[Analysis of the safety, accuracy, and factors influencing bleeding complications in CT-guided puncture biopsy of brain occupying lesions].

Objective: To investigate the safety and accuracy of CT-guided intracranial puncture biopsy and the possible influencing factors of postoperative bleeding complications. Methods: A case series study. A retrospective analysis was conducted on 101 patients who underwent CT-guided intracranial puncture biopsy at the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2021. The basic data of patients and the safety and accuracy of CT-guided intracranial puncture biopsy were analyzed statistically. Univariate and multivariate logistic regression analysis were used to screen the influencing factors of bleeding complications in CT-guided intracranial puncture biopsy, and the bleeding complications in glioma subgroup were analyzed. Results: Among the 101 patients, 53 were males and 48 were females, aged (53.7±17.2) years. The average diameter of intracranial lesions was (3.5±1.4) cm, while the vertical distance from the lesion to the meninges was (2.4±1.7) cm. The needle's intracranial depth reached (3.2±1.8) cm, with adjustments averaging (3±1) occurrences and an average procedural duration of (40.2±12.9) minutes. Pathological diagnoses included glioma (36 cases), gliosis (3 cases), lymphoma (32 cases), metastatic tumors (7 cases), inflammatory lesions (13 cases), and 10 indeterminate cases. The positive rate of puncture pathology was 90.1% (91/101), and the diagnostic coincidence rate was 94.0% (78/83). The incidence of bleeding complications in CT-guided intracranial puncture biopsy was 26.7% (27/101), of which 23 cases had small intratoma or needle path bleeding, 4 cases had massive bleeding, and 2 cases died. The patients were divided into bleeding group (n=27) and no bleeding group (n=74), according to the presence or absence of bleeding. The results of univariate logistic regression analysis showed that thrombin time≥15 s and the number of needle adjustment were the factors affecting the occurrence of bleeding complications (both P<0.05), and the results of multivariate logistic regression showed that thrombin time≥15 s was the related factor for bleeding. Patients with thrombin time≥15 s had a 3.045 times higher risk of bleeding than those with thrombin time<15 s (OR=3.045,95%CI:1.189-7.799,P=0.020). Among the 101 patients, 36 cases of midbrain glioma were divided into low-grade glioma group (n=11) and high-grade glioma group (n=25) according to the pathological grade. Subgroup analysis showed that the risk of bleeding for high-grade gliomas was 9.231 times higher than that for low-grade gliomas (OR=9.231,95%CI:1.023-83.331,P=0.031). Conclusions: CT-guided intracranial puncture biopsy is safe and feasible with high accuracy. Complication rates are associated with thrombin time≥15 s, especially high-grade glioma, which increases the risk of postoperative bleeding.

Construction of molecular subgroups of ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS: Patients with UC were classified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-α antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC.

[Efficacy of off-pump minimally invasive via a single left intercostal space incision compared with median sternotomy multi-vesselcoronary artery bypass grafting].

Objective: To compare the efficacy of off-pump minimally invasive cardiac surgery (MICS) via a single left intercostal space incision with median sternotomy multi-vesselcoronary artery bypass grafting (CABG). Methods: Patients who were diagnosed with multi-artery coronary artery disease (CAD) in the Ward 10 of the Department of Cardiac Surgery, Beijing Anzhen Hospital Affiliated to Capital Medical University and underwent CABG from July 2019 to January 2022 were retrospectively collected. All the patients were divided into MICS group and conventional CABG group according to the surgical methods. The perioperative outcomes were compared between thetwo groups, including intraoperative blood loss, postoperative 24 h thoracic drainage volume, ventilation duration, length of stay (LOS) in intensive care unit (ICU) and total LOS in hospital. Intraoperative blood flow of graft vesselswas measured by transit-time flow measurement (TTFM) after vascular anastomosis, and mean flow (MF) and pulsatile index (PI) were compared between the two groups. Results: A total of 444 patients were in the final analysis, with 351 males and 93 females, and the mean age of (62.0±8.9) years. There were 179 patients in MICS group and 265 cases in conventional CABG group, respectively. There were no statistically significant differences in the preoperative profiles between the two groups (all P>0.05) except that younger age [(60.7±9.3) years vs (62.8±8.5) years, P=0.017] and lower proportion of female [10.1% (18/179) vs 28.3% (75/265), P<0.001] were detected in MICS group. Likewise, there was no significant difference in the number of graft vessels between MICS group (3.18±0.74) and conventional CABG group (3.28±0.86) (P=0.234). Compared with those in conventional CABG group, patients in MICS group showed longer operation duration [ (5.10±1.09) h vs (4.33±0.86) h], fewer intraoperative blood loss [500 (200, 700) ml vs 700 (600, 900) ml], fewer postoperative 24 h thoracic drainage volume [300 (200, 400) ml vs 400 (250, 500) ml], shorter postoperative ventilation duration [15.0 (12.0, 17.0) h vs 16.5 (12.5, 19.0) h, P<0.001], LOS in ICU [18.0 (15.0, 20.0) h vs 20.0 (16.0, 23.0) h, P<0.001] and total LOS in hospital [(12.6±2.7) d vs (14.5±3.9) d, P<0.001]. MI and PI of graft vessels were similar between the two groups (both P>0.05). Moreover, there were no significant differences in major perioperative complications (i.e., repeat thoracotomy, incision infection, stroke) and mortality between the two groups (all P>0.05). Conclusion: MICS is an alternative treatment for patients with multi-vessel CAD with better perioperative outcomes compared with conventional CABG.

