Objective To explore the relationship between the volume and function of the heart and the pathogenesis of vasovagol syncope (VVS) through the detection of the left atrial volume index(LAVI).Methods The 68 cases in the observation group were diagnosed as VVS and hospitalized in the First Hospital of Jilin University from Jan.1 to Dec.31 in 2012.The 60 cases in the control group were children and adolescents receiving healthy physical examinations during the same period.All the patients were given the examination of heart color Doppler ultrasound,head up tilt test(HUT),body height,body mass,chest X-ray and accounted the LAVI and cardiothoracic ratio was accounted.Results The average age in the observation group and the control group was(12.19 ± 2.01) and(12.15 ± 2.00) years old,respectively.And there was no statistically significant difference in age between these two groups (t =0.10,P ＞0.05).There were 23 boys and 45 girls in the observation group,and 31 boys and 29 girls in the control group.There was statistically significant difference in the ratio of gender composition between these two groups (x2 =4.16,P ＜ 0.05).The LAVI values in these two groups were (21.23 ± 2.04) mL/m2 and (23.45 ± 3.01) mL/m2,respectively.There was statistically significant difference between two groups(t =4.29,P ＜ 0.05).The LAVI values in VVS mixed inhibition (VVS-MI),VVS vascular inhibition (VVS-VI) and VVS cardiac inhibition (VVS-CI) were (21.41 ± 2.98) mL/m2,(21.06 ± 2.59) mL/m2 and(21.23 ± 3.22) mL/m2,respectively.There were statistically significant differences between VVS-MI or VVS-VI and the control groups(t =3.27,3.36,all P ＜ 0.05),but there was no statistically significant difference between VVS-CI and control groups(t =1.61,P ＞ 0.05).The cardiothoracic ratio were 0.43 ± 0.07 and 0.46 ± 0.06 in the observation group and the control group,respectively,and there was statistically significant difference between these two groups(t =3.05,P ＜0.05).Conclusions The pathogenesis of VVS is related to the size and function of left heart.The children and adolescents with smaller LAVI and cardiothoracic ratio are more susceptible to VVS.

Objective To investigate the effects of Gegenqinlian Decoction on the IL-1β level in the patients with chronic periodontitis.Methods Seventy patients with chronic periodontitis were divided into the observation group and control group,35 cases in each group.The control group was given the periodontal basic treatment.On the basis of the control group,the observation group was given Gegenqinlian Decoction.The probing depth,attachment level and bacterial plaque index level before and after treatment were compared between the two groups.The levels of IL-1β and IL-6 in serum and gingival crevicular fluid were measured before and after treatment in the two groups.Results The total effective rate in the observation group was 94.29%,which was significantly higher than 71.43% in the control group,the difference was statistically significant (χ2=6.437,P<0.05).After treatment,the probing depth,attachment level and bacterial plaque index in the two groups were significantly decreased (P<0.05),but which in the observation group were significantly lower than those in the control group,the difference was statistically significant (P<0.05).The levels of IL-1β and IL-6 in serum and gingival crevicular fluid after treatment in the two groups were decreased significantly (P<0.05),but which in the observation group were significantly lower than those in the control group,the difference was statistically significant (P<0.05).Conclusion Gegenqinlian decoction can significantly reduce the IL-1β level in the patients with chronic periodontitis,reduces inflammation reaction and improves the therapeutic effect.

Objective:To explore the differences of renal dynamic imaging parameters between operation group and non-operation group in infants with severe hydronephrosis, so as to accumulate theoretical basis for diuretic renal scintigraphy to help the treatment decision making.Methods:A total of 107 infants (age: 3(2, 6) months; 90 males and 17 females) with severe hydronephrosis, who underwent diuretic renal scintigraphy between March 2018 and October 2021 in Shanxi Children′s Hospital were retrospectively reviewed. All patients were diagnosed with ureteropelvic junction obstruction and divided into operation group ( n=87) and no-operation group ( n=20). The differences of differential renal function (DRF), peak time, half-time and drainage curve between the two groups were compared with the independent-sample t test or χ2 test, and the correlation between the renal function of the affected side and the anteroposterior pelvic diameter (APD) was analyzed with Pearson correlation analysis. Results:The operation group included 17 patients with DRF<40%, 60 patients with DRF between 40%-55%, and 10 patients with DRF>55%(supernormal renal function). The 40%-55% was considered as normal DBF, and the rest were abnormal. Infants with abnormal renal function in the operation group ( n=27) were more than those in the non-operation group ( n=3), but there was no statistical difference ( χ2=2.07, P=0.150). The proportion of obstruction curve in the operation group (85.1%, 74/87) was significantly higher than that in the non-operation group (55.0%, 11/20; χ2=7.24, P=0.007). Compared with the non-operation group, the peak time of affected kidney in the operation group was significantly longer ((22.77±7.52) vs (15.26±10.29) min; t=3.78, P<0.001), as well as the peak time of contralateral kidney ((11.25±8.47) vs (6.65±5.75) min; t=2.30, P=0.023). There was a negative correlation between the DRF of the affected side and the APD ( r=-0.48, P<0.001). Conclusions:The DBF is mostly in the normal range in infants with severe hydronephrosis, and supernormal renal function is common. The previous operation indication (DRF<40%) is not suitable for the infants, and it needs to be analyzed combined with the type of curve and the APD determined by color Doppler ultrasound. The prolongation of contralateral renal peak time may be an important parameter for the surgical evaluation of severe hydronephrosis in infants.

