SWI/SNF family mutations in advanced NSCLC: genetic characteristics and immune checkpoint inhibitors' therapeutic implication.

BACKGROUND: SWItch/Sucrose NonFermentable (SWI/SNF) mutations have garnered increasing attention because of their association with unfavorable prognosis. However, the genetic landscape of SWI/SNF family mutations in Chinese non-small-cell lung cancer (NSCLC) is poorly understood. In addition, the optimal treatment strategy has not yet been determined. PATIENTS AND METHODS: We collected sequencing data on 2027 lung tumor samples from multiple centers in China to comprehensively analyze the genomic characteristics of the SWI/SNF family within the Chinese NSCLC population. Meanwhile, 519 patients with NSCLC from Sun Yat-sen University Cancer Center were enrolled to investigate the potential implications of immunotherapy on patients with SWI/SNF mutations and to identify beneficial subpopulations. We also validated our findings in multiple publicly available cohorts. RESULTS: Approximately 15% of Chinese patients with lung cancer harbored mutations in the SWI/SNF chromatin remodeling complex, which were mutually exclusive to the EGFR mutations. Patients with SWI/SNFmut NSCLC who received first-line chemoimmunotherapy had better survival outcomes than those who received chemotherapy alone (median progression-free survival: 8.70 versus 6.93 months; P = 0.028). This finding was also confirmed by external validation using the POPLAR/OAK cohort. SWI/SNFmut NSCLC is frequently characterized by high tumor mutational burden and concurrent TP53 or STK11/KEAP mutations. Further analysis indicated that TP53 and STK11/KEAP1 mutations could be stratifying factors in facilitating personalized immunotherapy and guiding patient selection. CONCLUSIONS: This study provides a step forward in understanding the genetic and immunological characterization of SWI/SNF genetic alterations. Moreover, our study reveals substantial benefits of immunotherapy over chemotherapy for SWI/SNF-mutant patients, especially the SWI/SNFmut and TP53mut subgroups.

[Correlation between common driver gene variations and clinicopathological typing in lung adenocarcinoma].

Objective: To correlate the common driver gene variations in primary lung adenocarcinoma with their clinical characteristics and histopathological subtypes. Methods: There were 4 995 cases of primary lung adenocarcinoma diagnosed at Weifang People's Hospital of Shandong Province from January 2015 to December 2021 which were retrospectively analyzed. Among them 1 983 cases were evaluated for their histopathological subtype; 3 012 were analyzed for the correlation of their histopathological subtypes and corresponding driver gene variations, including invasive non-mucinous adenocarcinoma (INMA) and invasive mucinous adenocarcinoma (IMA), and morphologically, poorly-differentiated, moderately-differentiated and well-differentiated adenocarcinomas. Next-generation sequencing was used to detect variations in EGFR, KRAS, ALK, RET, ROS1, MET, HER2, or BRAF driver genes. Results: There were 2 384 males and 2 611 females. EGFR and ALK variations were more commonly found in female patients aged 60 years or older, with EGFR mutation rate in clinical stage Ⅰ (25.80%) significantly higher than in other stages (P<0.05). KRAS mutations were more commonly detected in male smokers aged 60 years or older, HER2 mutations were more commonly in patients younger than 60 years, and RET mutations were more commonly in non-smokers (all P<0.05). No correlation was found between ROS1, MET, and BRAF gene variations and their clinical characteristics (P>0.05). For the histopathological subtypes, among the 1 899 cases of acinar adenocarcinoma, EGFR mutation rate was the highest (67.30%) compared to the other genes. Exon 21 L858R and exon 19 del were the main mutation sites in IMA and INMA, with a higher mutation rate at exon 20 T790M (11.63%) in micropapillary adenocarcinoma. In IMA, KRAS had the highest overall mutation rate (43.80%), with statistically significant difference in mutation rates of exon 2 G12D and exon 2 G12V in acinar adenocarcinoma, solid, and IMA (P<0.05). KRAS mutation at various sites were higher in poorly differentiated groups compared to moderately- and well-differentiated groups (P<0.05). HER2 mutations were more commonly observed in acinar adenocarcinoma, papillary, and micropapillary adenocarcinoma of INMA. BRAF mutation was higher in micropapillary adenocarcinoma compared with other types (P<0.05). Conclusions: Variations in EGFR, ALK, KRAS, HER2, and RET in primary lung adenocarcinoma are associated with patients' age, smoking history, and clinical stage, and driver gene mutations vary among different histopathological subtypes. EGFR mutations are predominant in INMA, while KRAS mutations are predominant in IMA.

