1.Comparison of Efficacy and Mechanism in Warming Yang and Dispersing Cold of Aconiti Radix Lateralis Praeparata Processed by ZHANG Zhongjing's Method and Pharmacopoeia Method
Mingjie JIAO ; Qian CHEN ; Shuyu YAN ; Yiyan SONG ; Jia ZHANG ; Fei LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):207-217
ObjectiveTo investigate the therapeutic effects and mechanism of decoctions from four kinds of processed products of Aconiti Radix Lateralis Praeparata(ARLP) in deficiency-cold syndrome. MethodsA total of 36 SD rats were randomly divided into the control group, model group, Shengfupian(SFP) group, Paofuzi(PFZ) group, Heishunpian(HSP) group and Paofupian(PFP) group with 6 rats in each group. Except for the control group, rats in other groups were administered hydrocortisone sodium succinate via intramuscular injection to induce a cold deficiency syndrome model. After 14 consecutive days, each ARLP decoction pieces was administered via continuous gastric lavage at a dose of 12 g·kg-1·d-1 for 7 d, while the control and model groups received an equivalent volume of physiological saline. After the end of administration, body weight, spleen weight and thymus weight were measured for calculating the spleen and thymus indexes. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of adrenal tissue. The fully automatic biochemistry analyzer was used to measure the total cholesterol(TC), triglyceride(TG), lactic dehydrogenase(LDH) and lactate(LAC) levels in serum. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the contents of 17-hydroxycorticosteroid(17-OHCS), cortisol(CORT), triiodothyronine(T3), thyroxine(T4), thyrotropin(TSH), immunoglobulin(Ig) M, IgG, cyclic adenosine monophosphate(cAMP) and cyclic guanosine monophosphate(cGMP). Western blot was used to measure the protein expression levels of protein kinase A(PKA), cAMP response element-binding protein(CREB), silent information regulator 1(Sirt1) and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α). And high performance liquid chromatography(HPLC) was used to determine the content of major alkaloids, followed by Pearson correlation analysis with pharmacodynamic indicators. ResultsAfter modeling, compare with the control group, the model rats exhibited symptoms such as lethargy and loose stools, mild abnormalities were observed in adrenal tissue structure, and both spleen and thymus indices were significantly reduced(P<0.01). Thyroid, adrenal and immune system functions were suppressed, with decreased serum cAMP level and significantly elevated cGMP level(P<0.01). Compared with the model group, the adrenal injury by hydrocortisone sodium succinate were repaired and the spleen index were increased significantly in all four ARLP groups(P<0.05, P<0.01). The thymus index in SFP and PFZ groups were increased significantly(P<0.05). The contents of T3, TSH, 17-OHCS and CORT were increased significantly in SFP and PFZ groups(P<0.05). In addition, the content of IgG in SFP, PFZ and PFP groups were increased significantly(P<0.01), while the content of IgM in PFZ and HSP groups were also increased significantly(P<0.05). Regarding the cyclic nucleotide system, PFZ significantly elevated cAMP level while reducing cGMP level(P<0.05), exhibiting the most pronounced effect among the four decoction pieces. For energy metabolism indicators, PFZ significantly improved abnormal markers including TC, TG, LDH, and LAC(P<0.05). HSP showed marked improvement effects on TG, LDH, and LAC(P<0.05). Both PFZ and SFP significantly elevated the expression levels of PKA, CREB, Sirt1, and PGC-1α proteins(P<0.01). Additionally, the diester alkaloids in ARLP showed a strong positive correlation with TG, IgG, and CORT, a strong negative correlation with LAC, a moderate positive correlation with T4, and moderate negative correlations with cAMP and spleen index. Monomeric alkaloids showed strong positive correlations with TG and IgG, strong negative correlations with LAC, moderate positive correlations with CORT and T4, and moderate negative correlations with cAMP and spleen index. However, the content of water-soluble alkaloids showed strong positive correlations with TC, LDH, 17-OHCS, T3, TSH, and thymus index, moderate positive correlations with cAMP, CORT, T4, and spleen index, and moderate negative correlation with cGMP. ConclusionAmong different processed ARLP decoction pieces, PFZ processed according to ZHANG Zhongjing's method exhibits the most potent warming and cold-dispelling effects. Its pharmacological actions are mediated through regulating the thyroid, adrenal, immune, cyclic nucleotide systems, and material-energy metabolism pathways. Among these, water-soluble alkaloids show strong or moderate correlations with more indicators of deficiency-cold syndrome and exhibit the highest content in PFZ. Therefore, PFZ processed according to ZHANG Zhongjing's method may exert its warming and cold-dispelling effects through water-soluble alkaloids.
