Based on the thinking of programmatization and proceduralization， this study integrated traditional Chinese medicine （TCM） classic theories with modern knowledge expression technologies to construct a "formula-symptom" syndrome differentiation thinking model centered on "symptom clustering-main syndrome screening-formula adaptation"， and explored the standardization and intelligentization path of TCM syndrome differentiation and treatment. By establishing the mapping relationship model between formulas and syndromes including quantitative weight analysis of chief， deputy， assistant and envoy medicines， designing the logical hierarchical structure of formula-syndrome decision tree （application of three-level decision tree and fuzzy logic）， and formulating the procedural design of four diagnostic methods （structured collection， correlation model， and dynamic correction mechanism）， the standardization and visualization of the syndrome differentiation process are realized. This model can be transformed into the core data set for artificial intelligence training. Through ternary knowledge graph and machine learning algorithms， it can improve the repeatability of syndrome differentiation and the efficiency of diagnosis and treatment， and implement the strategy of "group model + individual modification" to balance the conflict between quantification and individualization. The core value of this model lies in promoting the objectification and precision development of TCM syndrome differentiation and treatment through the integration of traditional syndrome differentiation thinking and modern system science.

ObjectiveTo investigate the possible mechanism of Jishe Qushi Capsule （脊蛇祛湿胶囊， JQC） in treating rheumatoid arthritis （RA） from the perspective of macrophage polarization mediated by neutrophil extracellular traps （NETs）. MethodsTwenty-four female SD rats were randomly divided into four groups， blank control group， model group， JQC group， and peptidylarginine deiminase 4 （PAD4） inhibitor group with 6 rats in each group. All groups but the blank control group were subjected to the induction of collagen-induced arthritis （CIA）. After successful model establishment， rats in the JQC group received intragastric administration of JQC 1.47 g/kg daily； rats in the PAD4 inhibitor group received intraperitoneal injections of the PAD4 inhibitor 4 mg/kg weekly. Rats in the blank， model， and PAD4 inhibitor groups received 2 ml of pure water daily by gavage. All treatments lasted 4 weeks. Joint lesions of each group were assessed on day 7， 14， 21， 28， and 35 after model establishment， and arthritis index （AI） scores were recorded. At 24 h after the final administration， histopathology of knee joints， including HE staining， safranin O-fast green staining， and TRAP staining， was performed. Flow cytometry was used to detect the counts of M1 and M2 macrophages in peripheral blood. ELISA was used to determine serum levels of TRACP， NETs， TNF-α， IL-1β， and iNOS. Western Blotting and qRT-PCR were used to measure MPO， NE， RANKL， OPG， and p65 protein and mRNA expression in knee cartilage tissue. ResultsCompared with the blank control group， the model group showed increased AI scores （P＜0.05）， marked synovial inflammatory infiltration， angiogenesis， and bone-cartilage destruction， increased TRAP-positive osteoclasts， increased M1 macrophages and decreased M2 macrophages， elevated serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， elevated MPO， NE， RANKL， and p65 protein/mRNA expression and decreased OPG protein/mRNA expression in knee cartilage tissue （P＜0.05）. Compared with the model group， the JQC group exhibited improved synovial inflammation， angiogenesis， and bone-cartilage damage， reduced AI scores on day 21， 28， and 35， decreased osteoclast counts， decreased M1 macrophages and increased M2 macrophages， reduced serum TRACP， NETs， TNF-α， IL-1β， and iNOS （P＜0.05）， decreased MPO， NE， RANKL， and p65 protein/mRNA expression and increased OPG expression （P＜0.05）. Compared with the PAD4 inhibitor group， the JQC group showed significantly lower AI scores， reduced M1 macrophages， increased M2 macrophages （P＜0.05）， reduced serum TRACP， TNF-α， IL-1β， and iNOS， decreased MPO， RANKL， and p65 expression， and increased OPG levels （P＜0.05）. ConclusionThe therapeutic mechanism of JQC for RA may involve inhibition of NETs formation， downregulation of the RANKL/NF-κB signaling pathway， and regulation of macrophage M1/M2 polarization imbalance， thereby suppressing osteoclastogenesis and inflammatory bone destruction.