[Gray zone lymphoma: five cases report and literature review].

Objective: To investigate the clinical and pathological features, treatment, and prognosis of gray zone lymphoma (GZL) . Methods: From July 2, 2013, to February 10, 2021, the clinical and pathological features, treatment, and outcomes of five patients with GZL at the Blood Diseases Hospital, Chinese Academy of Medical Sciences were studied retrospectively. Results: There were one male and 4 females, with a median age of 28 (16-51) years at diagnosis. Four patients had mediastinal (thymic) involvement, two of which had superior vena cava obstruction syndrome, and 3 patients had extra-nodal involvement. There was one case with a limited Ann Arbor stage and 4 cases with a progressive stage. Three patients had cHL-like pathomorphology with scattered Hodgkin-like cells, strongly positive for CD20, positive for CD30, and CD15 was negative; the other two patients had both cHL and DLBCL morphology, with some areas resembling Hodgkin cells and some areas resembling immunoblasts, strongly positive for CD30, and CD15 but negative CD20. Two patients were treated with cHL-like regimens for induction and achieved only partial remission; after salvage therapy with enhanced DLBCL-like regimens, all achieved complete remission (CR) . Three patients were treated with enhanced DLBCL-like immunochemotherapy regimens for induction, and two patients were effective, one of whom achieved CR. Four patients who did not achieve CR were given second or third-line salvage therapy, and all of them recovered. One patient lost parity, one died of disease progression at 35.9 months after diagnosis, and the remaining three maintained sustained remission. Conclusions: GZL is uncommon, usually affects younger patients, is mediastinal and is diagnosed using path morphology and immunophenotype. Patients with newly diagnosed GZL appear to be more sensitive to DLBCL-like immunochemotherapy regimens; relapsed or refractory patients were tended with non-cross-resistant combination chemotherapy or with new drugs.

Endometrioid adenocarcinoma: combined multiparametric MRI and tumour marker HE4 to evaluate tumour grade and lymphovascular space invasion.

AIM: To assess the value of semi-quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and quantitative diffusion-weighted imaging parameters combined with human epididymis protein 4 (HE4) in predicting the pathological grade and lymphovascular space invasion (LVSI) of endometrioid adenocarcinoma (EAC). MATERIALS AND METHODS: Between October 2018 and December 2021, 60 women (mean age, 55 [range, 32-77] years) with EAC underwent preoperative pelvic MRI and HE4 level measurements. The positive enhancement integral (PEI), time to peak, maximum slope of increase (MSI), and maximum slope of decrease were measured by manually drawing a region of interest on the neoplastic tissue. The receiver operating characteristic curve was used to calculate the diagnostic efficiency of the single parameter and combined factors. RESULTS: Lower apparent diffusion coefficients (ADCs) were observed in high-grade tumours (G3) than in low-grade tumours (G1/G2). PEI, MSI, and HE4 levels were higher in the high-grade tumours than in the low-grade tumours (p<0.05). The area under the curve (AUC) for G3 diagnosis using multiparametric MRI combined with HE4 was 0.929. ADC values were significantly lower in the EAC with LVSI than in those without LVSI. Tumours with LVSI showed higher PEI and HE4 levels than those without LVSI (p<0.05). The AUC for LVSI-positive diagnosis using multiparametric MRI combined with HE4 was 0.814. CONCLUSION: Semi-quantitative DCE-MRI, ADC values, and serum HE4 levels can be used to predict tumour grade and LVSI, and the prediction efficiency of multiparametric MRI combined with serum HE4 is better than that of any single factor.

