Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Ulcerative colitis is a chronic,non-specific inflammatory disease.The persistent damage to its intestinal epithelium is key to the development of the disease.In recent years,a new form of cell death has been identified by researchers-iron death-which is thought to be an important contributor to intestinal epithelial cell death.The occurrence of iron death is often associated with abnormal intracellular iron metabolism,reduced cystine/glutamate reverse transporter activity,abnormal lipid metabolism,voltage-dependent anion channel activation and overexpression of the Nrf2 gene.Iron death can lead to smaller mitochondria,increased membrane density and reduced number of cristae,unlike conventional cell death,which does not exhibit specific phenomena.Studies have found that TCM can alleviate iron death in intestinal epithelial cells by reducing intracellular iron content,inhibiting lipid reactive oxygen species production and regulating Nrf2 gene expression,thus acting as a treatment for ulcerative colitis.Therefore,Chinese medicine may become an important tool for the treatment of ulcerative colitis.This paper reviews the relationship between cellular iron death and ulcerative colitis and the research progress of Chinese medicine in treating ulcerative colitis through the iron death pathway.

Objective To discuss the curative effect of interventional embolization using vascular plug together with spring coil in treating varicocele.Methods A total of 15 patients with varicocele,who were admitted to authors'hospital between March 2022 and October 2022 to receive treatment,were enrolled in this study.Interventional embolization therapy by using vascular plug together with spring coil via the left elbow vein access or via the femoral vein access was carried out in all the 15 patients.The instant surgical success rate,complications,time spent for operation,average hospital stay,and postoperative clinical efficacy were recorded and analyzed.Results Successful interventional embolization using vascular plug together with spring coil was accomplished in all the 15 patients,and no complications occurred during the perioperative period.The time spent for operation was(19±12)min,and the average hospital stay was 2.3 days.The patients were followed up for one month,the degree of the scrotal varices was obviously improved,and the swelling feeling of the perineum was significantly reduced.Conclusion For the treatment of varicocele,the interventional embolization using vascular plug together with spring coil carries certain advantages,such as reliable curative effect,easy to operate,patient being more comfortable,fast recovery,and less complications.Therefore,this technique is a therapeutic approach worth further investigation.(J Intervent Radiol,2024,32:73-76)

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To summarize the clinical features associated with respiratory syncytial virus (RSV) infection in patients following the hematopoietic stem cell transplant (HSCT) and exploring the risk factors for death.Methods:Patients who had RSV infection after undergoing HSCT from October 2023 to January 2024 in the hematology department of Peking University People’s Hospital were enrolled in the study. The clinical characteristics of the participating patients were summarized. The clinical characteristics of the surviving and the dying patients were compared, and the risk factors of death were analyzed by binary logistic regression.Results:Among the 43 RSV-positive HSCT patients, 20 (46.5%) were hypoxemic, six (14.0%) were admitted to the ICU for further treatment, four (9.3%) required tracheal intubation assisted ventilation, and seven patients (16.3%) died. A comparison of the clinical features of the surviving patients and the deceased patients demonstrated that the deceased patients had a lower PLT when infected with RSV [74.5 (8.0-348.0) ×10 9/L vs 15.0 (10.0-62.0) ×10 9/L, P=0.003], a higher incidence of simultaneous bacterial infections (85.7% vs 41.7%, P=0.046), and a higher rate of hematological recurrence (71.4% vs 13.9%, P=0.004). Hematological recurrence ( OR=15.500, 95% CI 2.336-102.848, P=0.005), influenza A viral infection ( OR=14.000, 95% CI 1.064-184.182, P=0.045), and low PLT at the time of RSV infection ( OR=0.945, 95% CI 0.894-0.999, P=0.048) were the factors associated with death following HSCT. Conclusion:Patients infected with RSV after undergoing HSCT have a poor prognosis, and active prevention and treatment of RSV in the autumn and winter requires urgent attention.

Objective:To evaluate the clinical efficacy of intermittent theta burst stimulation (iTBS) of the bilateral cerebellum in treating post-stroke dysphagia.Methods:Forty patients with dysphagia after a cerebral infarction were randomly divided into a control group and an iTBS group, with 20 cases in each group. In addition to routine swallowing rehabilitation training and nutritional guidance, the iTBS group underwent daily bilateral cerebellar iTBS 6 times a week for 3 weeks, while the control group was given sham stimulation. Before and after the treatment, both groups were evaluated by using the water-swallowing test and the standardized swallowing assessment (SSA), and the latency and amplitude of the mylohyoid muscle′s motor evoked potential (MEP) were also recorded. The SSA scores and MEP amplitudes of the mylohyoid muscle after treatment were tested for any correlation.Results:The treatment improved the water-swallowing test results in both groups, with that of the iTBS group significantly better than that of the control group. The clinical efficacy in the iTBS group was 95%, significantly higher than the control group′s 80%. The SSA scores decreased significantly in both groups after the treatment, with the iTBS group′s average score then significantly lower than that of the control group. The average latency and amplitude of the mylohyoid muscle′s MEP was also significantly better in the iTBS group after the treatment. In the control group only the average amplitude was significantly greater than before the treatment. Pearson correlation analysis showed that the SSA scores and the MEP amplitudes of the mylohyoid muscle after treatment were uncorrelated in both groups.Conclusions:Bilateral intermittent theta burst stimulation can effectively improve the swallowing of patients with post-stroke dysphagia.

