[Gene expression signature analysis of peripheral blood mononuclear cells from patients with for high altitude pulmonary hypertension and value for potential drug selection].

Objective: To investigate the gene expression characteristics of peripheral blood mononuclear cells from patients with high altitude pulmonary hypertension (HAPH) in Naxi residents living in Lijiang, Yunnan, and to explore the underlying pathogenesis and value for potential drug selection. Methods: This is a case-control study. Six patients with HPAH (HPAH group) and 4 normal subjects (control group) were selected from the Naxi residents who originally lived in Lijiang, Yunnan Province. The general clinical data of the two groups were collected, and the related indexes of pulmonary artery pressure were collected. Peripheral blood mononuclear cells of the subjects were collected for RNA sequencing. The differences on gene expression, regulatory network of transcription factors and drug similarity between the two groups were compared. The results were compared with the public data of idiopathic pulmonary arterial hypertension (IPAH). Biological processes and signal pathways were analyzed and compared between HPAH and IPAH patients. Results: The age of 6 patients with HAPH was (68.1±8.3) years old, and there were 2 males (2/6). The age of 4 subjects in the control group was (62.3±10.9) years old, and there were 2 males (2/4). Tricuspid regurgitation velocity, tricuspid pressure gradient and pulmonary systolic pressure in HAPH group were significantly higher than those in control group (all P<0.05). The results of RNA sequencing showed that compared with the control group, 174 genes were significantly upregulated and 169 genes were downregulated in peripheral blood mononuclear cells of HAPH group. These differentially expressed genes were associated with 220 biological processes, 52 molecular functions and 23 cell components. A total of 21 biological processes and 2 signal pathways differed between HPAH and IPAH groups, most of which were related to inflammation and immune response. ZNF384, SP1 and STAT3 were selected as highly correlated transcription factors by transcription factor prediction analysis. Trichostatin A and vorinostat were screened out as potential drugs for the treatment of HAPH by drug similarity analysis. Conclusions: There are significant differences in gene expression in peripheral blood monocytes between HAPH patients and normal population, and inflammation and immune dysfunction are the main pathogenic factors. Trichostatin A and Vorinostat are potential drugs for the treatment of HAPH.

[The prevention and management of approach-specific complications of abdominal aortic balloon occlusion in pelvic and sacral surgery].

Objective: To investigate the causes,prevention and treatment of femoral artery puncture related complications caused by the application of resuscitative endovascular balloon occlusion of the aorta (REBOA) in the resection of pelvic and sacral tumors. Methods: Clinical data of 23 patients with femoral artery puncture related complications who received REBOA in the resection of pelvic and sacral tumors from August 2010 to August 2018 at the Musculoskeletal Tumor Center,Peking University People's Hospital were retrospectively analyzed.There were 8 males and 15 females,with the an age of (37.0±16.2) years (range:15 to 65 years).Arterial access via the Seldinger technique for REBOA was obtained in the right common femoral artery of 18 cases,and in the left of 6 cases.An arterial sheath with a diameter of 11 to 12 F(1 F≈0.33 mm) was used for the patient.The occurrence and treatment of postoperative complications were analyzed. Results: Acute femoral arterial thrombosis occurred in 18 patients,which was managed by open repair 48 hours postoperatively.Among the 349 patients admitted before 2015 who received hemostasis by compression after femoral artery sheath removal,12 patients (3.4%) developed acute femoral artery thrombosis.While the 476 patients admitted after 2015 who used a vascular stapler to close the femoral artery wound,6 patients (1.3%) developed acute femoral artery thrombosis.One case of retroperitoneal hematoma and 1 case of femoral pseudoaneurysm were found and surgically fixed.Postoperative follow-up was (40±18) months (range:13 to 108 months).Three cases with chronic lower extremity ischemia were confirmed by Doppler ultrasonography during 1 to 5 years follow-up.Two of them had minimal symptoms and denied further treatment,while the other one received femoral-femoral artery bypass surgery to restore distal flow for pain and numbness relief. Conclusions: Acute femoral arterial thrombosis was the most common femoral artery puncture.Technique refinement of REBOA,the use of percutaneous suture device and close follow-up can reduce the approach-specific complications,and help to detect and treat the complications timely,which may popularize the clinical application of REBOA.

Molecular characteristics of MC1R gene in tile-grey plumage of domestic chicken.