[Correlation between contrast-enhanced ultrasound parameters and Crohn's disease activity].

Objective: By investigating the correlation between quantitative parameters of contrast enhanced ultrasound (CEUS) and commonly used activity assessment indicators of Crohn's disease (CD), and comparing the predictive power of laboratory inflammatory indicators with CEUS on Crohn's disease (CD), the significance of CEUS was evaluated. Methods: A case-control study. From October 2019 to December 2021, the clinical data of 67 patients with CD who were diagnosed by endoscopy and underwent contrast-enhanced ultrasonography were retrospectively analyzed in the First Affiliated Hospital with Nanjing Medical University, and their routine ultrasound and CEUS parameters, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn's disease activity index (CDAI) and simplified endoscopic score for Crohn's disease (SES-CD) were collected. Using SES-CD as the standard, the patients were divided into a remission group and an active group, and the correlation of laboratory inflammatory indexes and contrast-enhanced ultrasound parameters with CDAI and SES-CD were evaluated. Besides, the ROC curve was used to analyze the predictive efficacy of each index on CD endoscopic activity. Results: A total of 67 patients were included in this study. According to the SES-CD score, there were 17 patients in the remission group and 50 patients in the active group. Except for the coefficient of the enhancement wash in slope and time to peak (TTP), the peak intensity (PI), area under the angiography curve, and laboratory inflammatory indexes were significantly different between the two groups (P<0.05), which also showed a moderate positive correlation with CDAI and SES-CD (P<0.05). ROC analysis showed that among the non-invasive indicators, PI and area under the angiography curve had the highest AUCs for predicting CD endoscopic activity, which were 0.912 and 0.891, respectively; with SES-CD taking >3 as the cut-off value, the corresponding sensitivities were 78.0% and 72.0%, with specificities of 100.0% and 94.1%, respectively. Conclusion: CEUS can objectively and repeatedly evaluate the disease activity of CD patients, and has great clinical application value, which can be used as a reliable imaging method for diagnosis and follow-up of patients with Crohn's disease.

A new prognostic model for brain metastases of specific primary tumors with stereotactic radiotherapy.

PURPOSE: Stereotactic radiotherapy (SRT) was widely used in brain metastases (BM), especially in oligometastases. It is imperative to develop a new prognostic score to predict the overall survival (OS) of brain metastases based on prognostic factors for specific primary tumors. MATERIAL AND METHOD: One hundred and ninety-seven patients were involved in the training cohort to develop a new prognostic score to predict the overall survival (OS) of brain metastases for specific primary tumors. Independent prognostic factors were confirmed using a Cox regression model. The score was developed based on clinical prognostic factors of OS with Cox proportional hazards model. The result was validated in another cohort with 56 participants to evaluate the performance of the score. RESULTS: One hundred and ninety-seven patients with 329 brain metastases received SRT. For NSCLC, the significant prognostic factors were extracranial metastases, target therapy and number of brain metastases. For gastrointestinal cancer, the significant prognostic factors were target therapy and number of brain metastases. CONCLUSION: The prognostic factors scores were varied by the histologic types which can be used to efficiently stratify for selected patients with brain-metastasis.

[The correlation between reflux esophagitis and Helicobacter pylori infection based on natural population].

Objective: Reflux esophagitis (RE) may be negatively correlated with Helicobacter pylori (H. pylori) infection, but the conclusion and relevant mechanism is still controversial. This study proposed to explore the correlation between RE and H. pylori infection based on natural population. Methods: From July 2013 to December 2014, 3 940 residents aged 40-69 years were recruited in Linqu County of Shandong Province and Hua County of Henan Province by the whole sampling method. All the subjects underwent gastroscopy, and gastric mucosa biopsy specimens were collected for pathological diagnosis and Warthin-Starry (WS) staining to identify H. pylori infection. Venous blood samples of some subjects were collected for H. pylori immunoglobulin G (H. pylori-IgG) detection. Also, demographic and sociological data were collected. Chi-square test and logistic regression were used to analyze the correlation between RE and H. pylori infection. Results: A total of 359 cases of RE were detected. Excluding RE and other upper gastrointestinal organic diseases, 3 382 cases were considered as controls. Chi-square test showed that WS staining positive rate in RE group was significantly lower than that in control group (P=0.023), but there was no significant difference in the positive rate of H. pylori-IgG between the two groups (P=0.281). There were significant differences between RE group and control group in gender composition, age, body mass index (BMI), smoking, alcohol consumption, education level and mucosal active inflammation. Multivariate regression analysis showed that RE was negatively correlated with gastric mucosa active inflammation [OR=0.754 (95%CI 0.600-0.949), P=0.016], and positively correlated with male [OR=4.231 (95%CI 3.263-5.486), P<0.001], age ≥60 years, BMI≥24 kg/m2 [OR=1.540 (95%CI 1.220-1.945), P<0.001]. Compared to those aged 40-49 years and 50-59 years, the odds ratio (OR) of RE in these aged ≥60 years were 1.566 (95%CI 1.144-2.143, P=0.005) and 1.405 (95%CI 1.093-1.805, P=0.008). Conclusion: RE is more closely related to H. pylori present infection. Multivariate analysis showed that RE is negatively correlated with active inflammation of gastric mucosa caused by H. pylori infection, and positively correlated with male, overweight and aged ≥60 years.