2.The Regulatory Effects and Mechanisms of Piezo1 Channel on Chondrocytes and Bone Metabolic Dysregulation in Osteoarthritis
Yan LI ; Tao LIU ; Yu-Biao GU ; Hui-Qing TIAN ; Lei ZHANG ; Bi-Hui BAI ; Zhi-Jun HE ; Wen CHEN ; Jin-Peng LI ; Fei LI
Progress in Biochemistry and Biophysics 2026;53(3):564-576
Osteoarthritis (OA), a highly prevalent degenerative joint disease worldwide, is defined by articular cartilage degradation, abnormal bone remodeling, and persistent chronic inflammation. It severely compromises patients’ quality of life, and currently, there is no radical cure. Abnormal mechanical stress is widely regarded as a core driver of OA pathogenesis, and the exploration of mechanical signal perception and transduction mechanisms has become crucial for deciphering OA’s pathophysiological processes. Piezo1, a key mechanosensitive cation channel belonging to the Piezo protein family, has recently gained significant attention due to its pivotal role in mediating cellular responses to mechanical stimuli in joint tissues. This review systematically examines Piezo1’s expression patterns, regulatory mechanisms, and pathological functions in OA, with a particular focus on its dual roles in modulating chondrocyte homeostasis and bone metabolism disorders, while also delving into the underlying molecular signaling pathways and potential therapeutic implications. Piezo1, consisting of approximately 2 500 amino acids and forming a unique trimeric propeller-like structure, is widely expressed in chondrocytes, osteocytes, mesenchymal stem cells, and synovial cells. It exhibits permeability to cations such as Ca2+, K+, and Na+, and directly responds to membrane tension changes induced by mechanical stimuli like fluid shear stress and mechanical overload. In OA patients and animal models, Piezo1 expression is significantly upregulated, especially in cartilage regions subjected to abnormal mechanical stress (e.g., human temporomandibular joint cartilage). This overexpression is closely associated with aggravated cartilage degeneration, increased chondrocyte apoptosis, accelerated cellular senescence, and intensified inflammatory responses. Mechanical overload and pro-inflammatory cytokines (e.g., IL-1β) are key inducers of Piezo1 upregulation: IL-1β activates the PI3K/AKT/mTOR signaling pathway to enhance Piezo1 expression, forming a pathogenic positive feedback loop that inhibits chondrocyte autophagy, promotes apoptosis, and further accelerates joint degeneration. Mechanistically, Piezo1 mediates OA progression through multiple interconnected pathways. When activated by mechanical stress, Piezo1 triggers excessive Ca2+ influx, leading to endoplasmic reticulum stress (ERS) and mitochondrial dysfunction, which directly induce chondrocyte apoptosis. This process involves the activation of downstream signaling cascades such as cGAS-STING and YAP-MMP13/ADAMTS5. YAP, a transcriptional regulator, upregulates the expression of matrix metalloproteinase 13 (MMP13) and aggrecanase (ADAMTS5), thereby accelerating cartilage matrix degradation. Additionally, Piezo1-driven Ca2+ overload promotes the accumulation of reactive oxygen species (ROS) and upregulates senescence markers (p16 and p21), accelerating chondrocyte senescence via the p38MAPK and NF-κB pathways. Senescent chondrocytes secrete senescence-associated secretory phenotype (SASP) factors (e.g., IL-6, IL-1β), further amplifying joint inflammation. In terms of bone metabolism, Piezo1 maintains joint homeostasis by promoting the differentiation of fibrocartilage stem cells into chondrocytes and balancing bone formation and resorption through regulating the FoxC1/YAP axis and RANKL/OPG ratio. Therapeutically, targeting Piezo1 shows promising potential. Preclinical studies have demonstrated that Piezo1 inhibitors (e.g., GsMTx4) can reduce joint damage and alleviate pain in OA mice. Simultaneously, siRNA-mediated co-silencing of Piezo1 and TRPV4 (another mechanosensitive channel) decreases intracellular Ca2+ concentration, inhibits chondrocyte apoptosis, and promotes cartilage repair. Conditional knockout of Piezo1 using Gdf5-Cre transgenic mice alleviates cartilage degeneration in post-traumatic OA models by downregulating MMP13 and ADAMTS5 expression. Despite existing challenges, such as off-target effects of inhibitors, inefficient local drug delivery, and interindividual genetic variability, strategies like developing selective Piezo1 antagonists, optimizing targeted nanocarriers, and combining Piezo1-targeted therapy with physical therapy provide viable avenues for clinical translation. The authors propose that Piezo1 serves as a critical therapeutic target for OA, and future research should focus on deciphering its context-dependent regulatory networks, developing tissue-specific intervention strategies, and validating their efficacy and safety in clinical trials to address the unmet medical needs of OA patients.