[Correlations between the average Young's modulus and histopathological characteristics of papillary thyroid carcinoma].

Objective: To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC). Methods: Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean. Results: The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean (r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean (r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without (P=0.014). There were statistical differences in the Emeans among different types of pathological calcification (P＜0.001). The multiple linear regression analysis showed that the lesion size (ß=0.325, P＜0.001), degree of fibrosis (ß=0.563, P＜0.001), psammoma bodies (ß=0.177, P=0.001), stromal calcification (ß=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma (ß=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions: The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

Correlation between angiotensin and acute kidney injury in patients with sepsis.

OBJECTIVE: The aim of the study was to analyze the changes in angiotensin (Ang) levels in patients with sepsis complicated with acute kidney injury (AKI) and evaluate the relationship between Ang and AKI. PATIENTS AND METHODS: Prospective research methods were used in this study. A total of 66 sepsis patients admitted to the Intensive care Unit (ICU) of the First Hospital of Hebei Medical University from October 2020 to January 2021 were enrolled. According to the occurrence of AKI, patients were divided into the sepsis-associated AKI (SA-AKI) group and the non-AKI group. The levels of Ang-1 and Ang-2 were compared between the two groups. The relationship between Ang and glomerular filtration rate (GFR) in sepsis patients was studied by correlation analysis. RESULTS: Plasma Ang-1 in the SA-AKI group was significantly higher than that in the non-AKI group (0.39±1.05 ng/ml vs. 0.10±0.24 ng/ml, p=0.039). The Ang-2/Ang-1 in the SA-AKI group was lower than that in the non-AKI group with a significant difference (52.55±191.38 vs. 349.50±327.49, p=0.001). Correlation analysis indicated that Ang-1 was negatively correlated with GFR (r=-0.12, p=0.031), while Ang-2/Ang-1 was positively correlated with GFR (r=0.21, p<0.001). The Ang-2 was positively correlated with GFR (r=0.204, p<0.001) CONCLUSIONS: Plasma Ang-1 and Ang-2 levels are suggestive for assessing the risk of AKI in patients with sepsis.

[The harvestion and application experience of free multi-lobed anterior thigh flap].

Objective: To introduce the technique and clinical application of free lobed anteromedial thigh perforator pedicle flap. Methods: From September 2015 to September 2021, 72 patients with perforating buccal and oral cancer defects were treated at the Oncology Plastic Surgery Department of Hunan Cancer Hospital. There were 61 males and 11 females, with an average age of 36.7 years (31-56 years). According to Union for International Cancer Control (UICC) TNM staging, there were 20 cases of T3N1M0, 13 cases of T3N2M0, 24 cases of T4N0M0, and 15 cases of T4N1M0. All defects were planned to be repaired with free lobed anteromedial perforator flaps. When there was only one set of vascular pedicle, the perforating vascular pedicle artery was anastomosed with the superior thyroid artery, and the accompanying vein was anastomosed with the superior thyroid vein by end-to-end. Results: The areas of soft tissue defects after radical resection of oral and buccal cancers in 72 patients were between 5.0 cm × 4.0 cm and 11.0 cm×7.0 cm; the areas of the first anterior femoral skin islands were between 5.0 cm × 4.0 cm and 13.0 cm×7.0 cm; the areas of the second anterior femoral skin islands were between 5.0 cm × 3.0 cm and 10.0 cm × 7.0 cm; and all flap donor sites were directly closed. In 35 cases, the vascular pedicle was accompanied by a lateral femoral muscle flap for filling the gap defect at the base of the mouth. The average length of the vascular pedicles of the flaps was 7.2 cm (range: 6.8-8.2 cm). The average diameter of the vascular pedicle arteries was 1.6 mm (range: 1.4-2.2 mm). The blood flow reconstruction of flap was completed by anastomosing one accompanying vein. The average diameter of the accompanying veins was 2.1 mm (range: 1.6-2.8 mm). Postoperative hematoma occurred in 3 patients, with one having vascular crisis. After emergency exploration, 2 of them were successfully saved, and the other one had complete necrosis of skin flap, which was repaired by pedicled pectoralis major skin flap transplantation. With following up of 12-38 months, the appearances of the flaps were satisfactory without significant swelling. The mouth opening and language function were satisfactory in all cases, and only linear scars were left in the donor sites, with no significant impact on thigh functions. Five patients with local recurrence of tumor were treated with second radical resection and repair with pedicled pectoralis major myocutaneous flap. Six patients developed cervical lymph node metastasis (4 on the same side and 2 on the opposite side) and underwent neck dissection again. Conclusion: The anatomical basis of the branches of the anteromedial femoral perforating branches in the anterolateral region of the thigh can be helpful to prepare the anterolateral femoral lobed flap, which is suitable for repairing the perforating defects after the radical operation of oral and buccal cancers.

