BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

OBJECTIVE: To evaluate the effectiveness of double joystick technique assisted closed reduction and Kirschner wire internal fixation in the treatment of Gartland type Ⅲ supracondylar fractures of the humerus (SCFH) in children. METHODS: A retrospective study was conducted on 28 cases of Gartland type Ⅲ SCFH with complete data available, who underwent closed reduction and Kirschner wire internal fixation with the double joystick technique between August 2022 and July 2024. There were 23 boys and 5 girls, with an average age of 6.4 years (range, 1-12 years). All fractures resulted from falls and were classified as extension-type. X-ray film showed the radial displacement of the distal fragment in 15 cases and unlar displacement in 13 cases. The interval from injury to operation was 3-36 hours (mean, 19.5 hours). X-ray film re-examination was conducted to evaluate the fracture healing, and the Baumann angle of affected elbow joint and carrying angle of bilateral elbow joints were measured. Elbow joint function was evaluated using the range of motion (flexion and extension) and the Flynn criteria. The above indicators were compared between affected and healthy sides. RESULTS: All operation were successfully completed. The operation time ranged from 15 to 40 minutes (mean, 25.2 minutes). The length of hospital stay was 2-5 days (mean, 3.5 days). All patients were followed up 3-24 months (mean, 11.8 months). X-ray film confirmed fracture healing in all patients, with a mean healing time of 5.4 weeks (range, 4-6 weeks). At last follow-up, the Baumann angle of the affected elbow joint was (73.50±3.46)°, and the carrying angle and the range of motion in flexion and extension of the affected elbow joint were significantly less than the contralateral side (P<0.05). According to the Flynn criteria, the elbow joint function of the affected elbow was evaluated as excellent in 25 cases and good in 3 cases, with an excellent and good rate of 100%. CONCLUSION The double joystick technique is a safe and effective method which can facilitate the closed reduction and Kirschner wire internal fixation of Gartland type Ⅲ SCFH in children without increasing risk of complications.
Humans ; Male ; Female ; Humeral Fractures/diagnostic imaging* ; Fracture Fixation, Internal/instrumentation* ; Child ; Retrospective Studies ; Bone Wires ; Child, Preschool ; Fracture Healing ; Treatment Outcome ; Infant ; Elbow Joint/physiopathology* ; Range of Motion, Articular ; Closed Fracture Reduction/methods*

OBJECTIVE: To investigate the short-and med-term clinical efficacy of unicompartmental knee arthroplasty(UKA)for the treatment of medial knee osteoarthritis (OA) in elderly patients with anterior cruciate ligament deficiency(ACLD). METHODS: A retrospective analysis was conducted on 31 patients aged over 75 years old with primary medial knee OA and ACLD who underwent UKA between January 2018 and December 2022. The cohort included 12 males and 19 females, aged from 75 to 91 years with an average age of (79.56±4.54) years, with 13 left knee, 16 right knee, and 2 bilateral knees. Clinical outcomes were assessed preoperatively and at final follow-up using the visual analogue scale (VAS), Hospital for Special Surgery(HSS) score, range of motion (ROM), hip-knee-ankle angle (HKA), and tibial component posterior slope angle (TCPSA). Complications such as infection, prosthesis wear, prosthesis loosening, and dislocation were also recorded. RESULTS: All 31 patients were followed up from 12 to 63 months with an average of (28.34±10.56) months. The average postoperative TCPSA was (4.83±1.31)° ranged from 2.5° to 6.8°. At the final follow-up, there was significant improvement in VAS (3.24±0.53) vs. (6.59±0.69), HSS score (85.19±4.45) vs. (64.38±5.94), ROM (118.83±5.38)° vs. (98.85±4.08)°, and HKA (176.83±5.16)° vs. (169.57±6.28)° compared to preoperative values (P<0.05). No cases of infection, prosthesis loosening, or dislocation were reported. CONCLUSION UKA provides favorable short-and mid-term outcomes for elderly patients with medial knee OA and ACLD . However, long-term clinical efficacy needs further investigation through extended follow-up.
Humans ; Male ; Female ; Arthroplasty, Replacement, Knee/methods* ; Aged ; Osteoarthritis, Knee/physiopathology* ; Retrospective Studies ; Aged, 80 and over ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/surgery*