1. Tile-grey plumage is a unique and rare feather type of local chicken breeds in China, but its genetic mechanism and corresponding genes remain unknown. 2. In order to identify the genetic basis and molecular characteristics of tile-grey plumage, this experiment investigated variations of melanocortin 1 receptor (MC1R) gene in Yunnan Piao chickens with typical tile-grey plumage characteristics in contrast with three Yunnan local breeds as well as two standard breeds with different plumage colour, and analysed the association between genic variation and tile-grey plumage. 3. Through sequencing and comparison of the entire coding region of the MC1R gene, a total of 10 SNP loci were detected, of which eight were non-synonymous mutations that cause amino acid changes. The gene frequency and genotype frequency of the MC1R mutation sites in different breeds and different plumage colour groups revealed that C69T, T212C and A274G were significantly associated with tile-grey plumage. Eighteen haplotypes of the MC1R gene were constructed based on 10 nucleotide variations and eight amino acid variations. Haplotype distribution and the median joining network in breeds and plumage colour groups revealed a main haplotype (hap2) for tile-grey plumage. Hap2 is unique to the tile-grey feather of Piao chicken, and the individuals carrying this haplotype account for 62.96% of the whole tile-grey chicken. 4. The results of this study are of significance for further analysis of the molecular basis of tile-grey plumage and the selective breeding of tile-grey plumage.

[Significance of micropapillary histopathological subtype of thyroid carcinoma].

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group (P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion (P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without (P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.

[Comparison of radiological and clinicopathological features of craniofacial fibro-osseous lesions].

Objective: To investigate the clinicopathological and radiological features of benign fibro-osseous lesion (BFOL). Methods: Sixty-five cases of craniofacial BFOL, eight cases of peripheral ossifying fibroma (POF) and one case of low-grade central osteosarcoma diagnosed at Sichuan Provincial People's Hospital between January 2010 and March 2019 were collected. The clinicopathologic features, hematoxylin-eosin and immunohistochemical (IHC) staining and radiographic features were analyzed. MDM2 gene amplification was detected by FISH in difficult borderline cases. Results: This cohort of BFOLs included 50 cases of fibrous dysplasia (FD), 12 cases of ossifying fibroma (OF), and three cases of juvenile psammomatoid ossifying fibroma (JPOF). The average ages of patients with FD,OF and JPOF were 31.7, 39.2 and 26.0 years respectively. The male to female ratio was 1.0∶1.8.The average age of POF was 47.0 years, with male to female ratio of 1∶7. Patient of low-grade central osteosarcoma was a 48-year-old man. Twenty-seven cases of FD were located in the jaw, and 23 cases were in other craniofacial bones. Nine cases of OF were located in the jaw, and three cases were in the nasal cavity. Two cases of JPOF were in the nasal sinus, and one was in the jaw. All POF were located in the gingiva, and low-grade central osteosarcoma was located in the mandible. The imaging features of FD were luffa-like or ground-glass like signal shadows with poorly defined borders with expansion. OF had clear borders or sclerosing margins. Both JOF and low-grade central osteosarcoma were expansile intraosseously and with focally invasive nodular masses with ground-glass like signal shadows; and POF showed soft tissue mass with bone formation. Histological features of BFOLs showed mixed fibrous and irregular osteoid lesions. FD had no clear relationship with the host bone and no osteoblasts surrounded the bone trabeculae. Osteoblasts rimming was found in OF, and the boundaries of the host bone were clear. JPOF and low-grade central osteosarcoma infiltrated the host bone focally, and the latter showed mild cellular atypia. MDM2 amplification was detected in low-grade central osteosarcoma. Conclusions: BFOLs are a group of fibro-osseous lesions with similar morphology in the head and neck and face, but their clinical features and prognosis are different; and their imaging and histological characteristics are also slightly different. Attentions should be given to the combination of clinical, imaging and pathologic features of BFOLs, especially the differential diagnosis between BFOLs and low-grade central osteosarcoma. Molecular detection could be used to assist the diagnosis in difficult cases.

[Comparative study of functional prognosis of transanal total mesorectal excision and conventional total mesorectal excision based on propensity score matching].

