High MCM6 expression promotes proliferation and correlates with poor prognosis in triple-negative breast cancer.

OBJECTIVE: Triple-negative breast cancer (TNBC) is an aggressive subtype with a poor prognosis. Minichromosome maintenance genes (MCM2-7) crucial for DNA replication are significant biomarkers for various tumor types; however, their roles in TNBC remain underexplored. MATERIALS AND METHODS: We utilized four TNBC-related GEO databases to examine MCM2-7 gene expression and predict its prognosis in TNBC, performing single-cell analysis and GSEA to discover MCM6's potential function. The Cancer Dependency Map gene effect scores and CCK8 assay were used to assess MCM6's impact on TNBC cell proliferation. The correlations between MCM6 expression, immune infiltrates, and immune cells were also analyzed. WGCNA and LASSO Cox regression built a risk score model predicting TNBC patient survival based on MCM6-related gene expression. RESULTS: MCM2-7 gene expression was higher in TNBC tissues compared to adjacent normal tissues. High MCM6 expression correlated with shorter TNBC patient survival time. GSEA and single-cell analysis revealed a relationship between elevated MCM6 expression and the cell cycle pathway. MCM6 knockdown inhibited TNBC cell proliferation. A risk model featuring MCM6, CDC23, and CCNB1 effectively predicts TNBC patient survival. CONCLUSIONS: MCM6 overexpression in TNBC links to a worse prognosis and reduced cell proliferation upon MCM6 knockdown. We developed a risk score model based on MCM6-related genes predicting TNBC patient prognosis, potentially assisting future treatment strategies.

[Factors associated with selection of breast-conserving surgery in early female patients with breast cancer].

Objective: To analyse the factors associated with the selection of breast- conserving surgery in early female patients with breast cancer. Methods: The targeted patients were females diagnosed with early-stage breast cancer and received surgical treatment at Fujian Provincial Hospital from January 1, 2015, to December 31, 2019. The targeted patients' clinical, demographic, and social-economic characteristics were extracted from the hospital health information system. Relevant information of their attending surgeons was collected through a smart-phone based self-respond online survey. We performed multivariate logistic regression to explore the associated factors with breast-conserving surgery (BCS) decision-making. Results: The age of the patient and attending surgeon and the economic development level of the patient's residence area were the associated factors with BCS decision-making of female early-stage breast cancer. By controlling the other factors unchanged, patients from middle-income areas were more likely to accept BCS (OR=1.91, 95%CI: 1.01-3.62, P=0.05) than those from low-income areas. When the attending surgeon was at the average age of 45 years old, increasing of 1 year age of patient led to 4% decrease of the probability of BCS (95%CI: -0.07 - -0.01, P=0.01). When the patient was at the average age of 52 years old, increasing of 1 year age of the attending surgeon reduced 10% of the probability of BCS (95%CI: -0.19 - -0.01, P=0.03). The interaction effects related to the age of attending surgeon and patient for some observations to choose BCS were statistically significant, and the average interaction effect was 0.06% (Z=2.11, sx =0.000 3, P<0.05). Conclusion: To promote breast-conserving surgery in the indicated early female patients with breast cancer, it is necessary to consider factors from both the surgeons and the patients.

The comparative safety of biological treatment in patients with axial spondylarthritis: a meta-analysis of randomized controlled trials with placebo.

OBJECTIVE: To evaluate the comparative safety of biological treatment in patients with axial spondyloarthritis (axSpA) enrolled in randomized controlled trials (RCTs) with placebo. MATERIALS AND METHODS: Studies were systematically retrieved from the Web of Science, PubMed, Cochrane Library, and Embase databases. The last search was performed on 8 June 2020. The primary outcome measures were adverse events (AEs), serious AEs, infection, serious infection, and discontinuation due to AEs. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of twenty-two trials, including 2599 participants treated with biologics and 1547 participants treated with placebo, met the inclusion criteria. There was a significantly higher risk of infection, AEs, and discontinuation due to AEs in the biologics groups compared to the placebo groups [risk ratio (RR) = 1.38, 95% confidence interval (95% CI) = 1.22-1.57, p < 0.01; RR = 1.17, 95% CI = 1.10-1.25, p < 0.01; and RR = 1.72, 95% CI = 1.03-2.87, p = 0.04, respectively], and low heterogeneity was found among the included studies (I2 = 0%, p = 0. 49; I2 = 29%, p = 0.10; and I2 = 0%, p = 0.79, respectively). The risk of serious infection and serious AEs was not significantly different between axSpA patients treated with biologics and those treated with placebo [RR = 1.62, 95% CI = 0.54-4.90, p = 0.39 and RR = 1.17, 95% CI = 0.79-1.73, p = 0.44]. Low heterogeneity was found among the included studies (I2 = 0%, p = 0.94 and I2 = 0%, p = 0.69). The subgroup analyses based on tumour necrosis factor inhibitors and interleukin antagonists did not yield significant differences. CONCLUSIONS: This meta-analysis is the first comprehensive assessment of the safety of various biological agents in axSpA patients. The use of biological agents in axSpA is generally safe and tolerable.

