BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

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

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver condition globally, lacks adequate and effective therapeutic remedies in clinical practice. Recent studies have increasingly highlighted the close connection between the ubiquitin-proteasome system (UPS) and the progression of MASLD. This relationship is crucial for understanding the disease's underlying mechanism. As a sophisticated process, the UPS govern protein stability and function, maintaining protein homeostasis, thus influencing a multitude of elements and biological events of eukaryotic cells. It comprises four enzyme families, namely, ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), ubiquitin-protein ligases (E3), and deubiquitinating enzymes (DUBs). This review aims to delve into the array of pathways and therapeutic targets implicated in the ubiquitination within the pathogenesis of MASLD. Therefore, this review unveils the role of ubiquitination in MASLD while spotlighting potential therapeutic targets within the context of this disease.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To explore the therapeutic mechanism of hot compress with Sangzhi Shengjiang Decoction(manily composed of Zingiberis Rhizoma Recens,Mori Ramulus,Cinnamomi Ramulus,Speranskiae Tuberculatae Herba,and Cervi Cornus Colla)in relieving pain and improving hemorheology of patients with femoral head necrosis(FHN).Methods A total of 104 patients with FHN who admitted to Guang'anmen Hospital Baoding,China Academy of Chinese Medical Sciences from May 2022 to May 2024 were randomly divided into the control group and the treatment group according to the random number table method,with 52 cases in each group.The control group was treated with Alendronate Sodium orally,and the treatment group was given hot compress with Sangzhi Shengjiang Decoction on the basis of treatment for the control group.The course of treatment for the two groups covered three months.Before and after the treatment,the traditional Chinese medicine(TCM)syndrome score,Harris score of joint function,Visual Analogue Scale(VAS)score for pain,and the levels of hemorheology indicators,bone metabolism indicators,and bone mineral density(BMD)of proximal femur and lumbar trabecular bone in the two groups were observed.After treatment,the clinical efficacy of patients in the two groups was evaluated.Results(1)After three months of treatment,the total effective rate of the treatment group was 92.31％(48/52)and that of the control group was 71.15％(37/52),and the intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the treatment group was significantly superior to that of the control group(P<0.01).(2)After treatment,the scores of TCM symptoms such as soreness and weakness in the waist and knee,claudication,restlessness and insomnia,and soreness and heaviness of lower limbs in the two groups were decreased compared with those before treatment(P<0.05),and the decreases in the treatment group were significantly superior to that in the control group(P<0.01).(3)After treatment,the Harris scores of joint function in the two groups were increased(P<0.05)and the VAS scores for pain were decreased compared with those before treatment(P<0.05),and the increase of Harris scores and the decrease of VAS scores in the treatment group were significantly superior to those in the control group(P<0.01).(4)After treatment,the levels of hemorheology indicators such as erythrocyte sedimentation rate(ESR),whole blood low-shear viscosity(LBV),and whole blood high-shear viscosity(HBV)in the two groups were improved compared with those before treatment(P<0.05),and the improvement in the treatment group was significantly superior to that in the control group(P<0.01).(5)After treatment,the levels of bone metabolism indicators such as serum N-terminal mid-fragment of osteocalcin(N-MID)β-C-terminal telopeptide of type Ⅰ collagen(β-CTX)and total procollagen type Ⅰ N-terminal propeptide(T-PINP)levels of patients in the two groups were decreased compared with those before treatment(P<0.05),and serum 25-hydroxy vitamin D[25-(OH)D]level was increased compared with that before treatment(P<0.05).The decrease of serum N-MID,β-CTX and T-PINP levels and the increase of serum 25-(OH)D level in the treatment group were significantly superior to those in the control group(P<0.01).(6)After treatment,BMD of proximal femur and lumbar trabecular bone in the two groups was increased compared with that before treatment(P<0.05),and the increase in the treatment group was significantly superior to that in the control group(P<0.01).Conclusion Hot compress with Sangzhi Shengjiang Decoction exerts certain efficacy for the treatment of patients with FHN.The therapy is effective on reducing the scores of TCM syndrome,relieving pain,improving joint function,regulating bone metabolism and bone density,improving hemorheology indicators,and presenting remarkable therapeutic effect.