Objective: To compare the postoperative functional prognosis of transanal mesorectal excision (taTME) and conventional total mesorectal excision (TME) in rectal cancer. Methods: Totally 49 patients underwent taTME and 478 patients underwent conventional TME at Department of Gastroenterological Surgery, Peking University People's Hospital from January 2015 to December 2019 were retrospectively collected. Propensity score matching method was used to perform 1 versus 1 matching between the taTME and conventional TME groups, and 36 pairs of patients were successfully matched. After matching, the median age of patients in taTME group and conventional TME group was 60.5 (16.0) years and 60.5 (13.0) years (M(Q(R))), respectively, and the proportion of male patients was 66.7% (24/36) and 55.6% (20/36) , respectively. EORTC QLQ-C30 scale was used to assess quality of life, low anterior resection syndrome (LARS) scale and Wexner constipation score were used to evaluate anal function, international prostate symptom score (IPSS) was used to evaluate urinary function,international index of erectile function (IIEF) -5 and female sexual function index (FSFI) score were used to evaluate male and female sexual function, respectively, and generalized anxiety disorder (GAD-7) and patient health questionnaire (PHQ-9) scale were used to evaluate psych function. The t test, Mann-Whitney U test, χ(2) test, and Fisher exact test were used for comparison between groups, and Wilcoxon rank sum test or McNemar test was used for comparison between paired data. Results: There were no significant differences in surgery time, postoperative hospital stays, conversion rate, morbidity rate, surgery cost, and numbers of lymph node yield between the two groups (all P>0.05). Compared with the conventional TME group, the intraoperative blood loss in the taTME group was significantly higher (100 (100) ml vs. 80 (50) ml, U=424.5, P=0.010), the prophylactic stoma rate was significantly higher (96.9%(31/36) vs. 63.6%(21/36), χ(2)=11.218, P<0.01), the total hospitalization cost was significantly lower (74 297.7 (16 746.4) CNY vs. 91 781.3 (26 228.4) CNY, U=413.0, P=0.008). There were no significant differences in anal and urinary function between the two groups (LARS scalescore: Z=-0.513, P=0.608, Wexner constipation score: Z=-0.992, P=0.321, IPSS: Z=-1.807, P=0.071). In terms of psych function, significant difference in GAD-7 scale was seen between the two groups (Z=-2.311, P=0.021), patients with generalized anxiety disorder accounting for 26.7% (8/30) and 46.9% (15/32), respectively. Conclusions: Compared with conventional TME surgery, taTME has a significantly increased blood loss and prophylactic stoma rate. There are no significant difference in the incidence of postoperative anal, urinary, and sexual dysfunction between taTME and conventinal TME. taTME can alleviate the financial burden and general anxiety disorder to a certain extent.

[Effects of intranasal dexmedetomidine for children undergoing dental rehabilitation under general anesthesia: a double-blinded randomized controlled trial].

OBJECTIVE: To observe the preoperative sedation, the status of separation from parents, compliance with the mask, hemodynamic parameters and postoperative agitation of intranasal dexmedetomidine (DEX) premedication on children undergoing dental rehabilitation under general anesthesia. METHODS: In the study, 60 children of American Society of Anesthesiology classification (ASA I-II), aged 2-9 years, were randomly assigned to one of two equal groups. Thirty minutes before operation, control group received intranasal placebo (0.9% saline) 0.02 mL/kg, and DEX group received intranasal DEX 2 µg/kg. The preoperative sedation score, the status of separation from parents, compliance with the mask and hemodynamic parameters were recorded by an anesthesiologists until anesthesia induction. Recovery conditions, postoperative agitation were also recorded. RESULTS: There was no significant difference between the two groups in patient characteristics, operation time, extubation time and recovery time. Compared with the children in control group, those in DEX group were significantly more sedated when they were separated from their parents (56.7% vs. 26.7%, P<0.05). Satisfactory compliance with mask application was 40% in control group vs. 73.3% in DEX group (P<0.05). There was no significant difference between the two groups regarding the incidences of postoperative agitation and oxygen saturation (SpO2). Compared with control group, the heart rate (HR) of DEX group was decreased after 20 minutes of drug administration [(97.13±12.93) beats/min vs.(104.53±11.97) beats/min, P<0.05]. The changes of the HR and SpO2 in the two groups were within the normal range. There were no incidences of bradycardia and hypoxemia in either of the groups during study observation. CONCLUSION: Premedication with intranasal DEX 2 µg/kg for children undergoing dental rehabilitation under general anesthesia produces good preoperative sedation. The levels of sedation, scores of parental separation and compliance with the mask were satisfied. The children have good recovery conditions, and no obvious postoperative agitation and respiratory depression after DEX administration. Intranasal DEX 2 µg/kg is an effective and safe alternative for premedication in children.