Prevalence of HIV indicator conditions in late presenting patients with HIV: a missed opportunity for diagnosis?

AIM: To evaluate prior prevalence of HIV indicator conditions in late-presenters with HIV infection. DESIGN: Retrospective cohort study between 2000 and 2014 in a healthcare network in Melbourne, Australia comparing patients presenting with late diagnosis of HIV infection (CD4 < 350 cells/ml) to those patients who had a CD greater than or equal to 350 cells/ml at presentation. METHOD: The European AIDS Clinical Society guidelines on HIV indicator guided testing were used to assess for any indicator conditions in their prior medical history which may have represented a missed opportunity for earlier diagnosis. Main outcome measures: Descriptive statistics and prevalence of HIV indicator conditions. RESULTS: Of 436 patients with HIV infection, 82 were late presenters. Late presenters were more commonly male (83% vs. 75%, P = 0.11), older (mean age 45 vs. 39 years), born overseas (61% vs. 58%, P = 0.68) and report heterosexual transmission as their exposure risk (51% vs. 31%, P < 0.001). Of 80 patients with late presentation of HIV infection, 54 (55%) had at least one, 29 (36%) at least 2, 12 (15%) at least 3 and 5 (6%) had 4 or more previous HIV indicator conditions which would have triggered HIV testing according to guidelines. The most common indicator conditions were: unexplained loss of weight (31%), herpes zoster (10%), thrombocytopenia or leukopenia (10%), oral or oesophageal candidiasis (10%) and community acquired pneumonia (9%). Twenty patients (25%) had HIV indicator conditions diagnosed at least 12 months before the eventual diagnosis of HIV infection. DISCUSSION/ CONCLUSION: Patients diagnosed with late-presenting HIV often had an HIV indicator condition prior to presentation, presenting a missed opportunity for earlier diagnosis.

High BMI has no impact on the survival of Chinese patients with lower thoracic esophageal adenocarcinoma treated with curative esophagectomy: a propensity score-matched study.

Controversy still exists as to whether a high body mass index (BMI) has any impact on the long-term survival of esophageal cancer patients treated with curative esophagectomy. Therefore, we conducted this propensity score-matched (PSM) study to explore the prognostic value of high BMI in Chinese patients with lower thoracic esophageal adenocarcinoma for the first time. We retrospectively collected data of patients with lower thoracic esophageal adenocarcinoma who underwent curative esophagectomy in our department from January 2009 to December 2016. Patients were grouped into high BMI group (≥23 kg/m2) and normal BMI group (18.5-22.9 kg/m2) according to the Asian specific BMI cutoff value. Both Cox regression survival analysis and PSM analysis were applied. Finally, a total of 132 patients were included for analysis. Fifty-three patients were in the high BMI group while 79 patients were in the normal BMI group. There was no significant difference regarding age, gender, comorbidity, tumor differentiation, tumor site, lymphovascular invasion, or surgical approaches between the two groups. However, patients with a high BMI tended to have more stage III diseases but a lower rate of adjuvant therapy application than those with a normal BMI. For survival, there was no significant survival difference between patients with a high BMI and those with a normal BMI (5-year overall survival (OS): 40.8% vs. 48.1%; P = 0.398). In the multivariate analysis, high BMI was not found to be an independent prognostic factor (HR = 1.028, 95%CI: 0.621-1.667, P = 0.945). A total of 92 well-matched patients were included after PSM analysis. However, there was still no significant difference of survival between the two groups (5-year OS: 41.4% vs. 43.3%; P = 0.760). Therefore, high BMI has no impact on survival of Chinese patients with lower thoracic esophageal adenocarcinoma treated with curative esophagectomy.