Objective To observe the therapeutic effect and mechanism of electroacupuncture at Yanglingquan(GB34)and Quchi(LI11)points for post-stroke spasticity(PSS)in rats.Methods The rats were randomly divided into sham-operated group,model group,electroacupuncture group and electroacupuncture+CA1[Janus kinase 2(JAK2)agonist]group.The PSS model was prepared by the modified middle cerebral artery occlusion combined with internal capsule injection of N-methyl-D-aspartate(NMDA)receptor method in all groups of rats except the sham-operated group.After the intervention,the neurological deficit scale scoring,Ashworth Spasticity Scale(Ashworth)scoring and electrophysiological determination were carried out;the levels of interleukin 6(IL-6),tumor necrosis factor α(TNF-α)and γ-aminobutyric acid(GABA)in the brain tissues were detected by enzyme-linked immunosorbent assay(ELISA);the content of glutamate(Glu)was observed by colorimetry;the pathological changes in brain tissues were observed by hematoxylin-eosin(HE)staining method;the protein expression levels of JAK2,phosphorylated JAK2(p-JAK2),signal transducer and activator of transcription 3(STAT3),and phosphorylated STAT3(p-STAT3)in brain tissues were detected by Western Blot method.Results The neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues in the model group were all significantly higher than those in the sham-operated group(P<0.05),and the muscular tension signal value and GABA content in brain tissues in the model group were significantly lower than those in the sham-operated group(P<0.05);compared with the model group,the neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues were significantly lower in the electroacupuncture group(P<0.05),and the muscular tension signal value and GABA content in brain tissues were significantly higher in the electroacupuncture group(P<0.05);compared with the electroacupuncture group,the neurological deficit scale scores,Ashworth scores,contents of IL-6,TNF-α and Glu as well as p-JAK2/JAK2 and p-STAT3/STAT3 ratios in brain tissues in the electroacupuncture+CA1 group were significantly higher(P<0.05),and the muscular tension signal value and GABA content in brain tissues in the electroacupuncture+CA1 group were significantly lower(P<0.05).Conclusion Electroacupuncture may inhibit inflammatory responses and regulate the neuronal excitation/inhibition balance by inhibiting the JAK2/STAT3 pathway,thus relieving PSS in rats.

Objective To explore the mechanism of Taohong Siwu Decoction in recovering joint muscle strength and bone mineral density(BMD)in patients after hip preservation surgery for osteonecrosis of the femoral head(ONFH).Methods A total of 110 ONFH patients admitted to Guang'anmen Hospital Baoding Branch,China Academy of Chinese Medical Sciences from April 2022 to April 2024 were enrolled.The patients were equally randomized into a control group and a study group using a random number table,with 55 cases in each group.All patients underwent core decompression surgery and then were given postoperative conventional western medical treatment,and the study group received additional modified Taohong Siwu Decoction.The course of treatment lasted for 8 weeks.Before and after treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,Visual Analogue Scale(VAS)score for pain,Harris hip score,joint muscle strength,bone mineral density(BMD),hemorheological parameters(including plasma viscosity,whole blood high-shear viscosity,and whole blood low-shear viscosity),and bone metabolism markers[including alkaline phosphatase(ALP),osteocalcin(BGP),and bone morphogenetic protein 2(BMP-2)].After treatment,the clinical efficacy was evaluated between groups.Results(1)After 8 weeks of treatment,the total effective rate in the study group was 92.73%(51/55),which was significantly higher than that in the control group(72.73%,40/55).The intergroup comparison showed a statistically significant difference(χ2=7.698,P＜0.01).(2)After treatment,scores for hip pain,soreness and weakness of the lower back and knees,mental fatigue,and deep-thin-choppy pulse decreased in both groups compared with those before treatment(P＜0.05).Moreover,the magnitude of reduction in all these scores was significantly greater in the study group than that in the control group(P＜0.01).(3)After treatment,the VAS scores for pain severity decreased in both groups compared with baseline(P＜0.05),while the Harris scores for joint function increased in both groups(P＜0.05).Furthermore,the magnitude of reduction in VAS scores and the magnitude of improvement in Harris scores were both significantly greater in the study group than those in the control group(P＜0.01).(4)After treatment,plasma viscosity,high-shear whole blood viscosity,and low-shear whole blood viscosity decreased in both groups compared with those before treatment(P＜0.05).Additionally,the reductions in all these parameters were significantly more pronounced in the study group than in the control group(P＜0.01).(5)After treatment,serum alkaline phosphatase(ALP)levels decreased in both groups(P＜0.05),while serum osteocalcin(BGP)and bone morphogenetic protein-2(BMP-2)levels increased in both groups(P＜0.05).Crucially,the magnitude of reduction in serum ALP levels and the magnitude of elevation in serum BGP and BMP-2 levels were all significantly greater in the study group than those in the control group(P＜0.01).(6)After treatment,in the study group,the number of patients with Grade 3 muscle strength significantly decreased while the number with Grade 4 muscle strength significantly increased compared with those before treatment(P＜0.05).In contrast,although the control group showed some improvement in joint muscle strength,the changes were not statistically significant(P＞0.05).After treatment,the intergroup comparisons showed that the study group had a significantly smaller number of patients with Grade 3 muscle strength and a significantly larger number with Grade 4 muscle strength than the control group(P＜0.01).(7)After treatment,both local femoral head BMD and average BMD increased in both groups compared with those before treatment(P＜0.05).The magnitude of increase in both local and average BMD was significantly greater in the study group than that in the control group(P＜0.01).Conclusion The application of Taohong Siwu Decoction in the treatment of in patients after hip preservation surgery for ONFH is effective on reducing TCM syndrome scores,alleviating pain,improving joint function and hemorheology,and restoring BMD and bone metabolism indicators,which enhances the overall clinical efficacy for the patients.