[Adenocarcinoma in a Meckel's diverticulum with multiple liver metastases and gastrointestinal hemorrhage: a case report].

Meckel's diverticulum is the most common congenital anomaly of the gastrointestinal tract, affecting approximately 2% of the population. It is a true diverticulum occurring on the anti-mesenteric border of the distalileum, typically within 100 cm of the ileo-caecal valve. Neoplasms arising in Meckel's diverticula are uncommon, and those reported in the literature are mainly carcinoid tumors, followed by gastrointestinal stromal tumors (GIST) and benign leiomyomas. Adenocarcinomas are extremely rare. Tumors in Meckel's present non-specifically with gastrointestinal complaints, such as bleeding, obstruction, inflammation or perforation. The suspicion of a Meckel's tumor is often not thought of at the initial. In this article we describe a 57-year-old woman who presented with massive rectal bleeding and severe anemia, later found to be caused by a adenocarcinoma arising from Meckel's diverticulum. The tumor was unfortunately highly aggressive. Multiple liver metastases had already existed when we discovered the primary mass. Later we performed a partial resection of the ileumto cease the bleeding. Meckel's diverticulum and the tumor were resected simultaneously. The pathological diagnosis confirmed adenocarcinoma arising from the Meckel's diverticulum. The final stage was pT4NxM1, stage IV according to the Union for International Cancer Control (UICC) classification. After operation we gave the patient first-line, mFOLFOX6 chemotherapy, but it turned out to be not effective. Rapid progress of the liver metastases and suspicion of multiple lung metastasis in short time after therapy indicated a bad outcome. We believe this is the first case of adenocarcinoma in a Meckel's diverticulum to be reported in domestic literature. The diagnosis of Meckel's tumor should be considered as inpatients'acute gastrointestinal complaints; when found incidentally at laparotomy, it should be carefully examined for any gross abnormality and resection should be considered.

[Efficacy and safety of drainage after total knee arthroplasty].

Objective: To determine whether suction drainage is safe and effective compared with no-drainage in total knee arthroplasty. Methods: The literature search was based on PubMed, MEDLINE, EMBASE, Highwire, the Cochrane Library, CBM, CNKI, VIP and WFSD.The data were analysed using RevMan 5.3.Fourteen randomised controlled trials involving 1 009 knees were included in our analysis. Results: Suction drainage increases the rate and volume of blood transfusion.No-drainage group increases the rate of wound problems (OR=1.92, 95%CI 1.21-3.04, P<0.05). No significant difference was observed in the incidence of periprosthetic infection (OR=0.68, 95%CI 0.20-2.30, P=0.54), VAS (OR=-0.09, 95%CI -0.32-0.14, P=0.46) and the length of stay (OR=0.41, 95%CI -0.21-1.03; P=0.19) when the drainage group was compared with the no-drainage group (P>0.05). Conclusions: No-drainage for easy total knee arthroplasty may be a better choice. However, orthopedic surgeon need to weigh the pros and cons of no-drainage in some complicated TKAs such as extra-articular deformity .

[The effect of complement C3a receptor antagonist in the kidney immune injury in trichloroethylene-sensitized mice].

Objective: To explore the effect of complement C3 a-C3a receptor in the kidney immune inju-ry in trichloroethylene-sensitized mice by using C3a receptor specific antagonist C3aRA and discuss the patho-genesis of kidney injury in occupational dermatitis medicamentosa-like of trichloroethylene (ODMLT) . Methods: 42 female 6~8 weeks old BALB/c mice of specific pathogen free were randomly divided into blank control group (5) , solvent control group (5) , TCE treatment group (16) and TCE+C3aRA treatment group (16) . The TCE treat-ment group and TCE+C3aRA treatment group were further divided into the sensitized group and the non-sensi-tized group according to the skin sensitization test score. Renal function was detected by biochemical detection kit; expression of C3aR in kidney tissue was detected by qPCR; expression of IL-1ß and TNF-α protein were de-tected by immunohistochemical. Results: Compared with solvent control group and corresponding non-sensitized group, CRE and BUN in TCE sensitized group and TCE + C3aRA sensitized group were significantly increased (P<0.05) . Compared with TCE sensitized group, CRE and BUN in TCE+C3aRA sensitized group were signifi-cantly decreased (P<0.05) . Compared with solvent control group and TCE non-sensitized group, the expression level of C3aR gene in kidney tissue in TCE sensitized group was significantly increased (P<0.05) . There was a large number of IL-1ß and TNF-α protein expression in kidney tissue in TCE sensitized group and TCE+C3aRA sensitized group. Compared with the TCE sensitized group, the expression level of IL-1ß and TNF-α protein in kidney tissue in TCE+C3aRA sensitized group was significantly decreased (P<0.05) . Conclusion: C3a-C3aR may be involved in the kidney immune injury in TCE sensitized mice, C3aRA has a protective effect on the kid-ney immune injury in TCE sensitized mice.