[Burden of non-communicable diseases attributable to population aging in China, 1990‒2050].

Objective: The direction and intensity of population aging on the burden of non-communicable diseases (NCDs) in China from 1990 to 2019 were analyzed, and the burden of NCDs in 2050 was predicted. Methods: The disease-specific disability-adjusted life years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) in the Chinese population from 1990 to 2019 were obtained from the Global Burden of Disease Study.The differences in indicators from 1990 to 2019 were attributed to the contribution of age structure, population size, and all other causes. The Bayesian age-time-cohort models were used to predict DALYs from NCDs to 2050. Results: The absolute level of DALYs caused by NCDs increased by 7.460 million from 1990 to 2019, and the age structure contributed 186.0% (95% Uncertainty Intervals (UIs): 178.4%-193.6%), population size contributed 77.0% (95% UIs: 69.5%-80.8%), all other causes contributed -163.0% (95% UIs:-163.1%- -159.3%). DALYs caused by NCDs consist of 2.527 million YLLs and 4.934 million YLDs, in which the contribution of age structure to YLLs and YLDs was 414.6% (95% UIs: 396.2%-432.5%) and 69.1% (95% UIs: 66.7%-71.4%), respectively. From 2019 to 2050, the diseases with increased DALYs due to changes in age structure are cardiovascular diseases, neoplasms, chronic respiratory diseases, neurological disorders, sense organ diseases, diabetes and kidney diseases, musculoskeletal disorders, digestive diseases, mental disorders, and skin and subcutaneous diseases in descending order. Conclusions: From 1990 to 2019, except for skin and subcutaneous diseases, the burden of other NCDs attributable to population aging increased, mainly due to disability. By 2050, the burden of NCDsattributable to population aging will continue to rise.

[Effects of long working hours exposure on occupational stress and depression symptoms in couriers in Zhejiang Province].

Objective: To understand the current situation of long working hours exposure of couriers in Zhejiang Province, and to analyze the influence of long working hours exposure levels on their occupational stress and depression symptoms, and provide a basis for promoting the physical and mental health of couriers. Methods: From September to December 2021 , 1159 couriers from Zhejiang Express Transport Companies were selected as respondents by cluster sampling, and their basic information were collected. The occupational stress and depression symptoms of the couriers were assessed using the Core Occupational Stress Scale (COSS) and the Patient Health Questionnaire-9 (PHQ-9). The effects of long work hours (>48 h per week) on the occupational stress and depression symptoms of the couriers were analyzed. Results: The average age of 1159 courier in Zhejiang Province was (33.24±8.42) years, the average weekly working hours were (63.21±18.77) h, and 75.15% (871/1159) were long-term workers. The detection rates of occupational stress and depression symptoms in courier were 32.44% (376/1159) and 32.53% (377/1159), respectively. There were significant differences in the detection rates of occupational stress and depression symptoms among couriers with different ages, educational background, marital status, monthly average income, length of service, position or post, shift status, drinking status, and average weekly working hours (P <0.05). The adjusted logistic regression analysis showed that, after adjusting for the influence of confounding factors such as age, educational background, marital status, monthly average income, length of service, position or post, shift status and drinking status, compared with the weekly working hours ≤48 h, weekly working hours of 63-77 h, 78-92 h, ≥93 h were the risk factors for occupational stress (OR=1.547, 95%CI: 1.019-2.350; OR=1.886, 95%CI: 1.184-3.006; OR=2.338, 95%CI: 1.188-4.062) and depression symptoms (OR=1.897, 95%CI: 1.258-2.860; OR=2.041, 95%CI: 1.290-3.230; OR=4.978, 95%CI: 2.551-9.715) of couriers (P<0.05) . Conclusion: Long working hours could increase the risk of occupational stress and depression symptoms among couriers. It is necessary to arrange working hours reasonably to reduce the occurrence of occupational stress and depression symptoms of couriers.

[Analysis of different protein expression levels in peripheral blood circulating tumor cells from patients with diffuse large B-cell lymphoma and their predictive efficiency for recurrence].

