Objective: To investigate the abnormal fluctuation of coagulation function indicators in pediatric Burkitt lymphoma patients, and to analyze its correlation with disease progression and prognosis. Methods: The data of 172 children with Burkitt lymphoma in Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2020 to December 2023 were retrospectively analyzed, and 120 healthy children were used as control group. Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), International standardized ratio (INR), D-dimer (D-D), fibrinogen degradation products (FDP), and antithrombin (AT) were measured. Appropriate statistical methods were used to compare the data between two groups, and the Cox regression model was employed to analyze the influencing factors. A P-value <0.05 was considered statistically significant. Results: Levels of D-D, FDP, INR, and PT were significantly higher in children with Burkitt lymphoma than in the healthy controls [median (P25, P75) for the case group: 0.35 (0.13, 1.22), 3.10 (1.30, 10.20), 1.16 (1.06, 1.24), 12.60 (11.43, 13.50); median (P25, P75) for the healthy control group: 0.10 (0.07, 0.15), 0.60 (0.20, 1.08), 1.06 (1.02, 1.13), 11.50 (11.00, 12.30)](P<0.05). Levels of D-D, FDP, INR, PT, and TT were significantly elevated in children with recurrence compared to those without recurrence [median (P25, P75) for the recurrent group: 0.44 (0.16, 1.42), 3.85 (1.50, 12.25), 1.17 (1.08, 1.24), 12.70 (11.73, 13.50), 16.20 (14.80, 17.80); median (P25, P75) for the non-recurrent group: 0.21 (0.11, 0.69), 2.00 (1.00, 6.85), 1.11 (1.03, 1.24), 11.90 (11.10, 13.43), 15.20 (14.50, 16.40)](P<0.05). Levels of D-D, FDP in children with metastasis were significantly higher than those without metastasis [median (P25, P75) for the metastatic group: 0.51 (0.17, 1.84), 4.38 (1.70, 13.45); median (P25, P75) for the non-metastatic group: 0.20 (0.11, 0.39), 1.50 (1.00, 3.10)] (P<0.05). Levels of D-D and FDP were significantly higher in children with advanced stage than in those with early stage [median (P25, P75) for the high-stage group: 0.33 (0.14, 1.20), 3.10 (1.40, 10.23); median (P25, P75) for the low-stage group: 0.12 (0.08, 0.24), 0.90 (0.50, 2.50)] (P<0.05). Levels of D-D and FDP in high-risk children were significantly higher than those of low-risk [median (P25, P75) for the high-risk group: 0.28 (0.13, 1.01), 2.90 (1.15, 9.65); median (P25, P75) for the low-risk group: 0.12 (0.08, 0.17), 0.80 (0.43, 1.98)] (P<0.05). Levels of D-D, FDP, INR, and PT were significantly higher in children with poor prognosis than in those with favorable prognosis [median (P25, P75) for the poor prognosis group: 1.76 (0.80, 2.72), 13.45 (7.20, 25.30), 1.19 (1.12, 1.32), 12.85 (12.10, 14.35); median (P25, P75) for the favorable prognosis group: 0.23 (0.12, 0.52), 2.00 (1.00, 4.80), 1.14 (1.05, 1.23), 12.30 (11.40, 13.40)] (P<0.05). INR levels significantly increased with accumulating chemotherapy cycles [median (P25, P75) for one session: 1.09 (1.02, 1.20); two sessions: 1.31 (1.23, 1.38); three sessions: 1.79 (1.52, 2.41)] (P<0.05). Age, APTT, D-D, FDP, INR, PT, recurrence and metastasis had a significant effect on the survival of children with Burkitt lymphoma (P<0.05). Conclusion: Patients with Burkitt lymphoma exhibit coagulation disorders, which are influenced by recurrence, metastasis, clinical stage, risk stratification, and prognosis. In clinical practice, it is crucial to prioritize the monitoring of coagulation indicators to facilitate timely detection of coagulation dysfunction.