[Role of complement regulatory protein CD55 in the liver immune injury of trichloroethylene-sensitized mice].

Objective: To explore the expression of CD55 in liver tissue of trichloroethylene-sensitized mice and discuss the role of CD55 in the liver immune injury of trichloroethylene-sensitized mice. Methods: 6-8 weeks specific pathogen free female BALB/c were randomly divided into blank control group, solvent control group and TCE treatment group to establish BALB/c mice sensitized model. According to mouse skin sensitization reaction score, TCE treatment mice were divided into sensitized and non-sensitized group at 24 h after the last challenge. At 48 h after the last challenge, the blood and aseptic livers were collected. The level of serum ALT was tested by automatic biochemical analyzer and pathology of the liver was observed. C5b-9 deposition was studied by immunohistochemistry (IHC) . CD55 protein expression level in liver tissue was studied by immunohistochemistry and Western blotting. The expression of CD55 mRNA in liver tissue was detected by qRT-PCR. Results: Liver function test result showed level of serum ALT in TCE sensitized group was significantly higher than solvent control group and TCE non-sensitized group (P<0.05) . There was ballooning degeneration and necrosis of liver cells in TCE sensitized group. IHC demonstrated that TCE sensitized group had obviously increased content of C5b-9 but had reduced content of CD55 compared with solvent control group and TCE non-sensitized group (P<0.05) . Western blotting also showed that TCE sensitized group had lower expression of CD55 than solvent control group and TCE non-sensitized group (P<0.05) . qRT-PCR showed that CD55 mRNA expression level in liver tissue of TCE sensitized group was apparently lower than solvent control group and TCE non-sensitized group (P<0.05) . Conclusion: Complement activation may be involved in TCE-induced liver injury, and the expression change of complement regulatory protein CD55 may play essential role in the process.

Role of E3 ubiquitin ligases in insulin resistance.

E3 ubiquitin ligases are a large family of proteins that catalyse the ubiquitination of many proteins for degradation by the 26S proteasome. E3 ubiquitin ligases play pivotal roles in the process of insulin resistance and diabetes. In this review, we summarize the currently available studies to analyse the potential role of E3 ubiquitin ligases in the development of insulin resistance. We propose two mechanisms by which E3 ubiquitin ligases can affect the process of insulin resistance. First, E3 ubiquitin ligases directly degrade the insulin receptor, insulin receptor substrate and other key insulin signalling molecules via the UPS. Second, E3 ubiquitin ligases indirectly regulate insulin signalling by regulating pro-inflammatory mediators that are involved in the regulation of insulin signalling molecules, such as tumour necrosis factor-α, interleukin (IL)-6, IL-4, IL-13, IL-1ß, monocyte chemoattractant protein-1 and hypoxia-inducible factor 1α. Determining the mechanism by which E3 ubiquitin ligases affect the development of insulin resistance can identify a novel strategy to protect against insulin resistance and diabetes.

[Children's intelligence quotient following general anesthesia for dental care: a clinical observation by Chinese Wechsler young children scale of intelligence].

