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

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*

Licorice-gypsum (gancao-shigao, GC-SG) drug pair was used as the research object, using supramolecular chemistry to explore the scientific connotation of combining herbal medicine GC with insoluble mineral medicine SG in clinical application of traditional Chinese medicine. ① The Tyndall effect, microscopic morphology and particle size of the single and co-decocted of GC and SG were observed, the paste content and conductivity were determined, and the interaction between GC and SG was detected by isothermal titration calorimetry (ITC) and infrared absorption spectroscopy (IR). ② Calcium chloride (CaCl₂), a soluble calcium salt of equal gypsum quality, was used instead of SG with GC for co-decocting to explore the effect of calcium salt content on the water decocting, and the characteristics were combined with the Tyndall effect, microscopic morphology, paste content and conductivity. ITC and IR techniques were used to detect the interaction between the two, and the interaction between them was detected by ITC and IR. The zeta potential and ultraviolet-visible spectrophotometry (UV-vis) of GC-SG and GC-CaCl₂ co-decoction were compared, and the inorganic and organic components in the co-decoction were detected by inductively coupled plasma optical emission spectrometer (ICP-OES) and high performance liquid chromatography (HPLC). The results showed: ① Compared with the liquid phase of single decoction, GC-SG co-decoction had more obvious Tyndall effect, and showed uniform spherical nanoparticles under electron microscope. Physical characterization results such as paste content and conductivity showed that co-decoction promoted the dissolution of each other's components; ITC and IR results showed that there was strong interaction between GC and SG, which preliminatively indicated that GC and SG co-decoction promoted the formation of uniform and stable supramolecular system of traditional Chinese medicine. ② When soluble calcium salt was used to substitute insoluble SG with GC for co-decocting, a stronger but astigmatic light path appeared than single decocting solution, the zeta potential was reduced, and a large number of accumulated polymers were formed. The results of paste content and conductivity showed that the dissolution of the co-decocting component was reduced than the single decocting component. ITC, UV-vis and IR results showed that there was interaction between GC with Ca²⁺ and SG. The formation of polysink indicated that a large amount of soluble calcium salt would destroy the stability of supramolecular Chinese medicine. The results of ICP-OES and HPLC showed that the glycyrrhizic acid (GA) content of the former lower than the latter, which was related to the formation of a large number of polycondensates with the increase of Ca²⁺ concentration and the decrease of the dissolution of GA and other active ingredients. This study indicates that the compatibility of GC and SG can form a uniform and stable supramolecular system of traditional Chinese medicine. Calcium salt, the main component of SG, is taken as the starting point. Excessive soluble Ca²⁺ can promote the aggregation of active ingredients such as GA, so as to reveal the scientific connotation of the compatibility of GC and SG, an insoluble mineral medicine.

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

Objective: To compare the surgical outcome of robotic thyroidectomy through transoral approach and the bilateral breast-axillary approach. Methods: Retrospective analysis was made on the clinical data of patients who performed transoral robotic thyroidectomy (TORT group) or bilateral breast-axillary approach (BABA group) in the Department of Thyroid and Breast Surgery, the 960th Hospital of People's Liberation Army from July 2020 to May 2022. Both groups received lobectomy with lymph node dissection of the central region. A total of 100 cases were included in the study, including 48 cases in the TORT group and 52 cases in the BABA group. The propensity score matching method was used for 1∶1 matching of patients between the 2 groups, with a match tolerance of 0.03. There were 31 patients in each group successfully matched. In the TORT group, there were 5 males and 26 females, aged (33.2±7.9) years (range: 21 to 53 years). While there were 4 males and 27 females in the BABA group, aged (34.6±9.2) years (range: 19 to 58 years). The t test, Mann-Whitney U test, χ² test or Fisher exact test were used to compare the clinical efficacy between the two groups. Results: All the patients successfully completed robotic thyroid surgery without conversion to open surgery. Compared with BABA group, the TORT group had longer operation time ((211.3±57.2) minutes vs. (126.2±37.8) minutes, t=6.915, P<0.01), shorter drainage tube retention time ((5.4±1.0) days vs. (6.4±1.2) days, t=-3.544, P=0.001), shorter total hospital stay ((6.6±1.2) days vs. (7.4±1.3) days, t=-2.353, P=0.022), and higher cosmetic score (9.46±0.25 vs. 9.27±0.26, t=2.925, P=0.005). There was no significant difference between the two groups in the number of lymph nodes dissection, metastasis in the central compartment, and the incidence of postoperative complications (all P>0.05). Conclusions: Compared with the bilateral breast-axillary approach, the transoral vestibular approach of robotic thyroidectomy is also safe and effective. It shows similar surgical results to the bilateral breast-axillary approach in strictly selected patients, but the postoperative recovery speed is much faster, and the hospital stay is shorter. Transoral robotic thyroidectomy is a more recommended surgical method for patients with high aesthetic demand.
Male ; Female ; Humans ; Robotic Surgical Procedures/methods* ; Thyroid Neoplasms/surgery* ; Thyroidectomy/methods* ; Retrospective Studies ; Neck Dissection/methods* ; Axilla/pathology* ; Treatment Outcome

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q₁, Q₃) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q₁, Q₃) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans ; Male ; Middle Aged ; Young Adult ; Adult ; COVID-19/epidemiology* ; Incidence ; SARS-CoV-2 ; Logistic Models

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q₁, Q₃) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q₁, Q₃) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans ; Male ; Middle Aged ; Young Adult ; Adult ; COVID-19/epidemiology* ; Incidence ; SARS-CoV-2 ; Logistic Models

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.
Adult ; Aged ; Chromosome Aberrations ; Cytogenetics ; Female ; Humans ; Leukemia, Promyelocytic, Acute/genetics* ; Male ; Middle Aged ; Mutation ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult

OBJECTIVE: To recognize the spatial and temporal characteristics of iodine deficiency disorders (IDD), China national IDD surveillance data for the years of 1995-2018 were analyzed. METHODS: Time series analysis was used to describe and predict the IDD related indicators, and spatial analysis was used to analyze the spatial distribution of salt iodine levels. RESULTS: In China, the median urinary iodine concentration increased in 1995-1997, then decreased to adequate levels, and are expected to remain appropriate in 2019-2022. The goiter rate continually decreased and is expected to be maintained at a low level. Since 2002, the coverage rates of iodized salt and the consumption rates of qualified iodized salt (the percentage of qualified iodized salt in all tested salt) increased and began to decline in 2012; they are expected to continue to decrease. Spatial epidemiological analysis indicated a positive spatial correlation in 2016-2018 and revealed feature regarding the spatial distribution of salt related indicators in coastal areas and areas near iodine-excess areas. CONCLUSIONS Iodine nutrition in China showed gradual improvements. However, a recent decline has been observed in some areas following changes in the iodized salt supply in China. In the future, more regulations regarding salt management should be issued to strengthen IDD control and prevention measures, and avoid the recurrence of IDD.
China/epidemiology* ; Iodine ; Prevalence ; Sodium Chloride, Dietary ; Spatial Analysis ; Time Factors