Objective: To analyze the expression levels of differentiation cluster 47 (CD47), signal regulatory protein α (SIRP-α), proto-oncogene (MYC) and proliferating cell associated antigen (Ki67) proteins in peripheral blood circulating tumor cells (CTC) from patients with diffuse large B-cell lymphoma and their predictive efficiency for tumor recurrence. Methods: The data of 82 patients with diffuse large B-cell lymphoma who were confirmed by histopathology and were in remission after chemotherapy in the Hematology Department of Linyi People's Hospital from January 2018 to January 2021 were retrospectively analyzed. There were 44 males and 38 females, and aged from 50 to 75 (63.8±4.6) years. The patients were divided into recurrent group (n=36) and non-recurrent group (n=46) according to their recurrence within 1 year after remission. The fasting peripheral venous blood samples (4 ml) from patients in the morning were collected, and the CTC were isolated. The expression levels of CD47, SIRP-α, MYC and Ki67 proteins in CTC were detected by Western blotting. The correlations between CD47 expression level and SIRP-α, MYC and Ki67 expression levels were analyzed by Pearson correlation analysis. The predictive efficiency of CD47, SIRP-α, MYC and Ki67 expression levels on tumor recurrence was evaluated by receiver operating characteristic (ROC) curves, and the areas under the curve (AUC) were calculated. Results: The expression levels of CD47, SIRP-α, MYC and Ki67 in recurrent group were 2.24±0.23, 1.17±0.12, 1.98±0.20 and 2.63±0.27, while those in non-recurrent group were 2.04±0.21, 1.31±0.13, 1.53±0.16 and 2.24±0.25. The expression levels of CD47, MYC and Ki67 in the recurrent group were higher than those in the non-recurrent group, while the expression levels of SIRP-α were lower than those in the non-recurrent group (all P<0.001). In 82 patients, the expression levels of CD47, SIRP-α, MYC and Ki67 were 2.13±0.22, 1.25±0.13, 1.73±0.18 and 2.41±0.26, respectively. The expression level of CD47 was negatively correlated with the expression level of SIRP-α (r=-0.308, P=0.005), but positively correlated with the expression level of MYC and Ki67 (r=0.484 and 0.332, P=0.012 and 0.003). The sensitivity of CD47, SIRP-α, MYC and Ki67 expression levels in predicting recurrence of diffuse large B-cell lymphoma was 66.7%, 72.2%, 72.2% and 66.7%, with the specificity of 67.4%, 71.7%, 67.4% and 71.7%, and AUC (95%CI) of 0.694 (0.582-0.791), 0.693 (0582-0.790), 0.714 (0.603-0.808) and 0.709 (0.598-0.804), respectively. The sensitivity of the combined detection of the above four indicators was 83.3%, with the specificity of 78.3% and the AUC (95%CI) of 0.864 (0.771-0.930), which was higher than those of the individual detection of each indicator (all P<0.05). Conclusions: The expression level of CD47 was negatively correlated with the expression level of SIRP-α, but positively correlated with the expression level of MYC and Ki67. The expression levels of CD47, SIRP-α, MYC and Ki67 have certain predictive value for tumor recurrence in patients with diffuse large B-cell lymphoma, and the predictive efficiency of combined detection is higher than single indicator detection.

[Attach great importance to the significance of serum anti-müllerian hormone and androgen in the evaluation of polycystic ovary syndrome].

Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of childbearing age, which seriously affects women's reproductive health. In recent years, more and more studies have found that serum anti-Müllerian hormone (AMH) has certain significance in the diagnosis and treatment evaluation of PCOS. In addition, with the improvement of detection methods, more attention has been paid to the significance of female androgens and AMH in the evaluation of PCOS. This article reviews the recent research progress of serum AMH and androgens in the evaluation of PCOS.

Mesenchymal stem cells transplantation for perianal fistulas: a systematic review and meta-analysis of clinical trials.

