Objective:To summarize the clinical treatment of complete left bundle branch block (CLBBB) after the transcatheter closure of ventricular septal defect (VSD).Methods:A case series study was conducted on the treatments and outcomes of 25 children with CLBBB after transcatheter VSD closure in Guangdong Provincial People′s Hospital from January 2010 to December 2023.Paired sample t test was used to evaluate the effect of occlude removal. Results:Among the 25 patients, 12 were males (48%), and 13 were females (52%).The age at surgery was 3.18 (2.51-3.86) years, the height before surgery was 95.0 (90.0-97.5) cm, and the weight before surgery was 13 (12-15) kg.Fourteen children were early-onset cases (≤ 1 month), while the other 11 were late-onset cases (> 1 month).The mean follow-up time was (6.63±3.93) years.Of the 14 early-onset cases, 6 children underwent occluder removal within 1 month and restored normal heart rhythm or incomplete right bundle branch block; 4 children underwent occluder removal after 1 month, of whom 2 recovered, 1 remained CLBBB, and 1 had complete atrioventricular block (CAVB); the other 4 children received drug treatment, of whom 2 had normal heart rhythm, 1 had left anterior fascicular block, and 1 died of cardiac shock and heart failure.All the 11 late-onset cases were first treated by drugs, of whom 3 recovered, and the other 8 remained CLBBB.One of the 8 cases received occluder removal at 8 months after surgery and recovered, 1 had CAVB, and the other 6 remained CLBBB.Conclusions:For patients with CLBBB after transcatheter closure of VSD, drug therapy is not always effective, and CLBBB is easy to recur.Therefore, occluder removal is recommended to be done immediately after CLBBB is discovered.Patients with persistent CLBBB should be followed up regularly, and pacemaker implantation may be performed if necessary.

Objective:To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL).Methods:A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children′s Hospital, Capital Medical University and Baoding Children′s Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients.Results:Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) ( χ2=1.88, 1.47, P=0.170, 0.224). Conclusions:Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Objective To explore the clinical value of endoscopic ultrasonography(EUS)combined with serum serine protease inhibitor Kazal 1(SPINK1)and secretory phosphoprotein 1(SPP1)in early diagnosis of esophageal cancer.Methods 276 patients from June 2021 to May 2023 were selected as the study objects.92 cases of esophageal cancer diagnosed by operation and pathology were esophageal cancer group,another 89 patients diagnosed as benign esophageal lesions through tissue biopsy were selected as the benign lesion group,and 95 healthy individuals who underwent physical examinations were collected as the healthy control group,general information such as age and gender of subjects in three groups were collected and organized;using pathological results as the gold standard,the accuracy of EUS in diagnosing esophageal cancer was verified;the expression of serum SPINK1 and SPP1 was compared among the esophageal cancer group,benign lesion group,and healthy control group;the relationship between the expression of serum SPINK1 and SPP1 in esophageal cancer patients and their clinical and pathological characteristics was explored;efficacy of EUS combined with serum SPINK1,SPP1 levels for early diagnosis of esophageal cancer was analyzed using receiver operator characteristic curve(ROC curve).Results Compared with the gold standard,the results of EUS examination showed that 81 cases were diagnosed with esophageal cancer,79 cases were diagnosed with benign lesions,11 cases were missed diagnosed,and 10 cases were misdiagnosed,with an accuracy rate of 88.40%(160/181);Compared with the healthy control group and the benign lesion group,the expression levels of serum SPINK1 and SPP1 in the esophageal cancer group were obviously increased,the expression levels of serum SPINK1 and SPP1 in the benign lesion group were significantly higher than those in the healthy control group,the differences were statistically significant(P<0.05);Serum SPINK1 expression was linked to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and tissue grading level 3 in patients(P<0.05).Serum SPP1 expression level was related to tumor diameter>2 cm,presence of lymph node metastasis,lymph node positivity,and estrogen receptor positivity of patients(P<0.05);ROC curve showed that the area under the curve(AUC)of EUS,serum SPINK1,SPP1 levels,and their combination in the early diagnosis of esophageal cancer was 0.862,0.834,0.782,and 0.926,respectively,the clinical efficacy of the combination of the three in the early diagnosis of esophageal cancer was superior to that of EUS,serum SPINK1,and SPP1 alone(Z=2.30,Z=3.70,Z=4.23,P=0.022,P=0.000,P=0.000).Conclusion The expression levels of serum SPINK1 and SPP1 in esophageal cancer patients are abnormally up-regulated.The combination of EUS and serum SPINK1 and SPP1 has high clinical value in early diagnosis of esophageal cancer.