[Prognostic values of stromal tumor-infiltrating lymphocytes and lymphocyte-activation gene-3 in advanced gastric adenocarcinoma].

Objective: To analyze density of stromal tumor-infiltrating lymphocytes (sTIL) and expression of lymphocyte-activation gene-3 (LAG-3) protein in advanced gastric adenocarcinomas, and to investigate the correlation of sTIL and LAG-3 with the prognosis in patients with advanced gastric adenocarcinoma. Methods: The clinicopathological characteristics and follow-up data of 260 patients with advanced gastric adenocarcinoma were collected at Fujian Cancer Hospital, from January 2011 to December 2014. The percentage of sTILs was reported semi-quantitatively using histological section evaluation, the LAG-3 protein was detected using immunohistochemistry, and the expression was correlated with the clinicopathological features and patient outcomes. Results: Among the 260 cases, high density of sTIL was detected in 173 cases (66.5%) while LAG-3 high expression was observed in 160 cases (61.5%). These cases were divided into four groups. Group Ⅰ: 48 cases (18.5%) were sTIL low/LAG-3 low; group Ⅱ: 52 cases (20.0%) were sTIL high/LAG-3 low; group Ⅲ: 39 cases (15.0%) were sTIL low/LAG-3 high; group Ⅳ: 121 cases (46.5%) were sTIL high/LAG-3 high. Kaplan-Meier survival analyses showed that patient prognoses were related to age, tumor size, tumor location, Lauren classification, perineural invasion, vascular invasion, TNM staging, postoperative adjuvant chemotherapy and molecular classification (P<0.05). Meanwhile, higher densities of sTIL and higher expression of LAG-3 were associated with better prognosis. Multivariate survival analysis showed age, tumor size, Lauren classification and postoperative adjuvant chemotherapy were independent prognostic factors for patient survival. The results showed a poor prognosis in low-sTIL/low-LAG-3 patients. Conclusions: Compared with low density of sTIL and low expression of LAG-3, high density of sTIL and high expression of LAG-3 are associated with better outcomes in patients with advanced gastric adenocarcinoma, respectively. Combined detecton of sTIL and LAG-3 may be more useful in gastric cancer than using either alone. Age, tumor size, Lauren classification and postoperative adjuvant chemotherapy are independent prognostic factors for patients with advanced gastric adenocarcinoma.

Adenosine diphosphate-ribosylation factor-like 15 can regulate glycolysis and lipogenesis related genes in colon cancer.