BACKGROUND: Perianal fistulas, characterised as granulomatous inflammation of fistulas around the anal canal, are associated with significant morbidity resulting in a negative impact on quality of life and a tremendous burden to the healthcare system. Treatment of anal fistulas usually consists of anal surgery; however, results of closure rates are not satisfactory especially with complex perianal fistulas, after which many patients may suffer from anal incontinence. Recently, the administration of mesenchymal stem cells (MSCs) has shown promising efficacy. Herein, we aim to explore whether MSCs are effective for complex perianal fistulas and if they have either short-term, medium-term, long-term or over-long-term efficacy. Additionally, we want to elucidate whether factors such as drug dosage, MSC source, cell type, and disease aetiology influence treatment efficacy. We searched four online databases and analysed data based on information within the clinical trials registry. The outcomes of eligible trials were analysed with Review Manager 5.4.1. Relative risk and related 95% confidence interval were calculated to compare the effect between the MSCs and control groups. In addition, the Cochrane risk of bias tool was applied to evaluate the bias risk of eligible studies. Meta-analyses showed that therapy with MSCs was superior to conventional treatment for complex perianal fistulas in short-, long- and over-long-term follow-up phases. However, there was no statistical difference in treatment efficacy in the medium term between the two methods. Subgroup meta-analyses showed factors including cell type, cell source and cell dosage were superior compared to the control, but there was no significant difference between different experimental groups of those factors. Besides, local MSCs therapy has shown more promising results for fistulas as a result of Crohn's Disease (CD). Although we tend to maintain that MSCs therapy is effective for cryptoglandular fistulas equally, more studies are needed to confirm this conclusion in the future. SHORT CONCLUSION: MSCs Transplantation could be a new therapeutic method for complex perianal fistulas of both cryptoglandular and CD origin showing high efficacy in the short-term to over-long-term phases, as well as high efficacy in sustained healing. The difference in cell types, cell sources and cell dosages did not influence MSCs' efficacy.

[Clinical analysis of 11 cases of pregnancy with aortic dissection].

Objective: To investigate the treatment and maternal and fetal outcomes of pregnant women with aortic dissection (AD). Methods: The clinical data of 11 pregnant women with AD treated at the First Affiliated Hospital of Air Force Military Medical University from January 1st, 2011 to August 1st, 2022 were collected, and their clinical characteristics, treatment plans and maternal and fetal outcomes were analyzed retrospectively. Results: (1) Clinical characteristics: the age of onset of 11 pregnant women with AD was (30±5) years old, and the week of pregnancy of onset was (31.4±8.0) weeks. Clinical manifestations: the main symptoms were sudden onset of chest and back pain or low back pain. Type of AD: 8 cases of Stanford type A, and 3 cases of type B. The aortic width was (42±11) mm. Diagnostic methods: the diagnosis of AD was confirmed by transthoracic echocardiography (TTE), computed tomography angiography (CTA) or enhanced CT examination, among which 4 cases were confirmed by CTA examination, 4 cases by TTE examination, and 3 cases by enhanced CT examination. Laboratory results: white blood cell count was (15.4±8.7) ×109/L, neutrophil count was (13.5±8.5) ×109/L, the median D-dimer level was 2.7 mg/L (2.1-9.2 mg/L), and the median fibrin degradation products level was 12.0 mg/L (5.4-36.1 mg/L). (2) Treatments: all 11 patients were admitted to hospital in emergency. Before operation, the departments of cardiac surgery, obstetrics, pediatrics and anesthesiology cooperated to develop individualized treatment plan. Aortic surgery was performed in 11 pregnant women with AD. In 6 of them, pregnancy termination was performed at the same time as aortic surgery, and aortic surgery was performed after cesarean section. Four cases of pregnancy termination and aortic operation were performed by stages, including aortic operation after cesarean section in 2 cases, and cesarean section after aortic operation in 2 cases. One case (12+6 weeks of gestation) had spontaneous abortion on the day after aortic surgery. The gestational age of the 11 patients on pregnancy termination was (32.9±7.4) weeks. Aorta surgical methods: 7 patients received under extracorporeal circulation ascending aorta replacement ± aortic valve replacement ± coronary artery transplantation (or coronary artery bypass transplantation)± left and right coronary Cabrol + total arch replacement (or aortic arch replacement)± stent implantation, 1 patient received under extracorporeal circulation aortic root replacement, and 3 patients underwent aortic endoluminal isolation. (3) Maternal and fetal outcomes: among the 11 pregnant women with AD, 9 (9/11) survived, 2 (2/11) died with lower limb ischemia before the onset of the disease. A total of 10 newborns were born in 9 pregnant women after delivery (1 of them was twins), and the 2 cases were spontaneous abortion after aortic surgery in the first trimester (12+6 weeks) and fetal death after hysterotomy in the second trimester (26+3 weeks), respectively. Among the 10 surviving neonates, 3 were full-term infants and 7 were premature infants. The birth weight of newborn was (2 651±784) g. Respiratory distress syndrome was found in 6 cases. The newborns were followed up for (5.6±3.6) years after birth, and the infants developed well during the follow-up period. Conclusions: Pregnancy complicated with AD is dangerous, and chest and back pain is the main clinical manifestation of this disease. With early identification and selection of appropriate diagnostic methods, multidisciplinary diagnosis and treatment, mother and children could obtain good outcomes.

