[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Autoimmunity and the activation of immune cells are closely related to the occurrence of chronic spontaneous urticaria, while the gut microbiota participates in multiple physiological activities including the regulation of the host's immunity. Gut microbiota in patients with chronic spontaneous urticaria has unique structural composition and metabolic features. Gut microbiota imbalance and secondary short-chain fatty acid deficiency may be important causes for the occurrence of the disease and aggravation of inflammation. Studies have shown that probiotics can improve the clinical manifestations of patients with urticaria. This review summarizes the research progress in the correlations of gut microbiota and short-chain fatty acids with chronic spontaneous urticaria.

Objective:To investigate the long-term prognosis and related factors in children with multiphasic myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).Methods:A bidirectional cohort study was conducted. This study included 41 children with MOGAD who were treated at the Children′s Medical Center of Peking University First Hospital between January 2013 and December 2024, with a disease duration of ≥5 years. Demographic characteristics, clinical episodes, therapy, and prognostic indicators (including the expanded disability status scale (EDSS) and modified Rankin scale (mRS)) were collected. Children were stratified into relapse and non-relapse groups based on the presence or absence of relapse within 5 years of the last follow-up. χ2 test or Mann-Whitney U test was used to analyze factors associated with relapse. The Log-rank test was used to compare relapse-free rates between children with disease onset 0-<5 years and those with onset at 5-10 years. Results:A total of 41 children were enrolled, including 20 boys and 21 girls. The age at onset was 5.3 (3.8, 8.5) years, the age at last follow-up was 16.1 (13.2, 17.5) years, and the disease duration was 9.4 (8.1, 10.9) years. The annualized relapse rate (ARR) during follow-up was 0.34 (0.19, 0.56) times/year. The duration to first relapse was 0.8 (0.4, 1.5) years. At the last follow-up, the EDSS score was 0.0 (0.0, 0.0) score, and the mRS score was 0 (0, 0) score. A total of 40 children (98%) experienced relapses within the first 5 years after onset, while only 1 child (2%) relapsed at 6.7 years. The relapse rate between 5-10 years was lower than that between 0-<5 years ( HR=0.27, 95% CI 0.16-0.47, P<0.001). A total of 25 children (61.0%) exhibited clustered relapses during the disease course. There were 20 children (49%) in non-relapse groups, who were aged 16.6 (14.8, 17.6) years, disease duration 9.8 (9.3, 10.8) years at the last follow-up. Among those 20 children, 15 children (75%) had discontinued corticosteroids and immunosuppressants. The relapse group had higher clinical event rates and ARR compared to the relapse-free group (both P<0.01), the age at last follow-up was yonger ( P<0.05), while no significant differences were observed in age at onset, disease duration, or timing of immunosuppressant use (all P>0.05). Conclusions:Pediatric multiphasic MOGAD generally has a favorable prognosis, about half of patients remain relapse-free for ≥5 years at last follow-up. Relapses predominantly occur early in the disease course (mostly within 5 years of onset) and often exhibit a clustered pattern.

BACKGROUND:Studies have found that massage can reduce blood sugar,promote myogenic factor expression,and increase skeletal muscle content.The extracellular matrix is an important component of skeletal muscle,and association between massage and extracellular matrix and their mechanism of action are still unclear.OBJECTIVE:To explore the effect of massage on extracellular matrix collagen deposition in type 2 diabetic sarcopenia rats.METHODS:Totally 24 Wistar male rats were randomly divided into blank group,model group,and massage group.High-fat diet combined with the streptozotocin method was used to establish a type 2 diabetes mellitus and sarcopenia model.After successful model establishment,the massage group used abdominal massage combined with hind limbs.After 8 weeks of treatment,the fasting blood glucose and serum insulin levels of the rats were measured.The skeletal muscle mass was detected by dual-energy X-ray.The exhaustion time was measured by small animal treadmill.The sliding angle was measured by inclined board test.The pathological changes of skeletal muscle tissue were observed by hematoxylin-eosin staining.The skeletal muscle collagen deposition was observed by Masson staining.The mRNA and protein expressions of type Ⅰ and type Ⅲ collagen in skeletal muscle were detected by qPCR and western blot assay.RESULTS AND CONCLUSION:(1)Compared with the model group,the blood glucose(P＜0.05)and serum insulin(P＜0.01)decreased in the massage group.(2)Compared with the model group,the skeletal muscle mass,running exhaustion time,and the angle of inclined plate experiment were increased in massage group(P＜0.05).(3)Compared with the model group,the skeletal muscles of the massage group were arranged neatly,muscle atrophy was improved,and collagen fiber deposition was reduced.(4)Compared with the model group,the expression levels of type Ⅰ and type Ⅲ collagen mRNA and protein in skeletal muscle were decreased in the massage group(P＜0.05).(5)The results suggest that massage can enhance insulin sensitivity,lower blood sugar,improve skeletal muscle mass,strength and function,and diminish collagen deposition in rats with type 2 diabetes,and may be a potential target for massage to exert its therapeutic effects.