Does robot-assisted minimally invasive esophagectomy really have the advantage of lymphadenectomy over video-assisted minimally invasive esophagectomy in treating esophageal squamous cell carcinoma? A propensity score-matched analysis based on short-term outcomes.

This study aims to investigate advantages of robot-assisted minimally invasive esophagectomy (RAMIE) over video-assisted minimally invasive esophagectomy (VAMIE) in treating esophageal squamous cell carcinoma by applying propensity score-matched analysis. From April 2016 to January 2018, consecutive patients undergoing a McKeown RAMIE or VAMIE for esophageal squamous cell carcinoma were prospectively included for analysis. Baseline data, pathological findings, and short-term outcomes of the two groups (RAMIE group and VAMIE group) were collected and compared. Propensity score-matched analysis was applied to generate matched pairs for further comparison. Finally, we included a total of 151 patients (RAMIE group: 79 patients, VAMIE group: 72 patients) for analysis. In the analysis of unmatched cohort, RAMIE yielded a significantly larger number of total dissected lymph nodes (mean: 20.6 ± 8.8 vs. 17.9 ± 7.7; P = 0.048) and abdominal lymph nodes (mean: 9.5 ± 6.8 vs. 7.4 ± 5.1; P = 0.039) than VAMIE. However, there was no significantly different risk of major complications between the two groups. In the analysis of matched cohort, RAMIE still yielded a significantly larger number of total dissected lymph nodes (P = 0.006) and abdominal lymph nodes (P = 0.042) than VAMIE. There was still no increased risk of postoperative major complications in the RAMIE group compared to the VAMIE group. Moreover, RAMIE was found to yield significantly more left recurrent laryngeal nerve lymph nodes (mean: 1.0 ± 1.8 vs. 0.4 ± 0.8; P = 0.033) than VAMIE without increasing the risk of recurrent laryngeal nerve paralysis. Therefore, RAMIE may have the advantage of lymphadenectomy over VAMIE without increasing any risk of postoperative major complications. Further well-conducted studies, however, are needed to confirm our conclusions.

Comparison of short-term outcomes between robot-assisted minimally invasive esophagectomy and video-assisted minimally invasive esophagectomy in treating middle thoracic esophageal cancer.

Whether the robot-assisted minimally invasive esophagectomy (RAMIE) has any advantages over the video-assisted minimally invasive esophagectomy (VAMIE) remains controversial. In this study, we tried to compare the short-term outcomes of RAMIE with that of VAMIE in treating middle thoracic esophageal cancer from a single medical center. Consecutive patients undergoing RAMIE or VAMIE for middle thoracic esophageal cancer from April 2016 to April 2017 were prospectively included for analysis. Baseline data and pathological findings as well as short-term outcomes of these two group (RAMIE group and VAMIE group) patients were collected and compared. A total of 84 patients (RAMIE group: 42 patients; VAMIE group: 42 patients) were included for analysis. The baseline characteristics between the two groups were comparable. RAMIE yielded significantly larger numbers of total dissected lymph nodes (21.9 and 17.8, respectively; P = 0.042) and the right recurrent laryngeal nerve (RLN) lymph nodes (2.1 and 1.2, respectively; P = 0.033) as well as abdominal lymph nodes (10.8 and 7.7, respectively; P = 0.041) than VAMIE. Even though RAMIE may consume more overall operation time, it could significantly decrease total blood loss compared to VAMIE (97 and 161 mL, respectively; P = 0.015). Postoperatively, no difference of the risk of major complications or hospital stay was observed between the two groups. In conclusion, RAMIE had significant advantage of lymphadenectomy especially for dissecting RLN lymph nodes over VAMIE with a comparable rate of postoperative complications. Further randomized controlled trials are badly needed to confirm and update our conclusions.

Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells.