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

Objective:To explore the clinical manifestations and genetic basis for a rare case of Generalized arterial calcification of infancy (GACI).Methods:A 44-day-old female infant who was treated at Baoding Hospital of Beijing Children′s Hospital Affiliated to Capital Medical University on August 26, 2022 was selected as the study subject. Clinical data of the child was collected, and Trio-whole exome sequencing (Trio-WES), whole genome copy number variation sequencing (CNV-seq) and minigene splicing assay were carried out to analyze the pathogenicity of the variants.Results:The child had presented with fever and high inflammatory indicators, for which treatment with various antibiotics was ineffective. Ultrasound had revealed extensive arterial calcification and arterial wall thickening. The child was suspected for GACI with arteritis related to the primary disease. Her fever was relieved by treatment with glucocorticoid and biological agents. Trio-WES revealed that she has harbored compound heterozygous variants of the ABCC6 gene, namely c. 4404-1G>A and c. 4041+ 5G>T, for which the latter was unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics, the variants were classified as likely pathogenic (PVS1+ PM2_Supporting) and variant of unknown significance (PM2_Supporting+ PM3+ PP3), respectively. The result of CNV-seq was negative. And the minigene splicing assay has further verified that both variants can result in alternative splicing. Conclusion:For pyrexia with unknown causes and refractory to conventional treatment, it is necessary to recommend early genetic testing to avoid missed diagnosis of GACI.

Radical prostatectomy(RP)was commonly used in localized prostate cancer. For patients with adverse pathological features (APF) after RP, it was controversial about choosing adjuvant radiotherapy or salvage radiotherapy (SRT). Recent studies have found that early salvage radiotherapy(ESRT) had both the same cancer control and reduced overtreatment compared to adjuvant radiotherapy. Nomogram and Gene Classifier(GC) could predict the risk of recurrence after RP and contribute to choose adjuvant radiotherapy or ESRT. PSMA PET/CT was more sensitive to detect distant metastasis after biochemical recurrence, which was helpful to decide whether to implement SRT.

Alanyl-glutamine dipeptide is an important component in parenteral nutrition, which can be decomposed into alanine and L-glutamine in vivo. It plays multiple functions including maintaining intestinal barrier, improving immunity, promoting protein synthesis, and regulating the production and release of inflammatory mediators. Substantial clinical evidences have demonstrated its favorable effectiveness and safety. Rational application of alanyl-glutamine dipeptide can reduce postoperative complications, shorten hospital stay and save medical costs. There are still controversies at home and abroad on the applicable population and dosage of alanyl-glutamine dipeptide. Chinese Society of Parenteral and Enteral Nutrition organized China's experts of related disciplines to compile international standards in accordance with the latest guidelines and consensus, so as to achieve the goal of standardized application and patient benefits.

BACKGROUND:Inflammation affects the osteogenic differentiation of periodontal ligament stem cells,and the osteogenic ability and autophagy level of periodontal ligament stem cells are closely related.However,there are no relevant reports on whether inflammation affects the osteogenic ability and autophagy level of periodontal ligament stem cells at different stages of osteogenic differentiation. OBJECTIVE:To explore alkaline phosphatase expression and autophagy periodontal ligament stem cells levels in periodontitis and normal conditions. METHODS:Periodontal ligament stem cells from normal and periodontitis patients were isolated and cultured,and underwent Vimentin,pan-CK,and Stro-1 fluorescence staining.At 3,7,and 14 days of osteogenic differentiation,western blot assay was used to detect the protein expression levels of alkaline phosphatase,LC3B,Beclin1,and ATG5 in normal and inflammatory periodontal ligament stem cells.The mRNA expression levels of alkaline phosphatase,bone sialoprotein,osteocalcin,Runx2,LC3B,Beclin1,and ATG5 were detected by real-time PCR. RESULTS AND CONCLUSION:(1)Stro-1 was positive,Vimentin was positive,and pan CK was negative in periodontal ligament stem cells.(2)At 3,7,and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the mineralization nodules formed by periodontal ligament stem cells from inflammatory sources were significantly reduced(P<0.01);the expression of alkaline phosphatase protein and mRNA was significantly lower(P<0.05);the mRNA expression levels of bone sialoprotein,osteocalcin,and Runx2 were significantly decreased(P<0.05).(3)At 7 and 14 days after osteogenic differentiation,compared with normal periodontal ligament stem cells,the expression levels of ATG5,LC3B,and Beclin1 proteins and mRNA of periodontal ligament stem cells were downregulated(P<0.05).These findings suggest that inflammation reduces the activity of periodontal ligament stem cells in mineralizing nodule formation and the expression of alkaline phosphatase and weakens the autophagy potential of periodontal ligament stem cells at 7 and 14 days after osteogenic differentiation.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.