Objective To construct a model of knee osteoarthritis(KOA)through the co-culture of dorsal root ganglia(DRG)and fibroblast-like synoviocytes(FLSs).To investigate the effects of transient receptor potential vanilloid type 1(TRPV1)desensitization of sensory neurons induced by mechanical stimulation,including the alleviation of the FLSs inflammatory response.Methods DRG neuronal cells were identified through immunofluorescence.The stress loading of DRG neurons was realized using the FX-6000T cell stress system,and the effect of mechanical strain on the activity of DRG neurons was measured using the CCK-8 method.Ca2+ion flux in DRG neurons was studied through flow cytometry.A Transwell chamber and FLSs were used to establish a co-culture system.The contents of the pro-inflammatory factors IL-1β,TNF-α,and TGF-β in the supernatant were determined by ELISA.Gene and protein expression levels of TRPV1 and its desensitizing negative regulatory proteins PP2B,CaM,IL-1β,TNF-α,TGF-β,and α-SMA in DRG neurons were evaluated using RT-qPCR and Western blot,respectively.Results The Ca2+ion flux in DRG neurons increased under inflammatory conditions,and low intensity(sinusoidal,2％,1 Hz,6 h)thumb-pressing-induced mechanical stimulation did not alter Ca2+ion flux(P＞0.05).However,middle intensity(sinusoidal,4％,1 Hz,6 h)and high intensity(sinusoidal,8％,1 Hz,6 h)stimulation increased Ca2+ion flux significantly(P＜0.05).Notably,high intensity stimulation did not lead to a further increase in Ca2+ion flux over that for middle intensity stimulation(P＞0.05).There was no significant effect of low intensity stimulation on TRPV1,PP2B,or CaM gene or protein expression in DRG neurones,on IL-1β,TNF-α,or TGF-βconcentrations in the supernatant of co-cultured cells,or on IL-1β,TNF-α,TGF-β,or α-SMA gene or protein expression in FLSs(P＞0.05).Middle and high intensity mechanical stimulation up-regulated TRPV1 at the gene and protein expression levels in DRG neurons in the inflammatory group(P＜0.05)but down-regulated PP2B and CaM at the gene and protein expression levels(P＜0.05).Middle and high intensity mechanical stimulation decreased IL-1β,TNF-α,and TGF-β levels in the supernatants of co-cultured cells(P＜0.05)and decreased the gene and protein expression levels of IL-1β,TNF-α,TGF-β,and α-SMA in FLSs(P＜0.05).Conclusions Middle and high intensity thumb-pressing-induced mechanical stimulation induced TRPV1 desensitization of rat sensory neurons,reduced the release of pain mediators,and suppressed the FLSs inflammatory response through downregulating IL-1β,TNF-α,and TGF-β.

Objective:To compare the clinical efficacy of Chevron-Akin osteotomy with cannulated compression screw and absorbable screw fixation in the treatment of moderate and severe hallux valgus.Methods:The data of 52 patients with moderate to severe hallux valgus treated in Sichuan Provincial Orthopaedic Hospital from January 2020 to December 2022 were retrospectively analyzed. According to the fixation method, they were divided into metal screw group and absorbable screw group. In the metal screw group, there were 25 cases (26 feet), 2 males (2 feet) and 23 females (24 feet), aged 36.7±4.9 years (range, 21-59 years), 12 feet on the left side, 14 feet on the right side, moderate 20 feet and severe 6 feet. There were 27 cases (29 feet) in the absorbable screw group, including 1 male (1 foot) and 26 female (28 feet), aged 34.1±5.5 years (range, 19-56 years), 16 feet on the left side, 13 feet on the right side, moderate 22 feet and severe 7 feet. The healing time and complications of osteotomy were recorded between the two groups, and the hallux valgus angle (HVA), first-second intermetatarsal angle (1-2 IMA), American Orthopaedic Foot and Ankle Society (AOFAS), hallux-metatarsophalangeal-interphalangeal joint score and visual analogue scale (VAS) for pain were compared before and after the operation.Results:All 52 patients were followed up. The follow-up time was 14.0±3.4 months (range, 11-27 months) in the metal screw group and 15.1±2.7 months (range, 13-24 months) in the absorbable screw group. In all patients, the incision healed in one stage, and no endovegetal rejection occurred. The osteotomy healing time was 3.8±0.8 months (range, 2-5 months) in the metal screw group and 3.4±1.1 months (range, 2.5-5 months) in the absorbable screw group, with no statistically significant difference ( t=1.014, P=0.417). In the metal screw group, there were symptoms of medial internal fixation irritation in 2 feet, medial osteophyte or thread knot irritation in 2 feet, and hallux valgus recurrence in 1 foot. The complication rate was 19%(5/26). In the absorbable screw group, medial osteophyte or thread knot stimulated one foot and hallux valgus recurred one foot, and the complication rate was 7%(2/29). The difference in complications between the two groups was statistically significant (χ 2=8.051, P=0.012). At 12 months after operation, for the metal screw group and the absorbable screw group, HVA (13.7°±2.1° and 12.9°±3.8°), 1-2 IMA (7.2°±1.5° and 7.8°±1.2°), AOFAS score (91.4±2.2 and 90.8±3.6 points) and VAS score (1.1±0.3 and 1.3±0.4 points), respectively, were significantly higher than those in the preoperative (HVA: 37.2°± 5.4° and 35.8°±4.7°, 1-2 IMA: 18.3°± 1.8° and 17.9°±1.7°, AOFAS score: 60.4±5.6 and 58.4±7.1 points, VAS: 6.4±0.6 and 6.8±0.4 points) improvement ( P<0.05), while there was no statistically significant difference between the two groups ( P>0.05). The incidence of complications in metal screw group was 19%(5/26), while in absorbable screw group it was 7%(2/29), with a statistically significant difference (χ 2=8.051, P=0.012). Conclusions:Both cannulated compression screw in Chevron-Akin osteotomy and absorbable screw fixation can have a good fixation effect in the treatment of moderate and severe hallux valgus. Absorbable screw fixation has the advantages of low complication rate, less interference with artifacts in later imaging examination and evaluation.

Objective To construct a model of knee osteoarthritis(KOA)through the co-culture of dorsal root ganglia(DRG)and fibroblast-like synoviocytes(FLSs).To investigate the effects of transient receptor potential vanilloid type 1(TRPV1)desensitization of sensory neurons induced by mechanical stimulation,including the alleviation of the FLSs inflammatory response.Methods DRG neuronal cells were identified through immunofluorescence.The stress loading of DRG neurons was realized using the FX-6000T cell stress system,and the effect of mechanical strain on the activity of DRG neurons was measured using the CCK-8 method.Ca2+ion flux in DRG neurons was studied through flow cytometry.A Transwell chamber and FLSs were used to establish a co-culture system.The contents of the pro-inflammatory factors IL-1β,TNF-α,and TGF-β in the supernatant were determined by ELISA.Gene and protein expression levels of TRPV1 and its desensitizing negative regulatory proteins PP2B,CaM,IL-1β,TNF-α,TGF-β,and α-SMA in DRG neurons were evaluated using RT-qPCR and Western blot,respectively.Results The Ca2+ion flux in DRG neurons increased under inflammatory conditions,and low intensity(sinusoidal,2％,1 Hz,6 h)thumb-pressing-induced mechanical stimulation did not alter Ca2+ion flux(P＞0.05).However,middle intensity(sinusoidal,4％,1 Hz,6 h)and high intensity(sinusoidal,8％,1 Hz,6 h)stimulation increased Ca2+ion flux significantly(P＜0.05).Notably,high intensity stimulation did not lead to a further increase in Ca2+ion flux over that for middle intensity stimulation(P＞0.05).There was no significant effect of low intensity stimulation on TRPV1,PP2B,or CaM gene or protein expression in DRG neurones,on IL-1β,TNF-α,or TGF-βconcentrations in the supernatant of co-cultured cells,or on IL-1β,TNF-α,TGF-β,or α-SMA gene or protein expression in FLSs(P＞0.05).Middle and high intensity mechanical stimulation up-regulated TRPV1 at the gene and protein expression levels in DRG neurons in the inflammatory group(P＜0.05)but down-regulated PP2B and CaM at the gene and protein expression levels(P＜0.05).Middle and high intensity mechanical stimulation decreased IL-1β,TNF-α,and TGF-β levels in the supernatants of co-cultured cells(P＜0.05)and decreased the gene and protein expression levels of IL-1β,TNF-α,TGF-β,and α-SMA in FLSs(P＜0.05).Conclusions Middle and high intensity thumb-pressing-induced mechanical stimulation induced TRPV1 desensitization of rat sensory neurons,reduced the release of pain mediators,and suppressed the FLSs inflammatory response through downregulating IL-1β,TNF-α,and TGF-β.