Objective·To explore the roles of hyaluronic acid methacryloyl(HAMA)hydrogel in skin wound healing and to characterize the microenvironmental landscape at wound sites.Methods·A full-thickness skin excision model was established in mice,which were randomly divided into a control group(n=3)and a HAMA group(n=3).The wound in the HAMA and control groups were covered with 100 μL of HAMA hydrogel and 100 μL of phenyl-2,4,6-trimethylbenzoylphosphonic acid lithium(LAP),respectively.Both groups were then irradiated with a UV lamp for 20 s.The residual wound areas was measured on days 0,3,7,10,and 14.Wound healing effects of HAMA hydrogel were analyzed by measuring the residual wound area and through H-E staining.Single-cell RNA sequencing technology was utilized to analyze the cellular profile of local wound skin tissues at day 14 post-injury.Immunofluorescence assay was used to detect the levels of type I collagen,type Ⅲ collagen,F4/80,CD206,and CD86 in the wound sites.The mRNA expression levels of Arg1,Nos2,Itgam,and Itgb2 in the mouse macrophage cell line Raw264.7 co-cultured with HAMA hydrogel for 24 h were detected by RT-qPCR.The fibroblasts and macrophages in the local skin of the mouse wound on day 14 were analyzed using the Seurat package,and the communication between fibroblasts and macrophages was analyzed using the CellChat package.Results·Mice treated with HAMA hydrogel exhibited a significantly faster rate of wound healing process compared to the control group.At day 14,wounds in the HAMA-treated mice had already healed,while those in the control group remained unhealed.Single-cell RNA sequencing analysis revealed a remarkable increase in the proportion of fibroblasts in the skin tissues of HAMA-treated wounds.The proportion of the Col3a1-high-expressing fibroblast subset increased(90.2%)compared to the control group(79.8%),while the proportion of the Col1a1-high-expressing fibroblast subset decreased(5.7%vs 15.9%).Immunofluorescence analysis confirmed that the level of type Ⅲ collagen in the wound tissues of the HAMA group was significantly higher than that in the control group(P=0.035),while the level of type Ⅰ collagen was significantly lower(P=0.044).Although there was no significant difference in the proportions of macrophages in the wound tissues between the HAMA-treated and control groups,scRNA sequencing data and in vitro experiments using Raw264.7 cells showed that HAMA hydrogel could induce the expression of Arg1 and decrease the expression of Nos2 in the macrophages(P<0.001).Additionally,macrophages in the HAMA-treated wounds expressed higher levels of CD206 and lower levels of CD86(P=0.042,P=0.011).The results of the CellChat analysis showed that,compared to the control group,increased communication intensity was observed between macrophages and fibroblasts subsets at the wound sites in the mice of HAMA group.Conclusion·The microenvironment after HAMA hydrogel treatment is conducive to skin wound healing,characterized by a local aggregation of anti-inflammatory macrophages and fibroblasts that secrete type Ⅲ collagen.

Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.

Autoimmunity and the activation of immune cells are closely related to the occurrence of chronic spontaneous urticaria, while the gut microbiota participates in multiple physiological activities including the regulation of the host's immunity. Gut microbiota in patients with chronic spontaneous urticaria has unique structural composition and metabolic features. Gut microbiota imbalance and secondary short-chain fatty acid deficiency may be important causes for the occurrence of the disease and aggravation of inflammation. Studies have shown that probiotics can improve the clinical manifestations of patients with urticaria. This review summarizes the research progress in the correlations of gut microbiota and short-chain fatty acids with chronic spontaneous urticaria.