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of prurigo nodularis (PN) in the real world.Methods:PN patients who were subcutaneously injected with dupilumab for over 12 weeks were collected from the China Type Ⅱ Inflammatory Skin Disease Clinical Research and Standardized Diagnosis and Treatment Project Database from June 2021 to October 2022. Their clinical data were retrospectively analyzed, which included demographic data, and changes in pruritus numeric rating scale (NRS), investigator global assessment for PN-Stage (IGA PN-S), dermatology life quality index (DLQI) and hospital anxiety and depression scale (HADS) scores before and after treatment. Differences in scores before and after treatment, as well as in efficacy between patients with and without a history of atopic diseases, were analyzed using Wilcoxon signed-rank test, paired t-test or chi-square test. Results:A total of 66 PN patients were collected, including 42 males and 24 females, and they were aged 8 to 89 (44.12 ± 24.17) years. Thirty-six patients had a history of atopic diseases, and 27 had a family history of atopic diseases. After 12-week treatment with dupilumab, the pruritus NRS, IGA PN-S and DLQI scores in the 66 patients significantly decreased from the baseline scores (7.00 [5.00, 8.00], 3.00 [3.00, 4.00], 12.00 [7.75, 20.25], respectively) to 3.00 [2.00, 4.25], 2.00 [2.00, 3.00], 5.00 [1.75, 8.25], respectively (all P < 0.001). Among the 66 patients, 39 continued the regular treatment with dupilumab after 12 weeks and were followed up to 16 weeks; their pruritus NRS and IGA PN-S scores at week 16 further decreased compared with those at week 12 (both P < 0.05). There were no significant differences in the proportion of patients showing an improvement of ≥ 4 points in the NRS score or the proportion of patients achieving IGA 0/1 at week 12 between the patients with history of atopic diseases and those without (both P > 0.05). Before treatment, 32 PN patients were accompanied by mild to severe anxiety and/or depression; after 12-week treatment, the HADS-A scores in the 28 patients with anxiety (HADS-A scores > 7 points) and the HADS-D scores in the 20 patients with depression (HADS-D scores > 7 points) significantly decreased compared with their baseline scores (both P < 0.001) ; 18 (56.52%) patients achieved remission in anxiety and depression (both HADS-A and HADS-D scores < 7 points). Among the 66 PN patients, there were 13 minor patients, including 7 males and 6 females, and they were aged 8 to 17 (13.77 ± 3.09) years; after 12-week treatment, their pruritus NRS, IGA PN-S, and DLQI scores significantly decreased compared with the corresponding baseline scores (all P < 0.05) ; 8 minor patients continued dupilumab treatment for 16 weeks, with a further decrease in the IGA PN-S score compared with that at week 12 ( P < 0.05), but without significant differences between the pruritus NRS and DLQI scores at week 16 and those at week 12 (both P > 0.05). Adverse reactions were observed in 7 adult patients, including eye pruritus, local injection reactions, and systemic erythema accompanied by pruritus on the day of injection. No adverse reactions were reported in minor patients. Conclusion:In the real world, dupilumab could markedly alleviate pruritus, skin lesions, anxiety and depression symptoms in PN, improve the quality of life, and exhibited a good safety profile.