[Clinical characteristics of central nervous system involvement in IgG4 related diseases].

OBJECTIVE: To improve the understanding of the clinical characteristics of immunoglobulin G4-related disease (IgG4-RD) with central nervous system (CNS) involvement, so as to contribute to the early diagnosis and treatment. METHODS: In this study, 10 patients with IgG4-RD with CNS involvement were selected. Clinical data including demographic features, clinical manifestations, organ involvement, laboratory findings, radiological results, pathology, treatments and outcomes were collected retrospectively. RESULTS: Among the 10 IgG4-RD patients complicated with CNS involvement, 6 cases manifested as pituitary involvement and 4 cases manifested as dural involvement. Only 2 patients had nervous system involvement alone, while the left patients were complicated with other organ involvement besides nervous system. Half of the patients presented nervous system involvement as the initial manifestation, and the main symptoms of nervous system included polydipsia, polyuria, headache, decreased vision and so on. In the laboratory examination, the serum IgG4 level was increased in 9 cases (90.0%), and the total serum IgE was increased in 7 cases (87.5%). At the same time, their IgG, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were increased, while complement (C) 3 and C4 were decreased in some patients. Eight patients underwent tissue biopsies in different parts, the pathological examination showed a large number of lymphocyte and plasma cell infiltration, accompanied by fibrous tissue proliferation in part. All the patients were treated with glucocorticoids, and 8 cases (80%) were given immunosuppressants at the same time, and 3 cases were treated with rituximab when they expe-rienced disease relapse. As a result, 2 cases (20%) achieved complete remission (CR), and 8 cases (80%) achieved partial remission (PR). The median follow-up time was 13.5 months, and 4 cases relapsed. CONCLUSION: Pituitary and dura are common affected organs of IgG4-RD with CNS involvement. Most IgG4-RD patients with CNS involvement are combined with other organ involvement, but half of them presented nervous system involvement as the initial manifestation, and the symptoms are not typical. In order to make an early diagnosis, laboratory, imaging examination and tissue biopsy should be taken into consideration in combination if necessary.

[Clinical effects of transplantation of turbocharged bipedicle deep inferior epigastric perforator flap in breast reconstruction].

Objective: To explore the clinical effects of transplantation of turbocharged bipedicle deep inferior epigastric perforator (DIEP) flap in breast reconstruction. Methods: A retrospective observational study was used. From December 2008 to December 2016, 24 patients who met the inclusion criteria were treated in the Department of Plastic Surgery of Hunan Cancer Hospital, all patients were female, aged 28-51 (36.5±1.6) years. All cases received turbocharged bipedicle DIEP flap for two-staged breast reconstruction. According to the patterns of turbocharged vessels anastomosis, the turbocharged bipedicle DIEP flaps with length of (27.5±0.3) cm and width of (12.8±1.4) cm, were divided into three types: distal end of pedicle anastomosis type, main branch of pedicle anastomosis type, and muscular branch of pedicle anastomosis type. After complete hemostasis in the donor region, the anterior sheath was repaired with intermittent suture, and umbilical reconstruction was completed. Two negative pressure drainage tubes were indwelled, and subcutaneous tissue and skin were sutured layer by layer. The specific ways of vascular anastomosis of the flap pedicle with the internal thoracic vessels of recipient site included anastomosing the proximal end of one artery and one vein, anastomosing the proximal and distal end of one artery and one vein, and anastomosing the proximal end of one artery and two veins. Postoperatively, the survival and blood supply of flaps were observed. The patients were followed up to observe the reconstructed breast shape satisfaction, donor site complications, abdominal wall function, and scar hyperplasia. Results: All turbocharged bipedicle DIEP flaps for two-staged breast reconstruction survived well, with good blood supply. During follow-up for 14 to 56 (20±6) months, the shape of reconstructed breasts was satisfied. Only linear scar was left in the donor sites of abdomen with no complications, and the function of abdominal wall was not affected. Conclusions: For patients with clear indications, transplantation of free turbocharged bipedicle DIEP flap is a safe, reliable, and satisfactory choice for breast reconstruction with autologous tissue.

[The risk prediction models for occurrence of cervical cancer: a systematic review].