3.Resveratrol attenuates hepatic inflammation and oxidative stress in rheumatoid arthritis via Nrf2/Keap1 pathway
Xue-fei FAN ; Jian ZHOU ; Su-huan CHEN ; Meng-yan ZHANG ; Hao-miao LIU ; Rui SU ; Guang-yi CHEN ; Yu-bao SHAO ; Tao YAO ; Xiao-yu CHEN
Chinese Pharmacological Bulletin 2025;41(5):861-867
Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.
4.Moxibustion combined with low-dose tadalafil for diabetes mellitus-induced erectile dysfunction:A prospective,single-center,three-arm randomized controlled trial
Tao LIU ; Zhao-xu YANG ; Yan XU ; Qi ZHAO ; Xue LIU ; Xin-fei HUANG ; Zhi-xing SUN ; Yun CHEN ; Jian-huai CHEN
National Journal of Andrology 2025;31(1):55-60
Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0%)than in the Mox(46.7%)and TAD groups(60.0%)(P<0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P<0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P<0.05)in all the three groups(P<0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P<0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.
5.Outcomes of transcatheter transseptal mitral valve-in-valve replacement using Edward's SAPIEN 3 in high surgical risk patients-a multicenter study in China
Xiang CHEN ; Bin WANG ; Yi-wei XU ; Xiao-ping PENG ; Fan QIAO ; Xiang-wen LIANG ; Ke HAN ; Xiao-fei JIANG ; Xiang MA ; Wen-yi YANG ; Guo-sheng FU ; Mao-long SU ; Yan WANG
Chinese Journal of Interventional Cardiology 2025;33(2):79-86
Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0%being females and 70.0%classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0%technical success rate and a 90.0%procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0%)were re-hospitalized due to heart failure,and sadly,one of them(5.0%)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.
6.Bioequivalence study of desloratadine tablets in healthy Chinese subjects
Peng-fei XIE ; Yuan-lu CHEN ; Hong-di CUI ; Hui LONG ; Yong-gang ZHAO ; Qi-shan HUANG ; Peng YANG ; Yan ZHOU ; Yong-dong ZHANG
The Chinese Journal of Clinical Pharmacology 2025;41(2):220-224
Objective To explore the pharmacokinetic(PK)characteristics of desloratadine tablets and reference drugs in healthy subjects,and evaluate their bioequivalence and safety.Methods The random,open,two-period,cross-over pharmacokinetic study method was adopted,each subject received a single oral dose of desloratadine tablets test drug(T)or reference drug(R)for 5 mg.The concentrations of desloratadine and 3-hydroxy desloratadine in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS);and the PK parameters were calculated by WinNonlin 8.1 software to evaluate the bioequivalence.Results The main PK parameters of T and R of desloratadine were as follows:the fasting condition Cmax were respectively(3 809.82±1 016.54)and(3 642.36±777.07)pg·mL-1;AUC0-120h were respectively(5.75 ×104±5.03 ×104)and(5.51 × 104±4.00 × 104)pg·h·mL-1;AUC0-∞ were respectively(6.85× 104±1.03× 104)and(6.37 × 104±7.92 × 104)pg·h·mL-1.The fed condition Cmax were respectively(4 398.98±1 191.22)and(4 744.4±1 511.97)pg·mL-1;AUC0-120h were respectively(5.25 × 104±1.82 × 104)and(5.55 × 104±1.98 × 104)pg·h·mL-1;AUC0-∞ were respectively(5.37 × 104±1.86 × 104)and(5.68 × 104±2.04 × 104)pg·h·mL-1.The 90%confidence interval of Cmax,AUC0-t and AUC0-∞ of desloratadine were all within 80.00%~125.00%.Conclusion There was no significant difference in the main PK parameters between T tablets and R under fasting or high-fat postprandial conditions,and desloratadine tablets were bioequivalent,safe and well tolerated.