Objective:To investigate the long-term safety and effectiveness of stent implantation for residual pulmonary artery stenosis after complicated congenital heart disease.Methods:The symptoms, signs, echocardiography, cardiac CT, cardiac catheterization, six-minute walking distance, and BNP of 41 patients diagnosed from January 1996 to January 2020. In this group, 41 patients, 30 males and 11 females, aged 1.3-14.5 years old, mean (6.1±3.6) years old, and weighed 8-43 kg, mean (18.9±9.4)kg, compared the diameter of the target vessel, pressure difference across stenosis, cardiac function before and postoperative follow-up, and evaluated the long-term effect of stent implantation in the treatment of pulmonary artery stenosis.Results:All 41 patients were not lost to follow-up, no death, and there were no serious adverse events such as stent fracture, artery dissection and pulmonary embolism during follow-up. The median follow-up time was 7.1 years (3.1 to 13.8 years). As of January 2023, the echocardiographic results showed that the diameter of the target vessels in 41 patients increased from preoperative (3.9±1.5) mm to (6.0±1.5) mm ( P<0.05), the pressure difference across the stenosis decreased from preoperative (51.4±19.1) mmHg to (33.1±19.7) mmHg (1 mmHg=0.133 kPa, P<0.05); Heart spiral CT showed that the ratio of target vessel diameter to distal vessel diameter increased from preoperative 0.4±0.2 to 0.9±0.3( P<0.05). All patients had no slow growth and development, no recurrent lung infection, 39 patients (95.1%) had gradeⅠcardiac function, and 2 patients (4.9%) had gradeⅡcardiac function.As children in school age, the walking distance of 6 min was 462 to 633 m, mean( 529.9±57.1)m, the respiratory score was 0.5-1, and the lower limb force score was 6-12. There were 5 long-term adverse events, including 4 cases of target vessel restenosis (9.7%), and 1 case (2.4%), two of the patients with restenosis with repeated target vessel stenosis and lateral pulmonary hypertension were surgically intervention: stent removing and pumonary expanding, after 4, 13 years of stent implantation.And the others were still in follow-up, and no further intervention was made. The Cox multivariate survival analysis suggested that right ventricular systolic blood pressure was a risk factor for endpoint events before stent implantation ( P<0.05). Conclusion:The treatment of residual pulmonary artery stenosis after complicated congenital heart disease after percutaneous stent implantation can effectively relieve the right heart pressure overload, improve pulmonary blood flow, stabilize cardiac function, improve the long-term prognosis of patients with complicated congenital heart disease, reduce the chest opening rate of reoperation, and have stable long-term curative effect.

Objective:To explore the antipyretic effect and partial mechanism of the pushing Tianheshui manipulation on lipopolysaccharide(LPS)-induced fever in young New Zealand rabbits. Methods:Thirty 50-day-old New Zealand rabbits were randomly assigned to five groups,including a normal group,a model group,a Tuina(Chinese therapeutic massage)group,a Tuina control group,and a drug group,with 6 rabbits in each group.All groups except for the normal group received LPS injections through the marginal ear vein to induce fever.One hour post-modeling,the Tuina and Tuina control groups received pushing Tianheshui manipulation and pushing manipulation on the medial middle of the hind limbs,respectively,administered every hour for a total of 3 interventions.The drug group was given acetaminophen oral liquid via gavage.Anal temperature was recorded every 30 min for 4.0 h to monitor temperature changes among groups.At 4.0 h post-modeling,hypothalamus samples from each group were analyzed using Western blotting(WB)and real-time quantitative polymerase chain reaction(RT-qPCR)to measure the relative expression levels of α-melanocyte-stimulating hormone(α-MSH),melanocortin 4 receptor(MC4R),cyclic adenosine monophosphate(cAMP),protein kinase A(PKA),nuclear factor-κB p65(NF-κB p65),and interleukin(IL)-1β proteins and their mRNAs. Results:Compared to the model group,the Tuina group showed a significant reduction in the anal temperature from 3.5 h to 4.0 h post-modeling(P<0.05).The Tuina control group did not show a significant temperature reduction from 0.5 h to 4.0 h post-modeling(P>0.05).The drug group exhibited a significant temperature reduction from 1.5 h to 4.0 h post-modeling(P<0.05).At 4.0 h post-modeling,compared to the model group,the Tuina group showed significantly increased relative expression of α-MSH and MC4R proteins and mRNAs(P<0.05)and significantly decreased relative expression of cAMP,PKA,NF-κB p65,and IL-1β proteins and mRNAs in the hypothalamus tissue(P<0.05).No significant differences were observed in these parameters in the Tuina control group compared to the model group(P>0.05). Conclusion:Pushing Tianheshui manipulation demonstrated a significant antipyretic effect,potentially linked to point specificity.Its mechanism may involve the α-MSH-mediated cAMP/PKA/NF-κB pathway.