This study was designed to investigate the potential key genes of ADP-ribosylation factor-like 15 (ARL15) regulating glycolysis and lipogenesis in colon cancer. Hematoxylin-eosin (HE) staining and immunohistochemistry were used to observe the expression of ARL15 in 10 normal colon tissues and 10 colon cancer tissues. Immunofluorescence staining was used to observe the expression position of ARL15 in normal human colorectal mucosa cells (FHC) and colon cancer cells (HCT116 and SW620) with a confocal microscope. The ARL15 plasmid and small interfering RNA (siRNA) were constructed. After transfection, the expression levels of glycolysis and lipogenesis regulatory enzymes and messenger RNA (mRNA) transcription of ARL15 in over-expressed and silenced colon cancer cells were detected by Western blotting and real-time quantitative PCR (qRT-PCR). High expression of ARL15 in colon cancer tissue and low expression in normal colon tissue, and all expression are in the cytosol. The expression position of ARL15 in the FHC, HCT116, and SW620 cells was consistent and mainly distributed in the cytosol. After the pCMV-3Tag-2-ARL15 plasmid was transfected in HCT116, the protein expressions of FASN, AKT, P-AKT, P-GSK, SREBP-1 (p125) (p<0.01), and AMPK (p<0.001) were higher than those in the control group. The mRNA transcription level of FASN, GSK, AMPKa1, and SREBP-1 gene was higher than control group after the over-expression of ARL15. After the ARL15-siRNA was transfected in HCT116, the protein expression levels of PKM2, PFK, FASN, AKT, P-AKT, P-GSK, and AMPK decreased compared with the control group, (p<0.05). The mRNA transcription level of FASN, GSK, AMPKα1 gene was lower than control group after the low-expression of ARL15 (p<0.05). After adding 2 µM JIB-04, ARL15 in HCT116 showed statistical differences compared with the control group at 12 h, 24 h and 36 h (p<0.05). After adding 2 µM JIB-04, the protein expression levels of AKT, p-GSK, FASN, AMPK and SREBP-1 in HCT116 cells decreased significantly after 24 h. It was also found that the expression levels of AKT, P-GSK, FASN, AMPK and SREBP-1 genes in the dose-adding group were significantly lower than those in the control group. In summary, ARL15 may promote the occurrence of colon cancer by increasing the expression of protein kinase B/AMP-activated protein kinase (AKT/AMPK) downstream regulatory enzymes for glycogenesis and lipogenesis. JIB-04 can target ARL15 and affect its expression as well as the expressions of glucose and lipid metabolity-related proteins in AKT and AMPK signaling pathways.

[Analysis of endoscopic and pathological features of gastric adenomatous polyps and risk factors for canceration].

OBJECTIVE: To investigate the endoscopic and pathological characteristics of gastric adenomatous polyps and to assess the potential risk factors for canceration of gastric adenomatous polyps. METHODS: The endoscopic and pathological characteristics of the patients with gastric adenomatous polyps from January 1, 2005 to December 31, 2019 were summarized retrospectively, and the risk factors of canceration were analyzed. RESULTS: A total of 125 patients with gastric adenomatous polyps were included, 51.20% of whom were females. The average age was (66.7±12.3) years. 64.80% of patients with gastric adenomatous polyps equal or more than 65 years old, and only 5.60% of the patients less than 45 years old. Adenomatous polyps were mostly distributed in the corpus and antrum with 40.80% and 32.80%, respectively. The majority of them were single (90.40%) and sessile (76.81%). 65.4% of adenomatous polyps were no more than 1.0 cm in diameter, and 23.20% of patients with adenomatous polyps were combined with hyperplastic polyps and/or fundus glandular polyps, and 1.60% had both pathological types of polyps. 58.62% (17/29) patients with hyperplastic polyps and/or fundus glandular polyps had multiple polyps. 1.60% (2/125) of the patients had gastric neuroendocrine tumor of G1 stage. Synchronous gastric cancer was detected in 13.60% (17/125) of the patients with adenomatous polyps, and the proportion of low-grade intraepithelial neoplasia was 18.40% (23/125). The main types of synchronous gastric cancer were progressive (70.59%) and undifferentiated (66.67%). Chronic atrophic gastritis with intestinal metaplasia was found in 52.80% of the patients, and autoimmune gastritis accounted for 11.20%. The positive rate of Helicobacter pylori was 21.60%. The canceration rate of gastric adenomatous polyps was 20.80%. The cancer was mainly differentiated, but there was sigmoid ring cell carcinoma as well. Diameter of >1.0 cm (OR=5.092, 95%CI: 1.447-17.923, P=0.011), uneven surface morphology and erosion (OR=13.749, 95%CI: 1.072-176.339, P=0.044) were independent risk factors of adenomatous polyps. CONCLUSION: The synchronous gastric cancer is common and the canceration of gastric adenomatous polyps is high with diameter and surface morphology as independent risk factors. We should pay attention to the identification of the pathological types of polyps and the evaluation of the whole gastric mucosa during the endoscopic examination.

[Genetic analysis of three cases of acephalic spermatozoa syndrome caused by SUN5 mutation and the outcome of assisted reproductive technology].

