Since the promulgation of the first Drug Administration Law of the People's Republic of China 40 years ago in 1984, China has undergone four main stages in the traditional Chinese medicine(TCM) regulation: the initial establishment of TCM regulation rules(1984-1997), the formation of a modern TCM regulatory system(1998-2014), the reform of the review and approval system for new TCM drugs(2015-2018), and the construction of a scientific regulation system for TCM(2019-2024). Over the past five years, a series of milestone achievements of TCM regulation in China have been achieved in the six aspects, including its strategic objectives and the establishment of a science-based regulatory system, the reform of the review and approval system for new TCM drugs, the optimization and improvement of the TCM standard system and its formation mechanism, comprehensive enhancement of regulatory capabilities for TCM safety, international harmonization of TCM regulation and its role in promoting innovation. Looking ahead, centered on advancing TCMRS to establish a sound regulatory framework tailored to the unique characteristics of TCM, TCM regulation will evolve into new reform patterns, advancing and extending across eight critical fronts, including the legal framework and policy architecture, the review and approval system for new TCM drugs, the quality standard and management system of TCM, the comprehensive quality & safety regulation and traceability system, the research and transformation system for TCMRS, AI-driven innovations in TCM regulation, the coordination between high-quality industrial development and high-level regulation, and the leadership in international cooperation and regulatory harmonization. In this way, a unique path for the development of modern TCM regulation with Chinese characteristics will be pioneered.
Humans ; China ; Drugs, Chinese Herbal/standards* ; History, 20th Century ; History, 21st Century ; Medicine, Chinese Traditional/trends*

OBJECTIVE: Hepatocellular carcinoma (HCC) is sensitive to ferroptosis, a new form of programmed cell death that occurs in most tumor types. However, the mechanism through which ferroptosis modulates HCC remains unclear. This study aimed to investigate the oncogenic role and prognostic value of FANCD2 and provide novel insights into the prognostic assessment and prediction of immunotherapy. METHODS: Using clinicopathological parameters and bioinformatic techniques, we comprehensively examined the expression of FANCD2 macroscopically and microcosmically. We conducted univariate and multivariate Cox regression analyses to identify the prognostic value of FANCD2 in HCC and elucidated the detailed molecular mechanisms underlying the involvement of FANCD2 in oncogenesis by promoting iron-related death. RESULTS: FANCD2 was significantly upregulated in digestive system cancers with abundant immune infiltration. As an independent risk factor for HCC, a high FANCD2 expression level was associated with poor clinical outcomes and response to immune checkpoint blockade. Gene set enrichment analysis revealed that FANCD2 was mainly involved in the cell cycle and CYP450 metabolism. CONCLUSION To the best of our knowledge, this is the first study to comprehensively elucidate the oncogenic role of FANCD2. FANCD2 has a tumor-promoting aspect in the digestive system and acts as an independent risk factor in HCC; hence, it has recognized value for predicting tumor aggressiveness and prognosis and may be a potential biomarker for poor responsiveness to immunotherapy.
Humans ; Carcinoma, Hepatocellular/diagnosis* ; Liver Neoplasms/diagnosis* ; Immunotherapy ; Fanconi Anemia Complementation Group D2 Protein/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/metabolism*

PURPOSE: To compare the efficacy of continuous renal replacement therapy (CRRT) using either oXiris or conventional hemopurification filters in the treatment of intra-abdominal sepsis. METHODS: We conducted a retrospective analysis of septic patients with severe intra-abdominal infections admitted to our hospital from October 2019 to August 2023. Patients who meet the criteria for intra-abdominal sepsis based on medical history, symptoms, physical examination, and laboratory/imaging findings were included. EXCLUSION CRITERIA: pregnancy, terminal malignancy, prior CRRT before intensive care unit admission, pre-existing liver or renal failure. Heart rate (HR), mean arterial pressure, oxygenation index, lactic acid level (Lac), platelet count (PLT), neutrophil percentage, serum levels of procalcitonin, C-reactive protein, interleukin (IL)-6, norepinephrine dosage, acute physiology and chronic health evaluation II (APACHE II), and sequential organ failure assessment (SOFA) scores before and after 24 h and 72 h of treatment, as well as ventilator use time, hemopurification treatment time, intensive care unit and hospital lengths of stay, and 14-day and 28-day mortality were compared between patients receiving CRRT using either oXiris or conventional hemofiltration. Statistical analysis was performed using SPSS Statistics 26.0 software, including the construction of predictive models via logistic regression equations and repeated measures ANOVA. RESULTS: Baseline values including time to antibiotic administration, time to source control, and time to initiation of CRRT were similar between the 2 groups (all p>0.05). Patients receiving conventional CRRT exhibited significant changes in HR but of none of the other indexes at the 24 h and 72 h time points (p=0.041, p=0.026, respectively). The oXiris group showed significant improvements in HR, Lac, IL-6, and APACHE II score 24 h after treatment (p<0.05); after 72 h, all indexes were improved except PLT (all p<0.05). Intergroup comparison disclosed significant differences in HR, Lac, norepinephrine dose, APACHE II, SOFA, neutrophil percentage, and IL-6 after 24 h of treatment (p<0.05). Mean arterial pressure, serum levels of procalcitonin, C-reactive protein, SOFA score, and norepinephrine dosage were similar between the 2 groups at 24 h (p>0.05). Except for HR, oxygenation index, and PLT, post-treatment change rates of △ (%) were significantly greater in the oXiris group (p < 0.05). Duration of ventilator use, CRRT time, and intensive care unit and hospital lengths of stay were similar between the 2 groups (p>0.05). The 14-day mortality rates of the 2 groups were similar (p=0.091). After excluding patients whose CRRT was interrupted, 28-day mortality was significantly lower in the oXiris than in the conventional group (25.0% vs. 54.2%; p=0.050). The 28-day mortality rate increased by 9.6% for each additional hour required for source control and by 21.3% for each 1-point increase in APACHE II score. CONCLUSIONS In severe abdominal infections, the oXiris filter may have advantages over conventional CRRT, which may provide an alternative to clinical treatment. Meanwhile, early active infection source control may reduce the case mortality rate of patients with severe abdominal infections.
Humans ; Retrospective Studies ; Female ; Male ; Middle Aged ; Sepsis/mortality* ; Aged ; Adult ; Continuous Renal Replacement Therapy/methods* ; Intraabdominal Infections/mortality* ; APACHE ; Organ Dysfunction Scores ; Intensive Care Units ; Treatment Outcome

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 evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

Objective:To investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.Methods:The experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups. Results:① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05). Conclusions:Overactivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Calcified lesions increase the difficulty of interventional therapy for coronary heart disease,and increase the risk of perioperative and long-term complications.Pretreatment of calcified lesions is very important.Coronary lithotripsy(IVL)is used more and more in calcified lesions,and many clinical trials have proved its effectiveness and safety.Stent underexpansion is an important risk factor for stent thrombosis and restenosis,which increases the incidence of complications.At present,there is no effective coping strategy or clear consensus or guidelines for the treatment of stent underexpansion caused by calcified lesions.There are few reports about the treatment of stent under expansion by IVL,and most of them are case reports and small sample studies.In this paper,two cases of stent under expansion were reported.After stent implantation,stent under expansion was found,and IVL was used to treat the cases,which achieved good results.This paper reports 2 cases of stent under expansion to explore the efficacy and safety of IVL in the treatment of such lesions.