Objective: To systematically summarize and assess risk prediction models for occurrence of cervical cancer and to provide evidence for selecting the most reliable model for practice, and guide cervical cancer screening. Methods: Two groups of keywords related to cervical cancer and risk prediction model were searched on Chinese databases (CNKI, and Wanfang) and English databases (PubMed, Embase, and Cochrane Library). Original articles that developed or validated risk prediction models and published before November 21, 2019, were selected. Information form was created based on the CHARMS checklist. The PROBAST was used to assess the risk of bias. Results: 12 eligible articles were identified, describing 15 prediction models, of which five were established in China. The predicted outcomes included multiple stages from cervical precancerous lesions to cancer occurrence, i.e., abnormal Pap smear (1), occurrence or recurrence of CIN (9), and occurrence of cervical cancer (5), etc. The most frequently used predictors were HPV infection (12), age (7), smoking (5), and education (5). There were two models using machine learning to develop models. In terms of model performance, the discrimination ranged from 0.53 to 0.87, while only two models assessed the calibration correctly. Only two models were externally validated in Taiwan of China, using people in different periods. All of the models were at high risk of bias, especially in the analysis domain. The problems were concentrated in the improper handling of missing data (13), preliminary evaluation of model performance (13), improper use of internal validation (12), and insufficient sample size (11). In addition, the problems of inconsistency measurements of predictors and outcomes (8) and the flawed report of the use of blindness for outcome measures (8) were also severe. Compared with the other models, the Rothberg (2018) model had relatively high quality. Conclusions: There are a certain number of cervical cancer risk prediction models, but the quality is poor. It is urgent to improve the measurement of predictors and outcomes, the statistical analysis details such as handling missing data and evaluation of model performance and externally validate existing models to better guide screening.

[Comparison of clinical characteristics between sporadic gastrinoma and multiple endocrine neoplasia type 1-related gastrinoma].

Objective: To compare clinical characteristics of sporadic gastrinoma and multiple endocrine neoplasia type 1 (MEN1)-related gastrinoma. Methods: A retrospective cohort study was conducted. Patients with clinical manifestations of Zollinger-Ellison syndrome, pathological diagnosis as neuroendocrine neoplasm (NEN) and complete clinical and follow-up data were enrolled. Patients with only high gastric acid secretion but without evidence of NEN, or with other concurrent non-NEN tumors were excluded. According to the above criteria, the clinicopathological data of 52 cases of gastrinoma diagnosed from April 2003 to December 2020 in the First Affiliated Hospital, Sun Yat-sen University, were collected. Patients who met the diagnostic criteria of gastrinoma and met one of the following conditions were diagnosed as MEN1-related gastrinoma: (1) the presence of pathogenic mutations in the MEN1 gene confirmed by genetic testing; (2) NENs involving two or more endocrine glands, namely, pituitary, parathyroid, thymic, pancreatic, and adrenal NENs; (3) NEN and at least one first-degree relatives diagnosed as MEN1. The remaining gastrinomas were defined as sporadic gastrinoma. Student's t test and chi-square test were used for statistical analysis. Clinicopathological characteristics, endoscopic findings, imaging characteristics, treatment, and prognosis of sporadic and MEN1-related gastrinoma were compared. Results: Among 52 patients with gastrinoma, 33 were sporadic gastrinoma and 19 were MEN1-related gastrinoma. The common symptoms of both sporadic and MEN1-related gastrinomas were diarrhea (24/33, 72.7%; 17/19, 89.5%) and abdominal pain (19/33, 57.6%; 9/19, 47.4%). Compared with sporadic gastrinoma, MEN1-related gastrinoma needed longer time for diagnosis [(7.4±4.9) years vs. (3.9±5.2) years, t=-2.355, P=0.022), were more likely multiple tumors [47.4% (9/19) vs. 15.2% (5/33), χ(2)=6.361, P=0.012], had smaller diameter [(1.7±1.0) cm vs. (3.1±1.8) cm, t=2.942, P=0.005), presented the lower tumor grade [G1: 83.3% (15/18) vs. 39.4% (13/33); G2: 11.1% (2/18) vs. 54.5% (18/33); G3: 5.6% (1/18) vs. 6.1% (2/33), Z=-2.766, P=0.006], were less likely to have serum gastrin which was 10 times higher than normal [11.8% (2/17) vs. 56.0% (14/33), χ(2)=8.396, P=0.004], had higher probability of complication with type 2 gastric neuroendocrine tumors (g-NET) [31.6% (6/19) vs. 3.0%(1/33), χ(2)=6.163, P=0.013], and had lower rate of liver metastasis [21.1% (4/19) vs. 51.5% (17/33), χ(2)=4.648, P=0.031). There was no obvious difference between sporadic gastrinomas and MEN1-related gastrinomas in endoscopic findings. Both types presented enlarged and swollen gastric mucosa under the stimulation of high gastric acid, and multiple ulcers in the stomach and duodenum could be seen. Gastrinoma with type 2 g-NET presented multiple polypoid raised lesions in the fundus and body of the stomach. (68)Ga-SSR-PET/CT scan had a 100% detection rate for both types while (18)F-FDG-PET/CT scan had a higher detection rate for sporadic gastrinoma compared with MEN1-related gastrinoma [57.9% (11/19) vs. 20.0% (3/15), χ(2)=4.970, P=0.026]. Among the patients with sporadic gastrinoma, 19 received surgical treatment, 1 underwent endoscopic submucosal dissection, 8 underwent transcatheter arterial embolization (TAE), and 5 underwent surgery combined with TAE. Among patients with MEN1-related gastrinoma, 13 received surgical treatment, and the other 6 received conservative treatment. The median follow-up of all the patients was 21.5 (1-129) months, and the 5-year survival rate was 88.4%. The 5-year survival rate of patients with sporadic and MEN1-related gastrinomas was 89.5% and 80.0% respectively (P=0.949). The 5-year survival rate of patients with and without liver metastasis was 76.2% vs. 100%, respectively (P=0.061). Conclusions: Compared with sporadic gastrinoma, MEN1-related gastrinoma has longer diagnosis delay, smaller tumor diameter, lower tumor grading, lower risk of liver metastasis, and is more likely to complicate with type 2 g-NET, while there is no difference in survival between the two tumor types.