7.Study on intestinal protection and mechanism of magnolol in neonatal rats with necrotizing enterocolitis
Hai-yan FENG ; Yue ZHANG ; Mao XU ; Kai-qi TAN ; Yi WANG ; Zhuo-lin CHEN ; Yu-fei CHEN ; Shao-xuan CHEN ; Yang ZHAO ; Cui LIU
Chinese Pharmacological Bulletin 2025;41(9):1728-1735
Aim To investigate the intestinal protection and possible mechanism of magnolol(MG)in newborn rats with necrotizing enterocolitis(NEC).Methods The rats were randomly divided into control group(Ctrl group),model group(NEC group)and treatment group(MG group).The NEC model was induced by hypoxia,cold stimulation,deep formula milk and LPS intragastric administration in 7-day-old rats for four days.They were killed after five days of treatment with MG(20 mg·kg-1).HE staining was used to observe the intestinal pathological injury.Western blot was used to detect the expressions of IL-1 β,TNF-α,NL-RP3,ASC,caspase-1 and tight junction protein in the distal ileum of rats.Colon contents were collected for 16S rDNA sequencing to understand the gut microbio-ta.Results MG improved the body mass and intesti-nal injury of NEC neonatal rats.The expressions of in-testinal IL-1β,TNF-α,NLRP3,ASC and caspase-1 proteins were down-regulated,and the expressions of Claudin,Occludin and ZO-1 proteins were up-regula-ted.16S rDNA showed that MG increased the diversity of intestinal flora,and at the phylum level,MG in-creased the abundance of firmicutes and bacteroides in NEC model,and decreased the abundance of pro-teobacteria.At the genus level,MG treatment in-creased the abundance of Lactobacillus,unclassified_Muribaculaceae,Racteroides,but decreased the abun-dance of Escherichia_Shigella,Rodentibacter and Fuso-bacterium.Conclusion MG intervention can protect the intestinal tract of NEC rats by potentially improving barrier function,and regulating the intestinal microbiota through the NLRP3/ASC/caspase-1 signaling pathway.
8.Devevelopment and application of carriage-type field operating unit
Yong-xiang FAN ; Peng-fei JI ; Xiao-lei WANG ; Li LIN ; Yan CHEN ; Ming-cui SUN
Chinese Medical Equipment Journal 2025;46(8):113-117
Objective To develop a carriage-type field operating unit with advantages in mobility and rapid deployment to solve the problems of the traditional field operating equipment in flexibility and environmental adaptability.Methods The carriage-type field operating unit was made based on a BEIBEN TRUCK transport vehicle platform with external and internal modifications.The external modification involved a hydraulic loading platform with a capacity of 2 t and electric lifting function at the rear of the carriage and an external equipment compartment at the bottom.The internal modification included area renovation,tarp modification,facility remodeling and equipment configuration.Results The carriage-type field operating unit behaved better than the traditional field operating vehicle and operating shelter in deployment time,infection control,mobility,temperature control,etc.Conclusion The carriage-type field operating unit gains advantages in mobility,rapid deployment and complete supporting facilities,and can be used as a relatively independent field surgical unit.[Chinese Medical Equipment Journal,2025,46(8):113-117]
9.Resveratrol attenuates hepatic inflammation and oxidative stress in rheumatoid arthritis via Nrf2/Keap1 pathway
Xue-fei FAN ; Jian ZHOU ; Su-huan CHEN ; Meng-yan ZHANG ; Hao-miao LIU ; Rui SU ; Guang-yi CHEN ; Yu-bao SHAO ; Tao YAO ; Xiao-yu CHEN
Chinese Pharmacological Bulletin 2025;41(5):861-867
Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxida-tive stress in rheumatoid arthritis(RA),and to eluci-date the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken type Ⅱ collagen in combination with complete Freund's adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflam-mation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L-1),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-relat-ed indices were detected by protein blotting.The in-trinsic mechanisms by which Res attenuated hepatic in-flammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res signifi-cantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates he-patic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.
10.Influence of Shumian Capsules Combined with Quetiapine on Negative Symptoms,Sleep Quality and Neurotransmitters in Patients with Schizophrenia
Fei-yan CHEN ; Jian-yi XU ; Hong LIN
Progress in Modern Biomedicine 2025;25(18):2973-2980
Objective:This prospective study is conducted to explored the influence of Shumian Capsules combine with quetiapine on negative symptoms,sleep quality and neurotransmitters in patients with schizophrenia.Methods:50 patients with schizophrenia admitted to Fuzhou Gulou District Hospital of Fujian Province from April 2022 to May 2024 were retrospectively selected as the study group.According to the principle of 1∶1 matching cases,50 patients with schizophrenia in the same period were selected as the reference group.Reference group received quetiapine treatment,while study group was treated with Shumian capsules on the basis of the reference group.Negative symptom scale(SANS),positive and negative symptom scale(PANSS),Pittsburgh sleep quality index(PSQI),social-skills for psychiatric inpatients(SSPI),treatment emergent symptom scale(TESS),self-rating anxiety scale SAS),self-rating depression scale(SDS)score,neurotransmitter levels[γ-aminobutyric acid(GABA),brain-derived neurotrophic factor(BDNF),glutamic acid(Glu)and the occurrence of adverse reactions were compared between the two groups.Results:The scores of SANS,PANSS,PSQI,TESS,SAS,SDS and Glu levels decreased 4 weeks and 8 weeks after treatment in both groups,and study group were lower than those in reference group,SSPI score and GABA and BDNF levels increased,and study group were higher than those in the reference group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Shumian Capsules combined with quetiapine can effectively improve negative symptoms,sleep quality and neurotransmitters in patients with schizophrenia,and have good safety.

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