OBJECTIVE: It has been demonstrated that anesthetics exposure may lead to neurocognitive impairment in developing brain of animal models. However, for the limitation that the animal models cannot fully mimic the dose and duration in clinical settings especially for dental general anesthesia, the clinical significance of anesthetics exposure on developing central nervous system remains undetermined. Therefore, we conducted the current study in order to observe the fluctuation of intelligence quotient (IQ) after the administration of dental general anesthesia comparing to that before surgery. We conducted the current study in order to observe the fluctuation of intelligence quotient (IQ) after the administration of dental general anesthesia compared with that before surgery. METHODS: Thirty two patients, ASA I, who were exposed to dental general anesthesia in Department of Pediatric Dentistry Peking University School and Hospital of Stomatology, aged 4 to 6.5 years, were enrolled in this prospective study. Patients with severe learning difficulties or communication disorders were excluded. Written and informed consent was obtained from each patients' family which was fully explained of the purpose and method of study. Their intelligence quotients were evaluated with the Chinese Wechsler young children scale of intelligence (Urban version) before and 2 weeks after dental anesthesia. They were treated by experienced pediatric dentists and the sevoflurane, propofol and nitrous oxide were used for general anesthesia by anesthetist. Articaine hydrochloride and epinephrine tartrate injections were used for their pulp treatment or extraction. The examiners and scorers for IQ had technical training in the test administration. All the patients were tested by the same examiner and with standardized guide language. Each subtest was scored according to the tool review. Verbal IQ and performance IQ consisted of relevant 5 subtests and full scale IQ. Statistical analyses were performed by SPSS 18.0. All the scores of subtests and 3 types of IQ were expressed as mean±standard deviation. Paired two-tailed t test was applied and P<0.05 was accepted as statistically significant. RESULTS: The results of intelligent assessment from 28 subjects were collected. The anesthetic time was (163.4±32.6) min and the number of treated teeth was 12.1±2.3, mean age (4.60±0.41) years; age range=4.04 to 5.44 years. Among the patients, there were 13 girls and 15 boys. There was no significant difference in gender distribution. The postoperative full IQ (128.46±10.85) was higher than that before surgery (124.64±11.46, P= 0.017). We found that the elevation of performance IQ, to a large extent, contributed to this change in full IQ (P= 0.007). Correspondingly, there was no statistical difference in the verbal IQ, which was 119.68±11.74 to 120.21±15.61 (P=0.854). CONCLUSION: Dental general anesthesia has no negative effect on the intelligence of preschool children, who were treated under general anesthesia by sevoflurane, propofol and nitrous oxide for 2 to 4 hours. The full IQ and performance IQ were slightly enhanced after treatment which can be explained by the memory effect.

Link of obesity and gastrointestinal cancer: crossroad of inflammation and oxidative stress.

Obesity incidence has reached pandemic levels, and is accompanied by high incidence and poor prognosis of various types of cancers including gastrointestinal ones. Underlying mechanisms include elevated levels of insulin, IGF-I, and altered adipokine concentration, mainly towards leptin and adiponectin levels. However, it is not yet thoroughly understood. It is now widely known that obesity is associated with chronic low-grade inflammation, characteristic of altered immune cell infiltration in adipose tissue, and changed inflammatory cytokines and chemokines: tumor necrosis factor alpha (TNF-a), IL-6, and the chemoattractant monocyte chemoattractant protein 1 (MCP-1) and others, all together eventually promoting caner pathogenesis. Moreover, accumulating reports have shown that excess adipose tissue in obese individuals resulted in elevated levels of systematic oxidative stress, another way of promoting cancer development and progression. In general, altered immunological milieu and oxidative stress in obesity are important determinants for tumorigenesis.

Assessing the interactions between the associations of common genetic variants on 2q35 and 16q12 with breast cancer risk.

UNLABELLED: Genome-wide association studies (GWAS) have identified 2q35 and 16q12 as breast cancer (BC) susceptibility loci. However, the association between the two polymorphisms and BC remains controversial and inconsistent. We therefore performed a more precise estimation of these relationships by meta-analysing the currently available evidence from the literature. The PubMed, Ovid, Medline and Web of Science databases were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strengths of the associations. Thirty studies, including 106,312 cases and 140,939 controls, were identified. Overall, significantly elevated breast cancer risk was associated with the A allele of 2q35 rs13387042 when all studies were pooled into the meta-analysis (OR 1.11, 95%CI 1.07-1.15). Additionally, the T allele of 16q12 rs3803662 was associated with significantly increased breast cancer risk (OR 1.20, 95%CI 1.16-1.24). When stratifying for ethnicity, significantly increased risks were found among Caucasians, Asians and mixed ethnicities for both rs13387042 and rs3803662. For rs13387042, an association was observed for both oestrogen receptor-positive (ER+) (OR 1.14, 95%CI 1.11-1.17) and ER-negative (ER-) disease (OR 1.05, 95%CI 1.01-1.09) and for progesterone receptor-positive (PR+) (OR 1.16, 95%CI 1.12-1.19) and PR-negative (PR-) disease (OR 1.07, 95%CI 1.03-1.12). Similarly, a stronger association was observed for rs3803662 with ER+ tumors (OR 1.23, 95%CI 1.13-1.32) compared with ER- tumors (OR 1.08, 95%CI 0.97-1.20), and the same condition occurred for the polymorphism with PR+ tumors (OR 1.26, 95%CI 1.02-1.55) versus with PR- tumors (OR 1.15, 95%CI 0.90-1.46). When stratified by BRCA mutation status, a stronger association was observed with BRCA2 carriers (OR 1.23, 95%CI 1.05-1.44) than BRCA1 carriers (OR 1.09, 95%CI 1.04-1.15). In conclusion, this meta-analysis demonstrated that the A allele of 2q35 rs13387042 and the T allele of 16q12 rs3803662 are risk factors associated with increased breast cancer susceptibility. KEYWORDS: rs13387042, rs3803662, oestrogen receptor, progesterone receptor, breast cancer, meta-analysis.

Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.

We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.

[Etiology and clinical classification of constipation].

The causes of constipation are extremely complex and are still not fully clear. In addition to secondary factors such as organic diseases and drugs, constipation may also be related to genetics, diet, intestinal flora, age, gender and so on. At present, according to the etiology, chronic constipation is divided into primary constipation and secondary constipation. However, there are significant differences among current clinical guidelines in the clinical classification of primary constipation. Some guidelines classify primary constipation as slow-transit constipation (STC), outlet obstruction constipation (OOC), and mixed constipation; however, some guidelines classify primary constipation as STC, defecation disorder (DD), mixed constipation, and normal-transit constipation (NTC); what's more, some even propose types which are different from the above sub-types. There are also differences in the understanding of the relationship between functional constipation (FC) and primary constipation and the classification of irritable bowel syndrome predominant constipation (IBS-C) among various clinical guidelines. By reviewing domestic and international guidelines and relevant literature on constipation, the following conclusions are drawn: primary constipation can be divided into IBS-C and FC, and FC can be further divided into STC, OOC, and mixed constipation; primary constipation should not be confused with FC, nor should IBS-C be classified as FC.

Preoperative oral carbohydrates in elderly patients undergoing free flap surgery for oral cancer: randomized controlled trial.

The aim of this study was to evaluate the safety of carbohydrate intake 2 hours before surgery in elderly patients undergoing free flap surgery for oral cancer. Elderly patients undergoing free flap surgery between September 2019 and January 2021 were randomly divided into control (n = 43) and intervention (n = 43) groups. Control group patients fasted for 6 hours and were forbidden from drinking water for 4 hours before surgery. Intervention group patients fasted for 6 hours and were forbidden from drinking after the oral administration of 5 ml/kg carbohydrate (≤400 ml) 2 hours before surgery. The main outcome measures were aspiration, fasting blood glucose level, insulin concentration, insulin resistance index (fasting at admission, prior to anaesthesia induction, immediately after surgery, and at 6 a.m. on postoperative days 1 and 2), and comfort before and after surgery. No aspiration occurred in any of the patients during anaesthesia. There were significant differences in fasting blood glucose, insulin concentration, and insulin resistance index between the control and intervention groups prior to anaesthesia induction, immediately after surgery, and on day 1 after surgery (P < 0.01). Thirst (P = 0.001) and hunger (P = 0.003) differed significantly between the two groups prior to anaesthesia induction. The intake of oral carbohydrate 2 hours before surgery was both safe and effective for elderly patients with oral cancer undergoing free flap surgery and could relieve the physiological stress response.

[Effect of Echinococcus granulosus hydatid cyst fluid protein on allergic rhinitis induced by ovalbumin in mice].

OBJECTIVE: To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. METHODS: Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 µL sterile phosphate buffered saline (PBS), 200 µL sterile PBS containing 20 µg HCFP, 200 µL sterile PBS containing 50 µg OVA and 5 mg Al(OH)3 gel, and 200 µL sterile PBS containing 50 µg OVA, 5 mg Al(OH)3 gel and 20 µg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 µL sterile PBS, 40 µL sterile PBS containing 20 µg HCFP, 40 µL sterile PBS containing 2 mg OVA and 40 µL sterile PBS containing 2 mg OVA and 20 µL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-ß (TGF-ß) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. RESULTS: The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-ß (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-ß levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. CONCLUSIONS: E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.