[Clinical characteristics and related factors of human respiratory syncytial viruses infection in premature infants within 2 years after birth in Shenzhen Children's Hospital].

Objective: To analyze the clinical characteristics and factors associated with human respiratory syncytial virus (HRSV) infection in preterm infants within the first 2 years of life. Methods: Children with respiratory tract infections admitted to Shenzhen Children's Hospital during the 3-year period from January 2016 to December 2018 who were <2 years old and whose gestational age at birth was <37 weeks were selected, and those who met the diagnostic criteria for RSV infection were categorized as the positive case group, and those who had no detectable influenza virus, parainfluenza virus and adenovirus antigens were categorized as the negative group. The clinical characteristics of the case group were retrospectively analyzed. A multivariable logistic regression model was used to analyze the associated factors. Results: A total of 1, 483 children were included, of whom 149 (10.1%) were HRSV positive (case group) and 447 (30.1%) were in the negative group (control group). In the case group, there were 88 (59.1%) male and 61 (40.1%) female children; 127 children (85.2%) in the mild-to-moderate disease group and 22 children (14.8%) in the severe disease group. The number of cases in the severe disease group was greater than that in the mild-to-moderate disease group [(17 cases, 77.3%) than (59 cases, 46.5%)], with statistical significance (P=0.010). A total of 117 cases (78.5%) had onset from February to July. Multivariable analysis showed that males [OR (95%CI) of 0.105 (0.013-0.112)], age at month [0.045 (0.036-0.112)], congenital heart disease [0.388 (0.206-0.940)] and bronchopulmonary dysplasia [0.622 (0.484-0.927)] were positively associated with HRSV infection in preterm infants. Conclusion: The high prevalence of HRSV infection in preterm infants in Shenzhen is from February to July each year, and male children are more common. Young age, congenital heart disease and bronchopulmonary dysplasia are all independent risk factors for HRSV infection in preterm infants.

microRNA-29b mediates Th17/Treg imbalance in chronic obstructive pulmonary disease by targeting IL-22.

Chronic obstructive pulmonary disease (COPD) represents a chronic inflammatory disorder of the airways induced mainly by cigarette smoking. In the current study, cigarette smoke extract (CSE) was used to develop an in vitro COPD model using human bronchial epithelium (HBE) cells to expound the possible role of microRNA-29b (miR-29b) in COPD. Firstly, miR-29b and interleukin (IL)-22 expression was assessed in serum of 20 healthy non-smokers, 20 healthy smokers and 20 COPD patients as well as CSE-treated HBE cells. Then, miR-29b and IL-22 expression was altered to evaluate their functions in Th17/Treg ratio. miR-29b inhibited Th17/Treg ratio and levels of IL-22; whereas overexpression of IL-22 reversed these trends. Moreover, rescue experiments found that IL-22 neutralized the repressive effects of miR-29b on Th17/Treg ratio and inflammatory response. Finally, we found that miR-29b blocked the JAK/STAT3 pathway in CSE-treated HBE cells. These data highlighted that miR-29bs modulated Th17/Treg imbalance in CSE-induced experimental COPD through inhibition of IL-22-dependent JAK/STAT3 pathway.