Objective To explore the relationship between NANOS3 and P-bodies in oocytes and the mechanism of their interaction during early oogenesis.Methods The co-localization of NANOS3 and dead box helicase 6(DDX6)in day post postnatal 1(1dpp)mouse oocytes was observed by immunofluorescence,and the interaction between NANOS3 and DDX6 was detected by immunoprecipitation.NANOS3 and DDX6 full-length plasmids were constructed to transfect HEK293T cells,and the mechanism of their interaction was investigated by immunofluorescence and immunoprecipitation.NANOS3 transfected HeLa cells to investigate whether NANOS3 had the ability of liquid-liquid phase separation(LLPS)by live-cell imaging.The proteins recruited by P-bodies in early oogenesis were identified by DDX6-immunoprecipitation-mass spectrometry(DDX6-IP-MS).Results NANOS3 and DDX6 colocalized and interacted with each other in 1dpp mouse oocytes.However,the co-localization of NANOS3 and DDX6 was not observed in HEK293T cells that had been transfected,but co-immunoprecipitation still demonstrated an interaction between these two proteins.Besides,live-cell imaging revealed that NANOS3 exhibited dynamic fluid-like properties within cells,which may promote the formation of P-bodies through LLPS.Finally,DDX6-IP-MS revealed that DDX6 might recruit NANOS3 into P-bodies by binding to the NANOS3 interacting protein Pumilio.Conclusion NANOS3 serves as a specific component of P-bodies in neonatal oocytes and may be involved in the regulation of early oogenesis.

Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

The quality of traditional Chinese medicine(TCM) is a critical foundation for ensuring the stability of its efficacy, as well as the safety and effectiveness of its clinical use. The identification of critical quality attributes(CQAs) is one of the core components of TCM preparation quality control. This study focuses on Jianwei Xiaoshi Tablets and explores their CQAs related to property and flavor from the perspective of taste receptor proteins. Three taste receptor proteins, T1R2, T1R3, and TRPV1, were selected, and a biosensor based on high-electron-mobility transistor(HEMT) was constructed to detect the interactions between Jianwei Xiaoshi Tablets and taste receptor proteins. Simultaneously, liquid chromatography-mass spectrometry(LC-MS) technology was used to analyze the chemical composition of Jianwei Xiaoshi Tablets. In examining the interaction strength, the results indicated that the interaction between Jianwei Xiaoshi Tablets and TRPV1 protein was the strongest, followed by T1R3, with the interaction with T1R2 being relatively weaker. By combining biosensing technology with LC-MS, 16 chemical components were identified from Jianwei Xiaoshi Tablets, among which six were selected as CQAs for sweetness and seven for pungency. Further validation experiments demonstrated that CQAs such as hesperidin and hesperetin had strong interactions with their corresponding taste receptor proteins. Through the combined use of multiple technological approaches, this study successfully determined the property and flavor-related CQAs of Jianwei Xiaoshi Tablets. It provides novel ideas and approach for the identification of CQAs in TCM preparations and offers comprehensive theoretical support for TCM quality control, contributing to the improvement and development of TCM preparation quality control systems.
Drugs, Chinese Herbal/chemistry* ; Biosensing Techniques/methods* ; TRPV Cation Channels/chemistry* ; Tablets/chemistry* ; Receptors, G-Protein-Coupled/genetics* ; Quality Control ; Taste ; Humans ; Mass Spectrometry