To explore the genetic causes of 3 male infertility patients with acephalospermia and the outcome of assisted reproductive technology. Clinical diagnosis, sperm morphology examination, sperm transmission electron microscopy examination were performed on 3 patients, and the whole exome sequencing technology was used for screening, Sanger sequencing verification, mutation pathogenicity analysis, and protein sequence homology comparison. Assisted reproductive technology was implemented to assist pregnancy treatment. The 3 patients were all sporadic infertile men, aged 25, 42 and 26 years, and there was no obvious abnormality in the general physical examination. Male external genitalia developed normally, bilateral testicles were normal in volume, and bilateral epididymis and spermatic vein were palpated without nodules, cysts, and tenderness. Repeated semen analysis showed that a large number of immature sperm could be seen, and they had the ability to move. The SUN5 gene of the 3 male infertile patients was a case of homozygous missense mutation c.7C>T (p.Arg3Trp), a case of compound heterozygous missense mutation c.1067G>A (p.Arg356His) and nonsense mutation c.216G>A (p.Trp72*) and a case of homozygous missense mutation c.1043A>T (p.Asn348Ile), of which c.7C>T (p.Arg3Trp) and c.1067G>A (p.Arg356His) were new variants that had not been reported. SIFT, Mutation Taster and PolyPhen-2 software function prediction results were all harmful, the nonsense mutation c.216G>A (p.Trp72*) led to the premature termination of peptide chain synthesis which might have a greater impact on protein function. The homology regions in the protein sequence homology alignment were all highly conserved.The 3 male patients and their spouses obtained 4 biological offspring through intracytoplasmic sperm injection, all of which were boys, and one of them was a twin.Three male infertile patients might be caused by SUN5 gene mutations. Such patients could obtain their biological offspring through assisted reproductive technology. It was still necessary to pay attention to the genetic risk of ASS, it was recommended that both men and women conduct genetic counseling and screening at the same time. In clinical diagnosis, whole exome sequencing technology could be used to perform auxiliary examinations to determine the treatment plan and assisted reproductive methods as soon as possible to reduce the burden on the family and society. The newly discovered mutation sites of SUN5 gene provided clues and directions for elucidating the pathogenic mechanism, and at the same time expanded the pathogenic mutation spectrum of ASS.

[Correlation of serum lipid profile and disease activity in patients with inflammatory bowel disease].

To analyze the correlation between lipid profile and disease activity in patients with inflammatory bowel disease (IBD).A total of 307 Crohn's disease (CD) patients, 232 ulcerative colitis (UC) patients and 165 healthy subjects from the same geographic region were included. Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a)[Lp(a)] were retrieved from their medical records. Crohn disease activity index (CDAI) and Mayo scores were calculated as measurement of disease severity for CD and UC separately. Patients with CD and UC had lower TC, TG, HDL-C and LDL-C levels than those in control group (P<0.05). Additionally, CDAI was negatively associated with TC, HDL-C and LDL-C levels (r=-0.218, -0.210, -0.176, P<0.05), while TG level was not associated with CDAI. Mayo scores was not significantly associated with TC, HDL-C, LDL-C and TG. Patients with CD had higher Lp(a) levels than those in UC and control group (P<0.05). Furthermore, patients with active CD had higher Lp (a) levels than those with inactive disease (P<0.05).The Lp(a) levels in CD patients were positively associated with CDAI (r=0.151, P<0.05), while Lp(a) level in UC group was nor assocriated with Mayo score. Patients with IBD have dyslipidemia and lipid profile is associated with disease activity in CD patients.

HPV16 infection promotes an M2 macrophage phenotype to promote the invasion and metastasis of esophageal squamous cell carcinoma.

OBJECTIVES: High-risk human papillomavirus (HR-HPV) is an important risk factor for esophageal cancer. Macrophages constitute a crucial immune medium for regulating HPV-related tumors; however, the specific regulatory mechanisms remain unknown. Therefore, the purpose of our current study was to investigate the mechanism by which HPV16E6 regulates macrophages to promote the invasion and metastasis of esophageal cancer. METHODS: HPV16E6 infection was detected by polymerase chain reaction. Immunohistochemistry was used to verify the distribution of tumor-associated macrophages (TAMs) and MMP-9 expression in esophageal squamous cell carcinoma tissues (ESCCs), and cancer adjacent normal tissues (CANs) from Kazakh patients. ESCC cells were transfected with a plasmid over-expressing HPV16E6 and non-contact cocultured with macrophages. RESULTS: The infection rate of HPV16E6 in Kazakh ESCCs was clearly higher than that in CANs (P < 0.05). The density of CD163-positive TAMs was significantly positively correlated with HPV16E6 infection in ESCCs (P < 0.05). After coculturing macrophages and EC9706 cells transfected with the HPV16E6 plasmid, the phenotype of macrophages transformed into M2 macrophages. The migration and invasion ability of ESCC cells were higher in the HPV16E6-transfected and coculture group than in the HPV16E6 empty vector-transfected and non-cocultured HPV16E6-transfected groups (all P < 0.05). The density of M2-like TAMs in ESCCs was positively correlated with the level of MMP-9 expression. MMP-9 expression in the HPV16E6-ESCC coculture macrophages group was substantially higher than that in controls (all P < 0.05). CONCLUSIONS: HPV16 infection mediates tumor-associated macrophages to promote ESCC invasion and migration.