Femoral neck fracture (FNF) in the elderly patients is currently a major health challenge worldwide, with excessive consumption of medical resources, high incidence of complications as well as suboptimal outcome and prognosis. Hip joint arthroplasty (HJA) has been the mainstream treatment for FNF in the elderly, but the conventional surgical approaches and techniques are still confronted with a series of bottlenecks such as dislocation, limp and limb length discrepancy. In recent years, direct anterior approach (DAA) for HJA (DAA-HJA) has been a major new choice in the field of joint replacement, which achieves improved clinical effectiveness of HJA in the treatment of elderly FNF, due to the fact that DAA approach involves the neuromuscular interface and accords with the idea of soft tissue retention and enhanced recovery after surgery. However, there is still a lack of unified understanding of standard technique and procedure of DAA-HJA in the treatment of elderly FNF. Therefore, relevant experts from the Hip Joint Group of Chinese Orthopedics Association of Chinese Medical Association, Youth Arthrology Group of Orthopedic Committee of PLA, Orthopedic Committee of Chongqing Medical Association, Branch of Orthopedic Surgeons of Chongqing Medical Doctor Association and Sport Medicine Committee of Chongqing Medical Association were organized to formulate the " Chinese expert consensus on the technical standard of direct anterior hip arthroplasty for elderly femoral neck fracture ( version 2023)" based on evidence-based medicine. This consensus mainly proposed 13 recommendations covering indications, surgical plans, prosthesis selections, surgical techniques and processes, and postoperative management of DAA-HJA in elderly patients with FNF, aiming to promote standardized, systematic and patient-specific diagnosis and treatment to improve the functional prognosis of the patients.

Objective:To seek any differential effect of combining repeated transcranial magnetic stimulation (rTMS) with a modified version of constraint-induced movement therapy (mCIMT) on the walking ability of stroke survivors.Methods:Seventy-five stroke survivors were randomly divided into a sham rTMS group, an rTMS group and a combined group, each of 25. In addition to 40 minutes of routine rehabilitation daily, including balance training, transfer training, muscle strength training, and proprioceptive training five times a week for 4 weeks, the sham rTMS group and rTMS group received sham or genuine rTMS. The combined group received 20 minutes of rTMS followed by mCIMT training 30 minutes later. The treatment was performed once a day, 5 days a week for 4 weeks. Before and after the treatment, all groups were evaluated using the Fugl-Meyer lower extremity assessment, the Berg balance scale, a 10-metre walk test and the modified Barthel index.Results:Significant improvement was observed in the average scores of all three groups in all of the assessments. The combined group′s averages were, however, significantly better than those of the other two groups.Conclusion:Supplementing mCIMT with rTMS can better improve the walking and other abilities in the activities of daily living of stroke survivors.

BACKGROUND: Preliminary researches conformed that neoadjuvant immunotherapy combined with chemotherapy had a significant short-term effect in resectable non-small cell lung cancer (NSCLC), but there were few clinical trials about neoadjuvant chemoimmunotherapy in China. We aimed to assess retrospectively the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage Ib-IIIb NSCLC. METHODS: Twenty patients who had been diagnosed as stage Ib-IIIb NSCLC and received chemoimmunotherapy as neoadjuvant treatment between November 2019 and December 2020, in Beijing Chest Hospital, Capital Medical University were recruited. These patients received neoadjuvant treatment for 21 days as a cycle and antitumour activity and safety were evaluated every two cycles. RESULTS: Of 20 patients received neoadjuvant chemoimmunotherapy, 17 patients underwent surgical resection. 16 patients had R0 resection (no residual tumor resection) and 1 patient had R1 resection (microscopic residual tumor resection). Radiographic objective response rate (ORR) was 85.0% (4 complete response, 13 partial response). 5.0% (1/20) of patients had stable disease, and 10.0% (2/20) of patients had progression disease. The major pathologic response (MPR) was 47.1% (8/17), and complete pathologic response (CPR) was 29.4% (5/17). 1 case developed grade IV immune-related pneumonia (IRP) and 9 (45.0%) cases had grade III hematologic toxicity. CONCLUSIONS Immunotherapy combined with chemotherapy as neoadjuvant therapy has a better efficiency and tolerable adverse effects for patients with resectable NSCLC in stage Ib-IIIb.