ObjectiveTo observe the effects of Yangjing Zhongyutang （YJZYT） on mitochondrial biogenesis and oxidative stress damage mediated by the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor gamma coactivator-1alpha （PGC-1α） signaling pathway in cyclophosphamide （CTX）-induced rats with diminished ovarian reserve （DOR）， and to explore its mechanism in improving ovarian reserve function and follicular development. MethodsForty-two 8-week-old female SD rats with normal estrous cycles were randomly divided into a blank control group （n=7） and a model group （n=35）. Rats in the model group received a single intraperitoneal injection of CTX （90 mg·kg^-1） to establish the DOR model. After modeling， estrous cycles were monitored for 7 consecutive days， and model success was confirmed based on criteria for estrous cycle disruption. After successful modeling， rats were divided into groups for intervention： estradiol valerate group （0.09 mg·kg^-1）， and YJZYT high-， medium-， and low-dose groups （19.98， 9.99， 5.00 g·kg^-1）. The blank control group and model group were given an equal volume of distilled water by gavage. All groups received daily gavage once for 4 consecutive weeks. The general state， body weight， and ovarian wet weight of rats were observed and recorded， and the ovarian organ index was calculated. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， anti-Müllerian hormone （AMH）， superoxide dismutase （SOD）， and glutathione peroxidase （GSH-Px）. Hematoxylin-eosin （HE） staining was performed to observe ovarian histomorphological changes and follicular development status. Immunofluorescence was used to detect reactive oxygen species （ROS） expression levels. Colorimetric assays were employed to measure adenosine triphosphate （ATP） and malondialdehyde （MDA） content in ovarian tissues. Quantitative Real-time polymerase chain reaction （Real-time PCR） was used to detect mitochondrial DNA （mtDNA） copy number and the mRNA expression levels of key genes including SIRT1， PGC-1α， nuclear respiratory factor 1 （NRF1）， and mitochondrial transcription factor A （TFAM）. Western blot was performed to detect the protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM. ResultsCompared with the blank group， rats in the model group exhibited disrupted estrous cycles， obviously reduced body weight， and decreased ovarian index （P<0.05）. Ovarian histopathology revealed cortical thinning， loose structure， and a significant reduction in both primordial and growing follicles （P<0.01）. Serum FSH and LH levels were significantly elevated （P<0.01）， while E₂ and AMH levels were obviously reduced （P<0.05， P<0.01）. ATP content and mtDNA copy number decreased in ovarian tissue （P<0.01）， ROS expression increased， MDA levels rose， while SOD and GSH-Px activities obviously decreased （P<0.05， P<0.01）， mRNA and protein expression levels of SIRT1， PGC-1α， NRF1， and TFAM were obviously downregulated （P<0.05， P<0.01）. After treatment， compared with the model group， body weight and ovarian index obviously recovered in rats administered various doses of YJZYT （P<0.05）， serum E₂ and AMH levels increased， while FSH and LH levels obviously decreased （P<0.05， P<0.01）， ovarian tissue ATP content and mtDNA copy number were up-regulated， ROS and MDA levels decreased， and antioxidant enzymes SOD and GSH-Px activity obviously increased （P<0.05， P<0.01）， Gene and protein expression levels related to the SIRT1/PGC-1α /NRF1/TFAM signaling pathway were obviously up-regulated compared to the model group （P<0.05， P<0.01）， HE staining revealed that ovarian structure gradually recovered to integrity in all treatment groups， with a obviously increase in the number of primordial and growing follicles （P<0.05， P<0.01）. Granulosa cells were neatly arranged， indicating marked improvement in ovarian function. ConclusionYJZYT may improve ovarian function and follicular development in rats with diminished ovarian reserve by activating the SIRT1/PGC-1α signaling pathway， promoting mitochondrial biogenesis， enhancing mitochondrial function， and alleviating oxidative stress damage.