Impact of insulin use on outcomes of diabetic breast cancer patients: a systematic review and meta-analysis.

OBJECTIVE: The study aimed to assess the impact of insulin use on outcomes of breast cancer patients with diabetes mellitus (DM). MATERIALS AND METHODS: Databases of PubMed, Embase, and CENTRAL were searched to identify all types of studies comparing mortality or recurrence between insulin and non-insulin DM patients with breast cancer. Adjusted hazard ratios (HR) were pooled for a meta-analysis. RESULTS: Eleven studies were included. Meta-analysis indicated a statistically significant increased risk of all-cause mortality in insulin users as compared to non-users (HR: 1.52 95% CI: 1.23 to 1.86 I2=83% p<0.0001). Our results also demonstrated a statistically significant increase in the risk of breast cancer mortality amongst insulin users as compared to non-users (HR: 1.33 95% CI: 1.08 to 1.63 I2=43% p=0.007). Only four studies assessed the impact of insulin therapy on recurrence rates. Meta-analysis indicated a statistically significant increased risk of breast cancer recurrence in insulin users vs. non-users (HR: 1.43 95% CI: 1.13 to 1.80 I2=0% p=0.003). Mortality results were stable on sensitivity analysis. CONCLUSIONS: Diabetic breast cancer patients on insulin have increased mortality and recurrence rates as compared to insulin non-users. Owing to the several limitations of the review, results should be interpreted with caution. Future studies should assess the impact of timing, duration, dosage, and type of insulin therapy on clinical outcomes.

Pharmacological characterization of three chicken melanocortin-3 receptor mutants.

The melanocortin-3 receptor (MC3R) is a G protein-coupled receptor and potentially important in production traits. Three naturally occurring mutations (M54L, G104S, and L151R) in chicken MC3R (cMC3R) were reported previously to be associated with production traits. Here, we inserted the full-length cMC3R coding sequence into pcDNA3.1(+) and generated the 3 mutations by site-directed mutagenesis. The total and cell surface expression of the receptors was measured by flow cytometry. We analyzed the pharmacological characteristics, including binding and cyclic adenosine monophosphate (cAMP) and mitogen-activated protein kinase (MAPK) signaling, using 6 ligands ([Nle4, D-Phe7]-α-melanocyte stimulating hormone (MSH), α-, ß-, γ-, and D-Trp8-γ-MSHs, and agouti-related peptide). All mutants had similar total and cell surface expression as the wild-type (WT) cMC3R. M54L had similar pharmacological properties as the WT cMC3R. G104S did not exhibit any specific binding but had minimal response to α-, ß-, γ-, and D-Trp8-γ-MSH, although it generated 24% WT response when stimulated by NDP-MSH. Although L151R had normal binding, the responses to agonists were reduced to approximately 25% of that of the WT. In MAPK signaling, all 3 mutants showed significantly increased agonist-stimulated phosphorylation of extracellular signal-regulated protein kinases 1/2, indicating the existence of biased signaling at G104S and L151R. In summary, our studies demonstrated that although all 3 mutations are significantly associated with production traits, only G104S and L151R had severe defects in receptor pharmacology. How M54L might cause production trait differences remains to be investigated.

[Retrospective analysis of 2 997 inpatients with skin and soft tissue injuries].