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Objective To observe the clinical efficacy of oral use combined with targeted transdermal delivery of Osteoking in treating knee osteoarthritis(KOA)of cold-damp blockage type.Methods A total of 120 patients with KOA of cold-damp blockage type who admitted to Hunan Provincial Hospital of Integrated Traditional Chinese And West Medicine from September 2022 to September 2023 were randomly divided into the control group,oral use group,transdermal delivery group and combination group according to the random number table method,with 30 cases in each group.The control group was treated with Celecoxib Capsule orally,the oral use group was treated with Osteoking orally,the transdermal delivery group was treated with Osteoking by targeted transdermal delivery,and the combination group was treated with oral use combined with targeted transdermal delivery of Osteoking.One course of treatment covered 12 days,and all of the four groups were treated for two continuous courses.Before and after treatment,the scores of traditional Chinese medicine(TCM)syndrome,Visual Analogue Scale(VAS)for pain,Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)for joint function,36-Item Short Form Health Survey(SF-36)for quality of life(QOL),as well as the levels of serum interleukin 1β(IL-1β),interleukin 6(IL-6),and tumor necrosis factor α(TNF-α)were observed in the patients of each group.After treatment,the clinical efficacy and safety of patients in each group were evaluated.Results(1)After two courses of treatment,the total effective rate of the combination group was 96.67%(29/30),which was higher than those of the control group[73.33%(22/30)],oral use group and transdermal delivery group[both being 70.00%(21/30)],and the difference was statistically significant(P<0.05).However,no statistically significant difference of the total effective rate was presented among the control group,oral use group,and transdermal delivery group(P>0.05).(2)After treatment,the scores of TCM syndrome,VAS for pain and WOMAC for joint function in the four groups were decreased compared with those before treatment(P<0.01).The intergroup comparison showed that the scores of TCM syndrome,VAS for pain and WOMAC in the combination group were lower than those in the other three groups(P<0.05),while no statistically significant difference of the scores of TCM syndrome,VAS for pain and WOMAC were presented among the control group,oral use group,and transdermal delivery group(P>0.05).(3)After treatment,the QOL scores of the eight dimensions of SF-36 such as physical functioning(PF),bodily pain(BP),general health(GH),vitality(VT),role-physical(RP),social functioning(SF),role-emotional(RE),and mental health(MH)in the four groups were significantly increased compared with those before treatment(P<0.01).The intergroup comparison showed that the scores of each dimension of SF-36 in the combination group were significantly higher than those in the other three groups(P<0.05),while no statistically significant difference of the dimension score of SF-36 was presented among the control group,oral use group,and transdermal delivery group(P>0.05).(4)After treatment,the levels of serum inflammatory factors of IL-1β,IL-6,and TNF-α in the four groups were decreased compared with those before treatment(P<0.01).The intergroup comparison showed that the decrease of serum levels of inflammatory factors in the combination group were significantly superior to those in the other three groups(P<0.05),and the decrease in the control group and oral use group were all superior to those in the transdermal delivery group(P<0.05),while the difference between the control group and oral use group was not statistically significant(P>0.05).(5)During the trial,no serious adverse reactions were found in the patients of four groups,which is of high safety.Conclusion Oral use combined with targeted transdermal delivery of Osteoking is effective on improving the joint pain,joint function and QOL of patients with KOA of cold-damp blockage type,and can speed up the rehabilitation of patients.Its therapeutic mechanism may be related to the decrease of the expression level of inflammatory factors.

OBJECTIVE: To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma. METHODS: In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously. RESULTS: In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01). CONCLUSIONS Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity* ; Animals ; Humans ; NAD(P)H Dehydrogenase (Quinone)/genetics* ; HEK293 Cells ; Kidney/pathology* ; Cytochrome P-450 CYP1A2/genetics* ; Mice, Inbred C57BL ; DNA Adducts/drug effects* ; Male ; Kidney Diseases/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Prunus armeniaca ; Plant Extracts

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 effect and safety of pancreatic extracorporeal shock wave lithotripsy (P-ESWL) in treating the chronic pancreatitis (CP) patients with main pancreatic duct (MPD) stones and to analyze the influencing factors of success of lithotripsy.Methods:Clinical data of 132 patients with CP complicated with MPD stones treated with P-ESWL in the Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2022 to December 2023 were retrospectively analyzed, including 103 males and 29 females, aged (50.3±16.9) years. The times of P-ESWL, the success rate of stone fragmentation, the necessity of combining endoscopic retrograde cholangiopancreatograhy (ERCP), clearance rate of MPD stones, and incidence of post-P-ESWL complications (acute pancreatitis, abdominal hematoma, infection, steinstrasse, perforation, etc.) were evaluated. The factors influencing the success rate of lithotripsy were analyzed using univariate and multivariate logistic regression.Results:All patients underwent P-ESWL treatment, with (2.23±0.82) times of P-ESWL per person. The success rate of stone fragmentation was 87.1%(115/132). Of 107 CP patients (81.1%, 107/132) were treated with their first P-ESWL. Of 12 patients (9.1%, 12/132) underwent single P-ESWL, and 120 (90.9%, 120/132) underwent P-ESWL combined with ERCP. There were 95 cases (72.0%, 95/132) with effective removal of stones, and 62 (47.0%, 62/132) with complete removal of stones. Post-P-ESWL complications included eight cases (6.1%, 8/132) of acute pancreatitis, two (7.6%, 2/132) of steinstrasse complicated with acute pancreatitis and one (0.8%, 1/132) of abdominal hematoma. No infection or perforation occurred. Multivariate logistic regression analysis showed that the higher CT value of stones ( OR=1.239, 95% CI: 1.040-1.477, P=0.017) was associated with the lower success rate of stone fragmentation. Conclusion:P-ESWL is safe and effective in treating patients with CP complicated with MPD stones. The CT value of stones is a risk factor for the success rate of P-ESWL.

Objective To explore the impact of peptidylarginine deiminase 2(Padi2)-knockout on depressive-like behaviors in socially isolated mice.Methods Using CRISPR/Cas9 technology,a Padi2-knockout(Padi2-/-)mouse model with a C57BL/6J background was established,and the effect of Padi2 knockout was identified by genotyping and RT-qPCR detection.Six-week-old male Padi2-/- mice and wild-type C57BL/6J mice were selected and divided into normal rearing and social isolation groups,with 15 mice per group.The normal rearing group mice were housed with 5 mice per cage,and the social isolation group was housed with 1 mouse per cage,and weighed once a week.After 4 weeks,forced swimming and open field tests were conducted.After the behavioral experiments,brain tissues were taken from mice in each group,and changes in microglia in the brains were detected by immunofluorescence.Results We successfully established Padi2-/- mice.There was no difference in behavior between Padi2-/- mice and C57BL/6J mice in the normal rearing group.After social isolation,compared with C57BL/6J mice,Padi2-/- mice showed a significant increase in depressive symptoms,obvious weight gain,and a significant increase in the number of microglia in brain tissue.Conclusions Padi2 knockout exacerbated depressive-like behaviors and obesity in socially isolated mice,indicating that Padi2 is involved in the progression of depression and may be an effective target for the prevention and treatment of depression.