Objective To explore the efficacy and safety of one-stage flexible ureteroscopic lithotripsy for bilateral kidney stones.Methods Retrospectively analyzed 112 patients with bilateral kidney stones treated by flexible ureteroscopic lithotripsy from January 2018 to October 2023.Based on the treatment procedure,the participants were divided into an observation group and a control group.The observation group(60 cases)underwent one-stage lithotripsy using flexible ureteroscopy for bilateral kidney stones,the control group(52 cases)received staged lithotripsy for bilateral kidney stones.The operation time,intraoperative blood loss,stone clearance rate one month after operation,postoperative hematuria time,duration of lumbar and abdominal pain,creatinine level one day after operation and incidence of postoperative complications were compared between the two groups of patients.Results Findings indicated that the observation group had a mean operation time of(103.68±27.46)min,which was significantly shorter compared to the control group's mean operation time of(132.51±39.74)min,the difference was statistically significant(P<0.01).Additionally,the stone clearance rate after one month post-operation was 91.67%in the observation group and 90.38%in the control group(P=0.920);The average blood loss of the observation group was(15.29±5.15)mL,and the duration of postoperative lumbar and abdominal pain was(6.18±1.40)d,while the average blood loss of the control group was(12.00±3.62)mL,and the duration of postoperative lumbar and abdominal pain was(4.56±1.12)d,with significant difference(P<0.01);The duration of postoperative hematuria in the observation group was(3.07±0.92)d,the incidence of postoperative irritation sign of bladder was 65.00%,the incidence of postoperative moderate and low fever was 25.00%,and the creatinine level on the first day after surgery was(73.47±17.80)μmol/L,while the duration of postoperative hematuria in the control group was(2.73±1.28)d,the incidence of postoperative irritation sign of bladder was 53.85%,the incidence of postoperative moderate and low fever was 17.31%,and the creatinine level on the first day after surgery was(68.61±17.38)μmol/L,the differences were not statistically significant(P>0.05).Conclusion One stage flexible ureteroscopic lithotripsy for bilateral kidney stones is safe and effective,moreover,the surgical outcome is close to that of staged surgery,but postoperative nursing and pain management should be strengthened in order to improve the effect of comprehensive treatment.

BACKGROUND:Studies have found that massage can reduce blood sugar,promote myogenic factor expression,and increase skeletal muscle content.The extracellular matrix is an important component of skeletal muscle,and association between massage and extracellular matrix and their mechanism of action are still unclear.OBJECTIVE:To explore the effect of massage on extracellular matrix collagen deposition in type 2 diabetic sarcopenia rats.METHODS:Totally 24 Wistar male rats were randomly divided into blank group,model group,and massage group.High-fat diet combined with the streptozotocin method was used to establish a type 2 diabetes mellitus and sarcopenia model.After successful model establishment,the massage group used abdominal massage combined with hind limbs.After 8 weeks of treatment,the fasting blood glucose and serum insulin levels of the rats were measured.The skeletal muscle mass was detected by dual-energy X-ray.The exhaustion time was measured by small animal treadmill.The sliding angle was measured by inclined board test.The pathological changes of skeletal muscle tissue were observed by hematoxylin-eosin staining.The skeletal muscle collagen deposition was observed by Masson staining.The mRNA and protein expressions of type Ⅰ and type Ⅲ collagen in skeletal muscle were detected by qPCR and western blot assay.RESULTS AND CONCLUSION:(1)Compared with the model group,the blood glucose(P＜0.05)and serum insulin(P＜0.01)decreased in the massage group.(2)Compared with the model group,the skeletal muscle mass,running exhaustion time,and the angle of inclined plate experiment were increased in massage group(P＜0.05).(3)Compared with the model group,the skeletal muscles of the massage group were arranged neatly,muscle atrophy was improved,and collagen fiber deposition was reduced.(4)Compared with the model group,the expression levels of type Ⅰ and type Ⅲ collagen mRNA and protein in skeletal muscle were decreased in the massage group(P＜0.05).(5)The results suggest that massage can enhance insulin sensitivity,lower blood sugar,improve skeletal muscle mass,strength and function,and diminish collagen deposition in rats with type 2 diabetes,and may be a potential target for massage to exert its therapeutic effects.