Objective: To analyze the epidemiological characteristics and the related information on the diagnosis and treatment of inpatients with skin and soft tissue injuries. Methods: The medical records of inpatients with skin and soft tissue injuries who were admitted to the Fourth Medical Center of PLA General Hospital (hereinafter referred to as the author's unit) from January 1, 2014 to December 31, 2018, conforming to the study criteria, were retrospectively analyzed. The indexes included inpatients'gender, age, wound course, underlying disease, wound type, wound site, and wound microbiological culture result, methods and outcome of treatment, type of medical payment, hospital day, and hospitalization cost. Data were statistically analyzed with Mann-Whitney U test, Kruskal-Wallis H test, and chi-square test. Results: (1) A total of 2 997 inpatients, conforming to the study criteria, were admitted to the author's unit during the 5 years. There were 1 803 (60.16%) males and 1 194 (39.84%) females. The distribution of gender of patients showed significant differences during the 5 years (χ(2)=13.203, P<0.05). The age of female patients was significantly older than that of male patients (Z=-6.387, P<0.01). There were 882 (29.43%) patients with acute wounds and 2 115 (70.57%) patients with chronic wounds. The distribution of acute wounds and chronic wounds of patients showed significant differences during the 5 years (χ(2)=66.806, P<0.01). The age of patients with chronic wounds was significantly older than that of patients with acute wounds (Z=-12.582, P<0.01). A total of 1 910 patients (3 847 cases) were complicated with underlying diseases. The common underlying diseases orderly were diabetes 1 151 (29.92%) cases, hypertension 884 (22.98%) cases, coro-nary atherosclerotic heart disease 414 (10.76%) cases, old cerebral infarction 258 (6.71%) cases, and paraplegia 258 (6.71%) cases. More patients with chronic wounds were complicated with various underlying diseases compared with patients with acute wounds (χ(2)=130.649, P<0.01). (2) The common types of wounds were postoperative non-healing wounds, burn wounds, diabetic foot ulcers, pressure ulcers, and skin and soft tissue infection. The distribution of types of wounds showed significant differences during the 5 years (χ(2)=342.265, P<0.01). There were 3 957 wounds. The common wound sites were feet, legs, chests, and so on. A total of 976 patients underwent microbiological examination. The results of 719 (73.67%) patients were positive and 257 (26.33%) patients were negative. The positive rate of wound microbiological culture of patients with chronic wounds was significantly higher than that of patients with acute wounds (χ(2)=33.981, P<0.01). Among the patients with acute wounds, 111 patients (72.08%) were simply infected, 43 (27.92%) patients were mixed infected. Among the patients with chronic wounds, 364 (64.42%) patients were simply infected, and 201 (35.58%) patients were mixed infected. A total of 1 010 strains of pathogenic bacteria were detected in 719 patients, including 447 (44.26%) Gram-positive bacteria, 548 (54.26%) Gram-negative bacteria, and 15 (1.48%) fungi. There was a significant difference in the distribution of pathogenic microorganisms between patients with acute wounds and chronic wounds (χ(2)=12.215, P<0.01). In this group of patients, the common strains of wounds were Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and so on. The common strains of patients with acute wounds were Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, and so on. The common strains of patients with chronic wounds were Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia colis, and so on. (3) The patients in this group were mainly treated by surgery. Finally, 1 330 patients were cured, 1 393 patients were improved, 257 patients were not cured, and 17 patients died. There was a significant difference in the distribution of outcome in patients with acute wounds and chronic wounds (Z=-7.622, P<0.01). (4) The main types of payment of medical expenses for patients in this group were local medical insurance, remote medical insurance, and self-paying. The total hospitalization cost of patients in this group was 169 268 523.65 yuan, which was mainly consist of the costs of materials and drugs. The hospital day of patients in this group was 21.00 (11.00, 36.00) d, and the hospitalization cost was 30 016.34 (14 439.41, 63 685.60) yuan. There were significant differences in the hospital day and hospitalization cost among patients with different medical payment types (χ(2)=285.986, 327.436, P<0.01). There were significant differences in the hospital day and hospitalization cost among patients with different wound types (χ(2)=125.912, 131.485, P<0.01). Conclusions: The patients with skin and soft tissue injuries are mainly middle-aged and elderly patients, with more males than females, more chronic wounds than acute wounds. Skin and soft tissue injuries are prone to occur in sites with prominent bone, thin subcutaneous fat, and poor blood supply. The result of wound microbiological culture is mainly Gram-negative bacteria, and the positive rate of wound microbiological culture of patients with chronic wounds is higher than that of patients with acute wounds. The proportion of Gram-positive bacterial infection ranks the highest in patients with acute wounds. The proportion of Gram-negative bacterial infection ranks the highest in patients with chronic wounds. Patients with chronic wounds are often complicated with various underlying diseases, and the course of disease is long, so the constituent ratio of cured patients is lower than that of patients with acute wounds. Patients with skin and soft tissue injuries have long hospital days and high proportion of material cost, which are directly related to the clinical characteristics and long treatment cycle of chronic wounds. Therefore, it is suggested that the medical insurance administration department should adjust the consumption ratio and other management indicators according to the actual clinical needs of elderly patients with chronic wounds.