Objective:To compare the clinical efficacy of Chevron-Akin osteotomy with cannulated compression screw and absorbable screw fixation in the treatment of moderate and severe hallux valgus.Methods:The data of 52 patients with moderate to severe hallux valgus treated in Sichuan Provincial Orthopaedic Hospital from January 2020 to December 2022 were retrospectively analyzed. According to the fixation method, they were divided into metal screw group and absorbable screw group. In the metal screw group, there were 25 cases (26 feet), 2 males (2 feet) and 23 females (24 feet), aged 36.7±4.9 years (range, 21-59 years), 12 feet on the left side, 14 feet on the right side, moderate 20 feet and severe 6 feet. There were 27 cases (29 feet) in the absorbable screw group, including 1 male (1 foot) and 26 female (28 feet), aged 34.1±5.5 years (range, 19-56 years), 16 feet on the left side, 13 feet on the right side, moderate 22 feet and severe 7 feet. The healing time and complications of osteotomy were recorded between the two groups, and the hallux valgus angle (HVA), first-second intermetatarsal angle (1-2 IMA), American Orthopaedic Foot and Ankle Society (AOFAS), hallux-metatarsophalangeal-interphalangeal joint score and visual analogue scale (VAS) for pain were compared before and after the operation.Results:All 52 patients were followed up. The follow-up time was 14.0±3.4 months (range, 11-27 months) in the metal screw group and 15.1±2.7 months (range, 13-24 months) in the absorbable screw group. In all patients, the incision healed in one stage, and no endovegetal rejection occurred. The osteotomy healing time was 3.8±0.8 months (range, 2-5 months) in the metal screw group and 3.4±1.1 months (range, 2.5-5 months) in the absorbable screw group, with no statistically significant difference ( t=1.014, P=0.417). In the metal screw group, there were symptoms of medial internal fixation irritation in 2 feet, medial osteophyte or thread knot irritation in 2 feet, and hallux valgus recurrence in 1 foot. The complication rate was 19%(5/26). In the absorbable screw group, medial osteophyte or thread knot stimulated one foot and hallux valgus recurred one foot, and the complication rate was 7%(2/29). The difference in complications between the two groups was statistically significant (χ 2=8.051, P=0.012). At 12 months after operation, for the metal screw group and the absorbable screw group, HVA (13.7°±2.1° and 12.9°±3.8°), 1-2 IMA (7.2°±1.5° and 7.8°±1.2°), AOFAS score (91.4±2.2 and 90.8±3.6 points) and VAS score (1.1±0.3 and 1.3±0.4 points), respectively, were significantly higher than those in the preoperative (HVA: 37.2°± 5.4° and 35.8°±4.7°, 1-2 IMA: 18.3°± 1.8° and 17.9°±1.7°, AOFAS score: 60.4±5.6 and 58.4±7.1 points, VAS: 6.4±0.6 and 6.8±0.4 points) improvement ( P<0.05), while there was no statistically significant difference between the two groups ( P>0.05). The incidence of complications in metal screw group was 19%(5/26), while in absorbable screw group it was 7%(2/29), with a statistically significant difference (χ 2=8.051, P=0.012). Conclusions:Both cannulated compression screw in Chevron-Akin osteotomy and absorbable screw fixation can have a good fixation effect in the treatment of moderate and severe hallux valgus. Absorbable screw fixation has the advantages of low complication rate, less interference with artifacts in later imaging examination and evaluation.

Under the background of carbon peaking and carbon neutrality goals, the Ministry of Ecology and Environment, together with 15 national ministries and commissions, has formulated the Implementation Plan on Establishing a Carbon Footprint Management System, and it is urgent for traditional Chinese medicine(TCM) pharmaceutical enterprises to carry out research on carbon footprint accounting methods of related products. Based on the life cycle assessment(LCA) theory, taking mulberry leaf extract produced by a certain enterprise as an example, this study analyzed the carbon footprint of TCM extracts during the life cycle. The results show that for every 1 kg of product produced, the carbon emissions from the stages of raw material acquisition, transportation, and extract production are-20.569, 1.205, and 173.577 kgCO_2eq(CO_2 equivalent), respectively. The carbon footprint of the product is 154.213 kgCO_2eq·kg~(-1). In addition, the carbon emission is the highest in the production stage, in which the consumption of ethanol solvents makes the greatest contribution to the carbon footprint, accounting for 25.71%, more than one-fourth of the total carbon footprint. The second contribution was from the treatment process of TCM residues, accounting for 19.67%, closely followed by wastewater treatment(17.71%), the consumption of hot steam(17.43%), and drinking water(16.90%). The consumption of electric power and packaging materials has a smaller carbon emission of 2.58%. In particular, the carbon emission caused by the consumption of packaging materials is only 0.04%, which is negligible. The results of the study are expected to provide a reference for TCM enterprises to carry out research on the carbon footprint of products, offer ideas for collaborative innovation in reducing pollution and carbon emissions throughout the entire industry chain of TCM, and develop new quality productivity of modern TCM industry based on green and low-carbon manufacturing.