Objective To analyze the expressions of receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) in peripheral blood of neonates with necrotizing enterocolitis (NEC) and their relationships with the severity of the disease. Methods Ninety-two children with NEC were selected and divided into NEC group, and further divided into mild group (grade Ⅰ, n=60) and severe group (gradeⅡ to Ⅲ, n=32) according to the severity of the disease. Another 60 children with inguinal hernia were selected as control group. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expressions of RIPK3 mRNA and MLKL mRNA in peripheral blood. Pearson correlation analysis was used to determine the correlation between RIPK3 mRNA and MLKL mRNA expression in peripheral blood of the NEC group. Western blot was used to detect the expression of RIPK3 and MLKL proteins in ileal tissues of NEC and normal ileal tissues. Multivariate Logistic regression analysis was used to identify independent risk factors for severe NEC. The receiver operating characteristic curve was plotted to analyze the value of peripheral blood RIPK3 mRNA and MLKL mRNA alone and their combination for predicting severe NEC. Results The relative expression levels of RIPK3 mRNA and MLKL mRNA in peripheral blood of the NEC group were significantly higher than those in the control group[(2.41±0.52) versus (1.02±0.21), (3.03±0.64) versus (0.93±0.20), P < 0.001]. The relative gray values of RIPK3 and MLKL proteins in ileal tissues of NEC were significantly higher than those in normal ileal tissues[(1.20±0.21) versus (0.34±0.12), (1.13±0.24) versus (0.32±0.11), P < 0.05]. There was a positive correlation between the relative expression level of RIPK3 mRNA and MLKL mRNA in peripheral blood of children with NEC (r=0.623, P < 0.001). The proportion of children with severe NEC complicated by pneumoperitoneum, multiple organ dysfunction syndrome, and sepsis, as well as the relative expression levels of RIPK3 mRNA and MLKL mRNA were significantly higher in the severe NEC group than in the mild NEC group (P < 0.05). The relative expression levels of RIPK3 mRNA and MLKL mRNA were independent risk factors for severe NEC (P < 0.05). The area under the curve for combined prediction of severe NEC by RIPK3 mRNA and MLKL mRNA in peripheral blood was larger than that for individual prediction (Z=4.127, 4.261, P < 0.05). Conclusion The expression levels of RIPK3 mRNA and MLKL mRNA in peripheral blood are elevated in neonates with NEC, and both are associated with the severity of NEC. The combined detection of RIPK3 mRNA and MLKL mRNA has a higher predictive value for severe NEC.

Objective:To investigate the effects of abdominal Tuina(Chinese therapeutic massage)on behavioral function,5-hydroxytryptamine 1A receptor(5-HT1AR),and synapsin-1(Syn1)in neonatal rats with hypoxic-ischemic brain injuries(HIBI). Methods:Forty healthy neonatal rats,born of 5 specific pathogen-free healthy pregnant rats,were randomly divided into a group for modeling(n=28)and a sham operation group(n=12)on the 7th day of birth.In the group for modeling,24 neonatal rats with HIBI successfully established by the Rice method were randomly divided into a model group(n=12)and an abdominal Tuina group(n=12).The abdominal Tuina group was given abdominal Tuina for 28 d from 24 h after modeling,and the other groups were put under the same conditions but without any treatments.Rats in each group were subjected to suspension tests on the 7th,14th,21st,and 28th days of intervention.After the intervention,the rat hippocampal tissue was collected and stained with hematoxylin-eosin to observe the pathological changes in the rat hippocampal CA1 region.The 5-HT1AR expression in rat hippocampal CA1 region was detected by immune-histochemistry.The Syn1 expression in rat hippocampus was measured by Western blotting method. Results:The cells were disordered,and edema and necrosis appeared in the hippocampal CA1 region of the model group.Cell arrangement was clear,and edema was improved obviously in the hippocampal CA1 region of the abdominal Tuina group.Compared with the sham operation group,the suspension test scores,the number of 5-HT1AR positive cells,and Syn1 protein expression in the hippocampus decreased significantly in the model group after 21 d and 28 d of interventions(P<0.05).Compared with the model group,the suspension test scores,the number of 5-HT1AR positive cells,and Syn1 protein expression increased significantly in the abdominal Tuina group after 21 d and 28 d of interventions(P<0.05). Conclusion:Abdominal Tuina improves the behavioral function of upper limbs and up-regulates the expression levels of 5-HT1AR and Syn1 in the hippocampus of neonatal HIBI rats.