ObjectiveTo investigate the mechanisms of Runmu Dihuang decoction （RMDHD） in treating perimenopausal dry eye with liver-kidney Yin deficiency syndrome based on the silent information regulator 3 （SIRT3）/hypoxia-inducible factor-1α （HIF-1α）/nuclear factor-κB （NF-κB） signaling pathway. MethodsSixty female Sprague-Dawley rats were randomly divided into six groups （n=10 per group）： Sham operation group， model group， sodium hyaluronate eye drop group， and low-， medium-， and high-dose RMDHD groups （5.625， 11.25， 22.50 g·kg^-1）. Except for the sham operation group， all rats underwent bilateral ovariectomy and were administered 0.1% benzalkonium chloride eye drops combined with long-term chronic irritation to establish a perimenopausal dry eye model with liver-kidney Yin deficiency syndrome. Drug administration began in the 11th week after modeling and continued for 21 days. General conditions， screen-grip test scores， tear secretion volume， tear film breakup time （TFBUT）， and corneal fluorescein staining were recorded. Serum levels of reactive oxygen species （ROS）， follicle-stimulating hormone （FSH）， estradiol （E₂）， and progesterone （PROG） were measured by enzyme-linked immunosorbent assay （ELISA）. Pathological changes in the lacrimal glands， corneas， and uteri were observed using hematoxylin-eosin （HE） staining. Protein expression levels of SIRT3， HIF-1α， phosphorylated NF-κB p65 （p-NF-κB p65）， and total NF-κB p65 in the lacrimal glands were detected by Western blot. The expression of inflammatory cytokines interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the lacrimal glands was assessed by immunohistochemistry （IHC）. ResultsAfter model establishment， no significant differences were observed among the groups except the sham operation group. Compared with the sham operation group， the other groups exhibited slowed movement， dull responses， increased irritability， reduced body weight， elevated rectal temperature， decreased screen-grip test scores， reduced tear secretion， and significantly shortened TFBUT （P<0.05）. After treatment， compared with the model group， the sodium hyaluronate eye drop group and all RMDHD groups showed improved general conditions， significantly increased tear secretion （P<0.05）， prolonged TFBUT （P<0.05）， and elevated screen-grip test scores （P<0.05）. Serum ROS and FSH levels were significantly decreased， while E₂ and PROG levels were significantly increased （P<0.05）. Pathological damage to the cornea， lacrimal glands， and uterus was ameliorated. In addition， protein expression levels of SIRT3 and HIF-1α in the lacrimal glands were significantly upregulated （P<0.05）， whereas the expression of p-NF-κB p65， IL-1β， and TNF-α was significantly downregulated （P<0.05）. ConclusionRMDHD increases tear secretion and TFBUT， improves lacrimal gland and corneal injury， and alleviates dry eye symptoms in a perimenopausal dry eye rat model with liver-kidney Yin deficiency syndrome. The underlying mechanism may be related to regulation of the SIRT3/HIF-1α/NF-κB signaling pathway， inhibition of oxidative stress and inflammatory responses， and reduction of ocular surface tissue damage.

Polycystic ovary syndrome （PCOS） is one of the most prevalent gynecological diseases， and its incidence is increasing year by year， seriously affecting the physical and mental health of female patients. The pathogenesis of this disease is complex and has not been fully clarified. At present， PCOS is mainly treated by Western medicine， which， however， has poor efficacy and induces various adverse reactions. Therefore， developing safe and effective therapies has become a difficult problem that needs to be solved. Studies have confirmed that traditional Chinese medicine （TCM） can regulate phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， mitogen-activated protein kinase/extracellular signal-regulated kinase （MAPK/ERK）， Toll-like receptor 4/nuclear factor-κB （TLR4/NF-κB）， transforming growth factor-β （TGF-β）/Smads， secreted glycoprotein/β-catenin （Wnt/β-catenin）， adenosine monophosphate-activated protein kinase （AMPK）， and advanced glycation endproduct/receptor for advanced glycation endproducts （AGE/RAGE） signaling pathways to ameliorate insulin resistance， inhibit inflammation and oxidative stress， regulate endocrine hormone disorders， and intervene in apoptosis and autophagy， thus alleviating the symptoms， slowing down the disease progression， and improving the ovarian function. The treatment of PCOS with TCM has demonstrated definite effects and high safety. Therefore， exploring this disease from cellular and molecular perspectives can provide a theoretical basis for its clinical treatment and new drug development. However， there is a lack of systematic reviews on the modulation of relevant signaling pathways by TCM in the treatment of PCOS. This article reviews the research progress in the treatment of PCOS with the active ingredients and compound prescriptions of TCM by regulating relevant signaling pathways in recent years， with the aim of providing evidence to support the promotion of TCM for treating PCOS in the future.

Objective To establish an HPLC method to determine the concentration of inositol nicotinate（IN） in rat skin, and study the pharmacokinetic characteristics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats. Methods HPLC method was used to establish a simple and rapid analytical method for the determination of IN concentration in the skin of rats at different time points after administration. The established method was used to study the pharmacokinetics of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats, and the pharmacokinetic parameters were fitted with DAS software. Results The linearity of the analytical method was good in the concentration range of 0.25-20 μg/ml, the quantitative limit was 0.25 μg/ml, and the average recovery rate was 96.18%. The pharmacokinetic parameters of IN after transdermal administration of heparin sodium inositol nicotinate cream in rats were as follows: t_1/2 was （4.555±2.054） h, T_max was （6±0）h, C_max was （16.929±2.153）mg/L, AUC_0−t was （150.665±16.568） mg·h /L ,AUC_0−∞ was （161.074±23.917） mg·h /L, MRT_（0−t） was （9.044±0.618）h, MRT_{（0−∞）} was （10.444±1.91） h, CLz/F was （0.19±0.03） L/（h·kg）, and Vz/F was （1.19±0.437） L/（h·kg）. Conclusion IN could quickly penetrate the skin and accumulate in the skin for a long time, which was beneficial to the pharmacological action of drugs on the lesion site for a long time. The method is simple, rapid, specific and reproducible, which could be successfully applied to the pharmacokinetic study of IN after transdermal administration in rats.

ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.