Morus/chemistry* ; Plant Leaves/chemistry* ; Carbon Footprint ; Drugs, Chinese Herbal/chemistry* ; Plant Extracts/analysis* ; Medicine, Chinese Traditional

At present, the cause of traditional Chinese medicine(TCM) in China has entered a new period of high-quality development. How to strengthen the foundation for the TCM industry from the source is an important issue that deserves the attention of the authorities, industry, and academia. This study systematically analyzed the regulatory system of TCM raw materials and preparations. The study took the TCM industry chain and the product life cycle as a clue and focused on the dimensions of TCM resource protection and plant cultivation(farming), production and quality supervision of TCM raw materials and preparations, and their market access and distribution. It analyzed the current situation of the regulation of TCM raw materials and preparations under the regulatory system of drugs, discussed the main problems, and put forward corresponding suggestions. The results can provide an important reference value for the subsequent improvement of the regulatory system of drugs and the construction of a prominent regulatory system of drugs in accordance with TCM characteristics.
Drugs, Chinese Herbal/economics* ; Medicine, Chinese Traditional/standards* ; China ; Quality Control ; Humans ; Plants, Medicinal/chemistry*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To investigate the role of poly(rC)-binding protein 1(PCBP1)in cadmium(Cd)-induced ferroptosis in mouse neuroblastoma Neuro-2a(N2A)cells.Methods N2A cells were exposed to a concentration gradient of CdCl?(0,1,2,4 μmol/L)for 72 h.Cell viability was assessed by trypan blue staining.Western blotting was employed to detect the expression of ferroptosis-related proteins(GPX4,HMOX1,ACSL4)and PCBP1.Intracellular Fe2? level and lipid peroxidation were detected using FerroOrange and BODIPY581/591 C11 probes,respectively.Ferrostatin-1(Fer-1),a ferroptosis inhibitor,was applied to confirm the critical role of ferroptosis in Cd-induced cytotoxicity.Molecular docking was performed to elucidate the interaction between PCBP1 and ferritin,as well as the binding sites of Cd2?.PCBP1 overexpression plasmid was further constructed for functional validation.Results Cd exposure suppressed cell viability in N2A cells in a dose-dependent manner(P<0.01),significantly down-regulated GPX4 expression(P<0.05),up-regulated HMOX1 expression(P<0.01),and induced Fe2? overload and lipid peroxidation(P<0.01).Molecular docking revealed that Cd2? directly bound to the KH2 domain of PCBP1 and then co-localized on the outer surface of ferritin heavy chain.Overexpression of PCBP1 markedly reversed Cd-induced Fe2? accumulation,GPX4 down-regulation,lipid peroxidation,and cell death.Conclusion Cd exposure disrupts PCBP1-mediated iron homeostasis via transcriptional suppression and competitive displacement of metal ions,and then synergistically drives Fe2? overload-triggered ferroptosis cascades,ultimately leading to neurotoxicity.Targeting PCBP1-mediated iron homeostasis can effectively mitigate Cd-induced neurotoxicity,and may serve as a novel therapeutic strategy.

As a complex autoimmune disease， rheumatoid arthritis （RA） involves immune microenvironment dysregulation resulting from excessive activation of pyroptosis， which is a crucial factor in disease progression. Based on the theory of ying-wei in traditional Chinese medicine， "ying decline and wei attack" is considered the fundamental pathogenesis of RA. Pyroptosis serves as a microscopic manifestation of this concept， suggesting a potential correlation between "ying decline and wei attack" and pyroptosis nd immune microenvironment dysregulation in RA. Accordingly， treatment principles based on this theory are proposed： in the early stage of the disease， boosting wei to consolidate the exterior， and regulating ying to dispel pathogens； in the middle and late stages， harmonizing ying to remove stagnation， and nourishing its transformational source.