Objective:To compare the clinical efficacy and safety of single microneedle radiofrequency versus photodynamic therapy in the treatment of inflammatory lesions of moderate and severe facial acne vulgaris.Methods:Sixty patients with moderate to severe facial acne vulgaris were retrospectively collected from Guangzhou Institute of Dermatology between December 2021 and July 2022, including 30 patients who had received single microneedle radiofrequency treatment, and 30 patients who had received photodynamic therapy. There were no significant differences in the age, gender distribution, and severity of acne between the two groups (all P > 0.05). The patients in the microneedle radiofrequency group were treated with single microneedle radiofrequency once every 4 weeks for 2 sessions; those in the photodynamic therapy group received aminolevulinic acid-based photodynamic therapy once every 2 weeks for 3 sessions; patients in both groups were still treated with oral doxycycline for 8 weeks. After 8-week treatment, the efficacy, pain severity and incidence of adverse reactions were compared between the two groups. Statistical analysis was carried out by using chi-square test, two independent samples t-test and Mann-Whitney U test. Results:After 8-week treatment, there was no significant difference in the response rate between the microneedle radiofrequency group (93.33%, 28/30) and photodynamic therapy group (86.67%, 25/30; χ2 = 0.74, P = 0.389). No significant difference was observed in the pain severity score between the microneedle radiofrequency group (4.80 ± 2.08) and photodynamic therapy group (4.13 ± 1.86, t = 1.32, P = 0.194), and there was also no significant difference in the pain degree between the two groups ( Z = -1.13, P = 0.260). In the microneedle radiofrequency group, burning sensation occurred in 3 cases (10.00%), swelling and pain in 4 (13.33%), erythema in 2 (6.67%), and dryness and desquamation in 2 (6.67%), and no reactive acne or hyperpigmentation was observed; in the photodynamic therapy group, burning sensation occurred in 10 cases (33.33%), swelling and pain in 9 (30.00%), erythema in 8 (26.67%), reactive acne in 11 (36.67%), hyperpigmentation in 2 (6.67%), and dryness and desquamation in 11 (36.67%). Compared with the photodynamic therapy group, the microneedle radiofrequency group showed significantly decreased incidence rates of burning sensation, erythema, reactive acne, and dryness and desquamation ( χ2 = 4.81, 4.32, 13.47, 7.95, respectively, all P < 0.05) ; there was no significant difference in the incidence rates of swelling and pain as well as hyperpigmentation between the two groups ( χ2 = 2.46, 2.07, respectively, both P > 0.05) . Conclusion:Single microneedle radiofrequency showed marked efficacy equivalent to that of photodynamic therapy in the treatment of moderate to severe facial acne vulgaris, but higher safety, providing more clinical treatment options for moderate to severe facial acne vulgaris.

Minimally degenerative nephropathy is one of the common types of primary nephrotic syndrome, and it is currently believed that B lymphocytes are closely related to its pathogenesis. Patients with refractory small degenerative kidney disease require treatment with glucocorticoids combined with immunosuppressant. Rituximab is a monoclonal antibody that consumes B cells. Its use in the treatment of patients with refractory microdegenerative kidney disease can reduce recurrence rate, prolong remission period, and reduce hormone exposure. However, there is no consensus on the treatment plan and adverse reaction response measures, and multicenter, prospective, and large-scale research answers are still needed. This article summarizes the latest progress of rituximab in the treatment of refractory minimal degenerative kidney disease, hoping to provide assistance for the development of clinical treatment strategies.