. During the epidemic, Academician Tong Xiaolin suggested a close association of COVID-19 with cold-dampness, an etiological factor in TCM, by summarizing the characteristics of the COVID-19 patients in Wuhan. and the theory of Cold-dampness Plague was proposed. Based on the Cold-dampness Plague theory, a series of TCM drugs, such as Huoxiang Zhengqi Dropping Pills, Lianhua Qingwen Granules Hanshiyi Formula, and Tongzhi Granule were developed for the different stages, namely mild, moderate, severe, recovery, of the COVID-19. In addition, clinical evidences were obtained through randomized clinical trials or retrospective cohort studies. The Anti-SARS-CoV-2 mechanism of the TCM prescriptions were then summarized from the four aspects: targeting the ACE2 and 3CLPro, targeting cytokines, targeting acute immune responses to SARS-CoV-2, and targeting pulmonary fibrosis. Despite the clinical efficacy and therapeutic pharmacology speculation, more studies such as large-scale randomized clinical trials, cell and animal experiments are needed to further verify the theory of the Cold-dampness Plague in COVID-19 patients.

Clinical observation on the time-effect relationship of moxibustion for primary dysmenorrhea due to stagnation and congelation of cold-damp / 针灸推拿医学（英文版）

Objective: To observe the time-effect relationship of moxibustion for primary dysmenorrhea (PD) due to stagnation and congelation of cold-damp, thus explore the optimal choice of moxibustion duration, and provide evidence for achieving satisfactory efficacy in moxibustion treatment. Methods: A total of 90 patients with PD due to stagnatin and congelation of cold-damp were divided into three groups by the random number table method, with 30 cases in each group. All the patients in the three groups were given moxibustion treatment at Guanyuan (CV 4), 20 min in group A, 40 min in group B and 60 min in group C. The changes in the pain measurement score in the three groups were observed after treatment. Results: After treatment, there were significant differences in the clinical efficacy among the three groups (P<0.05); the clinical efficacy was better in group B and group C than that in group A (P<0.05), and that in group B was better than that in group C (P<0.05). Besides, the pain measurement score changed significantly after treatment in the three groups (all P<0.05), and the between-group differences were also statistically significant (P<0.05); the pain measurement scores in group B and group C were lower than that in group A (P<0.05), and that in group B was lower than that in group C (P<0.05). Conclusion: Given the same stimulating frequency and intervention time of moxibustion, 40-minute duration demonstrates relatively better efficacy for PD due to stagnation and congelation of cold-damp.

Clinical Observation on Orthopedics No.1 Prescription Combined with Celecoxib in Treating Knee Osteoarthritis with Middle Stage of Cold-dampness Syndrome / 中国实验方剂学杂志

Objective:To study the clinical efficacy of orthopedics No.1 prescription combined with celecoxib in the treatment of knee osteoarthritis （KOA） with middle stage of cold-dampness syndrome and investigate its effect on serum cytokines levels. Method:The 72 patients were randomly divided into control group and observation group， with 36 cases each. Patients in both groups were given basic treatment with oral celecoxib capsules （0.2 g/ time， 1 time/day）. On the basis of western medicine treatment， patients in observation group were treated with orthopedics No.1 prescription decoction-free granules by fumigation， 1 bag/time， 1 time/day， 5 times/week. Both groups received treatment for 4 weeks. The visual analog pain score （VAS）， American knee society knee score （KSS）， serum interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， and transforming growth factor-<italic>β</italic>₁（TGF-<italic>β</italic>₁） levels were observed before and after treatment， and their clinical efficacy was evaluated. Result:After treatment， VAS score significantly decreased in both groups （<italic>P</italic><0.01）， and KSS score significantly increased （<italic>P</italic><0.01）， with better clinical effect in observation group. After treatment， serum IL-1<italic>β</italic> and TNF-<italic>α</italic> levels decreased significantly in both groups （<italic>P</italic><0.01）， and the levels in observation group were lower than those in control group after treatment （<italic>P</italic><0.05）. TGF<italic>-β</italic>₁content was significantly higher than that before treatment in two groups （<italic>P</italic><0.01）. Conclusion:Orthopedics No.1 prescription combined with celecoxib for the treatment of KOA with middle stage of cold-dampness syndrome can effectively relieve the clinical symptoms of patients with KOA， improve joint function， improve quality of life， reduce the contents of inflammatory factors IL-1<italic>β</italic> and TNF-<italic>α</italic> in serum， and increase the expression of TGF-<italic>β</italic>₁ level.