OBJECTIVE: To observe the clinical efficacy of Daoqi (directing qi flowing) acupuncture technique in Huangdi Neijing (Yellow Emperor's Inner Classic) for moderate-to-severe obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Sixty patients with moderate-to-severe OSAHS were randomly divided into a Daoqi acupuncture group (30 cases) and a conventional acupuncture group (30 cases, 1 case dropped out). In the Daoqi acupuncture group, Daoqi acupuncture technique in Huangdi Neijing was applied at Shanglianquan (Extra), Fengfu (GV16), and bilateral Lieque (LU7), Zhaohai (KI6); in the conventional acupuncture group, conventional acupuncture was applied at Shanglianquan (Extra), Fengfu (GV16), Yamen (GV15), and bilateral Lieque (LU7), Zhaohai (KI6), Zusanli (ST36), Fenglong (ST40). The treatment was adopted once every other day, 3 times a week, 4 weeks as one course and 3 courses were required totally in both groups. Before and after treatment, the polysomnography (PSG) indexes [apnea-hypopnea index (AHI), hypopnea index (HI), apnea index (AI), longest apnea duration, lowest nocturnal SaO₂ (LSaO₂)], and scores of Epworth sleepiness scale (ESS), Pittsburgh sleep quality index (PSQI), World Health Organization quality of life-BREF (WHOQOL-BREF) were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the AHI, HI, AI and longest apnea duration were reduced compared with those before treatment in the two groups (P<0.01), the LSaO₂ was increased in the Daoqi acupuncture group (P<0.01); in the Daoqi acupuncture group, the AHI, HI, AI and longest apnea duration were lower than those in the conventional acupuncture group (P<0.05), and the LSaO₂ was higher than that in the conventional acupuncture group (P<0.05). After treatment, the ESS and PSQI scores were decreased compared with those before treatment (P<0.01), while the WHOQOL-BREF scores were increased compared with those before treatment (P<0.01) in the two groups; in the Daoqi acupuncture group, the ESS and PSQI scores were lower than those in the conventional acupuncture group (P<0.05, P<0.01), and the WHOQOL-BREF score was higher than that in the conventional acupuncture group (P<0.05). The total effective rate was 93.3% (28/30) in the Daoqi acupuncture group, which was higher than 82.8% (24/29) in the conventional acupuncture group (P<0.01). CONCLUSION Daoqi acupuncture technique in Huangdi Neijing can effectively treat moderate-to-severe OSAHS patients, improve the clinical symptoms and quality of life, and has the advantages i.e. simpler acupoints selection and gentler stimulation.
Humans ; Sleep Apnea, Obstructive/physiopathology* ; Male ; Female ; Middle Aged ; Acupuncture Therapy ; Adult ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Protein arginine methyltransferase 5 (PRMT5) exhibits elevated expression levels in a variety of cancers and has emerged as a critical target for cancer therapy in recent years. However, first-generation PRMT5 inhibitors have exhibited inadequate selectivity, leading to significant hematological toxicity, thus limiting their clinical utility. The second-generation PRMT5 inhibitors have shown marked improvement in safety and efficacy by selectively targeting MTAP-null tumor cells without impacting normal cells. This review systematically summarizes the biological and functional roles of PRMT5 in MTAP-deficient tumor cells, and comprehensively analyzes the research and development process, molecular binding mechanisms, and the latest advancements in clinical trials of the five second-generation PRMT5 inhibitors currently under investigation, aiming to provide valuable insights for further in-depth studies in this field.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.

Objective:To investigate the impact of air pollution on dynamic changes in lung function and further explore the association between genetic factors and lung function and its changes.Methods:Research data were from 14 506 participants in the United Kingdom Biobank with two complete baseline and follow-up lung function tests. Particulate matter [including particulate matter with aerodynamic diameter ≤2.5 μm and ≤10 μm (PM 2.5 and PM 10)], nitrogen dioxide (NO 2), and nitrogen oxides (NO x) concentrations were estimated using land-use regression models. Annual changes in lung function were calculated based on baseline and follow-up lung function tests. Polygenic risk scores (PRS) of lung function [forced expiratory volume in the first second (FEV 1), forced vital capacity (FVC), and the ratio of FEV 1 to FVC (FEV 1/FVC)] were constructed by genetic variations. The association between air pollution concentrations and lung function changes was analyzed by multiple linear regression models, and the impact of genetic factors on lung function and its changes was also assessed. Results:PM 2.5, PM 10, NO 2, and NO x showed a negative correlation with FVC changes [PM 2.5: -6.66 (95% CI: -9.92- -3.40) ml/year; PM 10: -0.40 (95% CI: -0.77- -0.03) ml/year; NO 2: -1.84 (95% CI: -2.60- -1.07) ml/year; NO x: -1.37 (95% CI: -2.27- -0.46) ml/year]. Additionally, PM 2.5, PM 10and NO 2 were also negatively correlated with changes in FEV 1 [PM 2.5: -3.19 (95% CI: -5.79- -0.59) ml/year; PM 10: -3.00 (95% CI: -5.92- -0.08) ml/year; NO 2: -0.95 (95% CI: -1.56- -0.34) ml/year]. PRS of lung function were positively correlated with baseline lung function (FVC, FEV 1, and FEV 1/FVC) and lung function changes (all β>0, all P<0.001). In different PRS stratification analyses, the effect of air pollution on lung function changes remained significant, and there was no apparent heterogeneity. Conclusions:PRS of lung function are significantly associated with baseline and lung function changes. Long-term exposure to air pollution accelerates the decline of lung function indicators such as FVC and FEV 1. The effects of air pollution are consistent in individuals with different genetic risk scores.

Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.

Objective:To evaluate the initial clinical outcome of applying a comprehensive debulking procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle to reconstruct the hypertrophic toes and forefoots in one-stage surgery in multiple toes macrodactyly in children.Methods:The clinical data of children with macrodactyly deformity treated by the Department of Burn and Plastic Surgery in Children’s Hospital of Chongqing Medical University from January 2022 to October 2023 were retrospectively analyzed. Design toe and plantar arbitrary flaps with a few vascular perforating branches which pedicle at the comparatively healthy proximal side and resect all tissues beyond the normal length. In severe toe, a composite tissue nail-flap with the artery was dissected to reconstruct the toenail. Fat debulking on the surface of deep plantar fascia as well as within the osseofascial sheath, resecting partially of the fatty infiltrated nerve, transverse and longitudinal osteotomy to shorten and narrowed phalanxes without epiphyseal block, arthroplasty and flexor tendon tightening were performed. Finally, toes shaped by wrapping toe flaps, and pelmas restored by plantar flaps which both with comparatively healthy proximal pedicle. The operation time, healing time, and whether the toes and toenails are preserved were all recorded. The maximum circumference of both foot, the difference in shoe size, the presence of skin ulcers, wound scars, toe webbing morphology, the presence of basic sensation, and the satisfaction of parents were followed-up after surgery. The modified follow-up questionnaire was used to evaluate the surgical effect, the total score is 0-12 points, and the higher the score, the better the surgical outcome. Descriptive methods was used for statistical analysis, and the measurement data conforming to normal distribution were expressed as Mean±SD.Results:A total of 15 patients were enrolled, including 11 males and 4 females. The median age at the time of operation was 2.75 years (0.9-10.8 years). There were 11 cases with 2 toes and 4 cases with 3 toes, a total of 34 toes involved. The average surgical duration was 4.13 hours (3.25 hours for 2 toes and 5.00 hours for 3 toes). Only one severe case with 3 toes involved was amputated the biggest toe ray and totally 2 toe nail flaps were harvested unsuccessfully intraoperative. Except 3 toes had distal skin partially necrosis and 2 nail flaps were completely necrotic which healed after dressing changes, the rest of the toes were healing well after operation. The average follow-up time was 4.8 months (3-11 months), the difference of circumference was less than 1.5 cm, as well as in length was less than 0.5 cm between feet and all children were able to wear the appropriate shoes with same size. A total of 4 toes failed to retain toenails, and 1 had a very thin toenail. Except for one case with insufficient web depth, the other toe webs were close to normal. There was no skin ulcer occurred, the basic sensation of the feet was present, and wound scars were inconspicuous. The score of the modified questionnaire was 10.54±0.88, all parents were satisfied with the results.Conclusion:Comprehensive procedure centered on the digital and plantar flaps with comparatively healthy proximal pedicle for debulking multiple toes macrodactyly in children could completely excise distal hypertrophic tissues in a single operation, and the size of the affected feet and toes can be greatly reduced to wearing shoes of the same size, and have a high success rate in preserving the toes, as well as nails. The reconstructed feet, toes and toe webbing have near-normal morphology, hidden scar, no ulcers after walked and achieve a good initial effect.

Objective To observe the correlations of chest CT quantitative parameters in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with blood eosinophil(EOS)level.Methods Chest CT data of 162 AECOPD patients with elevated eosinophils were retrospectively analyzed.The patients were divided into low EOS group(n=105)and high EOS group(n=57)according to the absolute counting of blood EOS.The quantitative CT parameters,including the number of whole lung bronchi and the volume of blood vessels,low-attenuation area percentage(LAA％)of whole lung,of left/right lung and each lobe of lung,as well as the luminal diameter(LD),wall thickness(WT),wall area(WA)and WA percentage of total bronchial cross-section(WA％)of grade 3 to 8 bronchi were compared between groups.Spearman correlations were performed to analyze the correlations of quantitative CT parameters with blood EOS level.Results LAA％of the whole lung,of the left/right lung and each lobe of lung,as well as of the upper lobe of right lung LDgrade4,middle lobe of right lung WTgrade5,upper lobe of right lung WAgrade4,middle lobe of right lung WAgrade5 and lower lobe of left lung WAgrade3 in low EOS group were all higher than those in high EOS group(all P＜0.05).Except for the upper lobe of right lung LDgrade4,the above quantitative CT indexes being significant different between groups were all weakly and negatively correlated with blood EOS level(r=-0.335 to-0.164,all P＜0.05).Conclusion Chest CT quantitative parameters of AECOPD patients were correlated with blood EOS level,among which LAA％,a part of WT and WA were all weakly negatively correlated with blood EOS level.