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 analyze the high risk factors of obstetric brachial plexus palsy(OBPP),and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification.Methods A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center.The shortcomings of hospitals in birth weight assessment,delivery mode selection,labor process observation and shoulder dystocia management,and the causal relation-ship between them and the damage consequences of the children were summarized.Results Fault medi-cal behavior was assessed as the primary cause in 2 cases,equal cause in 10 cases,secondary cause in 8 cases,minor cause in 1 case,no causal relationship in 1 case,and unclear causal force in 3 cases.Conclusion In the process of forensic identification of OBPP,whether medical behaviors fulfill diagno-sis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation,de-livery mode notification,standardized use of oxytocin,standard operation of shoulder dystocia,etc.Meanwhile,it is necessary to fully consider the objective risk of different risk factors and the diffi-culty of injury prevention,and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

Hepatitis B virus (HBV) infection is a serious global public health problem. Chronic hepatitis B virus infection can cause health problems such as cirrhosis, liver metabolism disorders and hepatocellular carcinoma. Nucloes(t)ide analogues and interferon drugs used to treat chronic HBV infection do not completely eradicate covalently closed circular DNA (cccDNA) and integrated genome of HBV DNA, so that they cannot achieve the functional cure of chronic HBV infection. Currently, a series of drugs targeting the phases of HBV lifecycle and immunomodulators have entered clinical trials. Here, we review the current status of the therapeutic drugs as well as the recent advance of direct antiviral agents.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Oligoasthenoteratozoospermia (OAT) refers to the combination of various sperm abnormalities, including a decreased sperm count, reduced motility, and abnormal sperm morphology. Only a few genetic causes have been shown to be associated with OAT. Herein, we identified a novel homozygous frameshift mutation in meiosis-specific nuclear structural 1 (MNS1; NM_018365: c.603_604insG: p.Lys202Glufs*6) by whole-exome sequencing in an OAT proband from a consanguineous Chinese family. Subsequent variant screening identified four additional heterozygous MNS1 variants in 6/219 infertile individuals with oligoasthenospermia, but no MNS1 variants were observed among 223 fertile controls. Immunostaining analysis showed MNS1 to be normally located in the whole-sperm flagella, but was absent in the proband's sperm. Expression analysis by Western blot also confirmed that MNS1 was absent in the proband's sperm. Abnormal flagellum morphology and ultrastructural disturbances in outer doublet microtubules were observed in the proband's sperm. A total of three intracytoplasmic sperm injection cycles were carried out for the proband's wife, but they all failed to lead to a successful pregnancy. Overall, this is the first study to report a loss-of-function mutation in MNS1 causing OAT in a Han Chinese patient.

OBJECTIVE: To compare the effect of electroacupuncture preconditioning with different frequencies on anal pain after milligan-morgan hemorrhoidectomy. METHODS: A total of 120 patients with mixed hemorrhoids were randomly divided into an electroacupuncture group A (dilatational wave, 2 Hz/100 Hz in frequency), an electroacupuncture group B (continuous wave, 2 Hz in frequency) and an electroacupuncture group C (continuous wave, 100 Hz in frequency), 40 cases in each group. Electroacupuncture at Xialiao (BL 34) and Chengshan (BL 57) was applied with tolerant intensity for 30 min before operation in all groups. The number of additional anesthetic drugs in the 3 groups, the visual anal pain score (VAS) and limb activity score at 4, 12, and 24 h after operation, the maximum VAS score within 24 h after surgery and oral dose of aminophenol dihydrocodeine were compared. RESULTS: The number of additional anesthetic drugs in the electroacupuncture group A, the electroacupuncture group B and the electroacupuncture group C were 4, 5, 4 respectively, and there was not statistically significant (>0.05). There was no significant difference in the anal pain VAS score and limb activity score at 4 h after operation among the 3 groups (>0.05), at the 12 h after operation, the VAS scores and limb activity scores in the electroacupunctures group A and B were lower than those in the electroacupuncture group C (<0.05), at 24 h after operation, the VAS score and limb activity score in the electroacupuncture group A were lower than those in the electroacupuncture group B and C (<0.05), the maximum VAS score within 24 h and oral dose of aminophenol dihydrocodeine within 24 h after operation in the electroacupuncture group A were lower than those in the electroacupuncture group B and C (<0.05). CONCLUSION Different frequency electroacupuncture preconditioning has the effect of alleviating anal pain after milligan-morgan hemorrhoidectomy. The analgesic effect of electroacupuncture with different frequencies is different. The electroacupuncture analgesic effect of 2 Hz /100 Hz dilatational wave is better than 2 Hz and 100 Hz continuous waves.
Anal Canal ; Electroacupuncture ; Hemorrhoidectomy ; Hemorrhoids ; therapy ; Humans ; Pelvic Pain

OBJECTIVE: To investigate the effect of electroacupuncture preconditioning combined with induced urination on urinary retention after milligan-morgan hemorrhoidectomy. METHODS: Eighty patients with mixed hemorrhoids were randomly divided into an electroacupuncture group and a routine group, 40 cases in each group. Anesthesia at Yaoshu (GV 2) was given in the two groups. In the electroacupuncture group, electroacupuncture at Zhongji (CV 3)，Guanyuan (CV 4)，Pangguangshu (BL 28) and Sanyinjiao (SP 6) was applied with tolerant intensity for 30 min before operation, 2 Hz/100 Hz in frequency. After operation, induced urination was given, namely hot compress of bladder area and sound of hearing water. In the routine group，induced urination was given after operation. The score of the first urination waiting time, the distension of lower abdomen on the evening of the postoperative, the first time urinary volume and incidence of urinary retention were compared between the two groups. RESULTS: The scores of the first urination waiting time after operation and distension of lower abdomen in the evening of the postoperative in the electroacupuncture group were lower than those in the routine group, the first time urinary volume was more than that in the routine group, and the incidence of urinary retention was lower than that in the routine group (5.0% (2/40) vs 22.5% (9/40), all <0.05). CONCLUSION Electroacupuncture preconditioning combined with induced urination can effectively prevent the incidence of urinary retention after milligan-morgan hemorrhoidectomy.
Electroacupuncture ; Hemorrhoidectomy ; Hemorrhoids ; Humans ; Urinary Retention ; therapy ; Urination

Liver injury remains a significant global health problem and has a variety of causes, including oxidative stress (OS), inflammation, and apoptosis of liver cells. There is currently no curative therapy for this disorder. Sanwei Ganjiang Prescription (SWGJP), derived from traditional Chinese medicine (TCM), has shown its effectiveness in long-term liver damage therapy, although the underlying molecular mechanisms are still not fully understood. To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view, in the present study, a systems pharmacology approach was developed, which involved drug target identification and multilevel data integration analysis. Using a comprehensive systems approach, we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets. We further deciphered the mechanisms of SWGJP in treating liver injury, including compound-target network analysis, target-function network analysis, and integrated pathways analysis. We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway, such as Nrf2-dependent anti-oxidative stress module. Notably, systems pharmacology provides an alternative way to investigate the complex action mode of TCM.
Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Expression ; drug effects ; Hepatocytes ; drug effects ; metabolism ; Humans ; Liver ; drug effects ; injuries ; metabolism ; Liver Diseases ; drug therapy ; genetics ; metabolism ; Oxidative Stress ; drug effects ; Pharmacology

OBJECTIVEOn the basis of western medication, to investigate the effect of electroacupuncture (EA) combined with auricular point sticking therapy for anal pain of mixed hemorrhoid after external excision and internal ligation，so as to explore the method of improving its effect.

METHODSNinety patients of mixed hemorrhoids who received external excision and internal ligation were randomly assigned into an EA group, an auricular point sticking group and a combined group, 30 cases in each one. All the treatment was applied 30 min before surgery. Electroacupuncture was used at Xialiao (BL 34) and Changqiang (GV 1) in the EA group, once a day. The auricular points were bilateral shenmen (TF), pizhixia (AT), jiaogan (AH) and gangmen (HX) in the auricular point sticking group, pressing 3-6 times every day, once 3-5 min. EA and auricular point sticking therapy were applied in the combined group. When the visual analogue scale (VAS) score was above 6, aminophenol dihydrocodeine was applied in the three groups. The scores of anal pain VAS and limb activity at the 4th, 12th, 24th, 48th, 72th hours after operation were compared among the three groups, as well as the maximum scores of VAS in 24 hours (T24max VAS) of 1-3 days after operation, the total dose of aminophenol dihydrocodeine 72 h after operation.

RESULTSThe VAS and limb activity scores at all the time points after operation, the T24max VAS on the 1st, 2nd and 3rd days after operation and the dose of aminophenol dihydrocodeine in the combined group were better than those in the EA and auricular point sticking groups (all <0.05). The VAS and limb activity scores at 4, 12, 24 h after operation and T24max VAS on the 1st day after operation in the EA group were lower than those in the auricularpoint sticking group (all <0.05). The VAS and limb activity scores at 48, 72 h after operation, and the T24max VAS on the 2nd and 3rd days in the auricular point sticking group were lower than those in the EA group (all <0.05).

CONCLUSIONEA combined with auricular point sticking therapy are better than simple EA and auricular point sticking therapy for anal pain of mixed hemorrhoid after external excision and internal ligation. The analgesic effect of EA is rapider, and the effect of auricular point sticking therapy is longer. The combination of the two methods own coordination effect.

Objective To explore the role of Notch signaling pathway in the matrix synthesis of osteoarthritis cartilage cell and its possi -ble mechanism.Methods Selected the femoral condylar cartilage of 8 patients who were admitted into our hospital and treated with knee joint replacement as the observation group,while the normal femoral condyle cartilage of one patient with above-knee amputation was selected as the control group.The specimens were given histological examination or cell isolation culture and detection.The cultured cells were divided into 4 groups,namely the normal cartilage cells,OA cartilage cells,OA cartilage cells with γ-secretase inhibitor DAPT,OA cartilage cells with recombinant human proteins Delta4.Then immunohistochemistry and Western blot were used for detecting the expression of Notch -1,Notch-3, Jagged-1,Jagged-2 and HES5 in chondrocytes in vitro.Results The expression of Notch signaling pathway and the phenotype of cartilage cells changed in the osteoarthritis.The expression of Notch-1,Jagged-1,Jagged-2 and HES5 were activated.γ-secretase inhibitor DAPT (20 μmol/L)could inhibit the expression of Notch-1,HES5,Jagged-1,and Notch-3,while it had no obvious effect on the expreesion of Jag-ged-2.Recombinant human proteins Delta 4(100 ng/μL)could promote the expression of Notch-1,Jagged-2,and HES5,and it had no obvi-ous effect on the expreesion of Jagged-1 and Notch-3.Conclusion The expression of Notch signaling pathway of cartilage cells changed in the osteoarthritis.DLL4 can activate the Notch signaling pathway and DAPT can inhibit the Notch signaling pathway.