Vitamin D receptor (VDR) knockout (KO) mice had fewer Citrobacter rodentium in the feces than wild-type (WT) mice and the kinetics of clearance was faster in VDR KO than WT mice. VDR KO mice had more interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) and more antibacterial peptides than WT mice. The increased ILCs in the VDR KO mice was a cell-autonomous effect of VDR deficiency on ILC frequencies. Bone marrow (BM) transplantation from VDR KO mice into WT resulted in higher ILCs and colonization resistance of the WT mice. Disruption of the gut microbiota using antibiotics in VDR KO mice reversed colonization resistance to C. rodentium infection. Confirming the role of the microbiota in the colonization resistance of VDR KO mice, transfer of the VDR KO microbiota to WT germ-free mice resulted in colonization resistance. Once colonization resistance was overcome, VDR KO mice had increased susceptibility to C. rodentium. VDR expression is a regulator of ILC frequencies, IL-22, dysbiosis, and C. rodentium susceptibility.

Genetic variation in the LMP/TAP gene and outcomes of hepatitis B virus infection in the Chinese population.

Genetic polymorphisms of the LMP/TAP gene coded by the HLA-II region may be associated with outcomes of HBV infection. We conducted a case-control study to test the hypothesis, including a persistent group of 155 patients with chronic hepatitis B and 36 healthy carriers, a recovered group of 165 individuals spontaneously recovered from HBV infection, and an uninfected group of 278 healthy normal controls. Genotypes of eight polymorphisms of the LMP/TAP gene were analysed by PCR-RFLP. A logistic regression model was used to analyse statistical differences in polymorphisms or haplotypes in different groups. Of the eight polymorphisms, two (TAP1 codon 637 and LMP7 codon 145) were observed to have statistically significant association with outcomes of HBV infection (P<0·05). The two-locus haplotype constructed with two such polymorphisms was analysed. The frequencies of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were found to be increased significantly in the persistent group, compared to healthy controls (OR 2·26, 95% CI 1·62-3·15, P<0·001; OR 2·37, 95% CI 1·69-3·32, P<0·001; OR 4·38, 95% CI 1·78-10·77, P=0·001, respectively). The prevalence of haplotypes B (Asp-Lys), C (Gly-Gln), and D (Gly-Lys) were also significantly higher in the persistent infectious group than in the recovered group (OR 2·68, 95% CI 1·81-3·98, P<0·001; OR 2·40, 95% CI 1·62-3·55, P<0·001; OR 3·03, 95% CI 1·22-7·55, P=0·017, respectively). These findings indicated that genetic polymorphisms of the LMP/TAP gene might be an important factor in determining the outcome of HBV infection.

Management of delayed intrathoracic esophageal perforation with modified intraluminal esophageal stent.

In this article, we reviewed our experience of treatment of the delayed intrathoracic nonmalignant esophageal perforation employing modified intraluminal esophageal stent. Between February 1990 and August 2006, eight patients were included in this study. Five patients experienced sepsis. The interval time between perforation and stent placement ranged from 36 h to 27 days (average, 8.6 days). Esophageal stenting and throracotomy for foreign body removal were performed in four patients. The remaining four patients underwent stent placement and thoracostomy. Nutrition was initiated through gastrostomy after 7 to 10 days after the stenting. The stent was removed after the patients resumed oral intake of food and the esophagogram showed that perforation was closed. There was no death in this group. Signs of sepsis remitted 1 week after stent placement. Complications included stress ulcer, stimulative cough, and pneumonia each. Stent removal ranged 32 to 120 days (average 66.7) after its placement. The stent was kept in place for 4 months to prevent formation of esophageal stricture in one patient with caustic esophageal burns. The follow-up was completed in all the patients. The mean follow-up period was 59 months (range 12-180). One patient with caustic esophageal burn underwent cicatricial esophagectomy and gastric transposition 3 years later due to the esophageal stricture. Barium swallow demonstrated that there was a diverticulum-like outpouching in one patient and slight esophageal stricture at T2 and T3 level in another. One patient developed reflux esophagitis 5 years after stent removal. All the patients finally had a normal intake of food. Modified esophageal stenting is an effective method to manage the delayed intrathoracic esophageal perforation. Prevention of stent migration and its convenient adjustment might be the major advantages of this method.

Autonomic neuropathy precedes cardiovascular dysfunction in rats with diabetes.

BACKGROUND: Our team previously demonstrated arterial stiffening and cardiac hypertrophy in type 2 diabetic rats at 8 but not 4 weeks after being administered streptozotocin (STZ) and nicotinamide (NA). The present study focused on investigating the effects of type 2 diabetes on cardiac autonomic nerve function in the STZ- and NA-treated animals, using modern spectral estimation technique. DESIGN: An autoregressive process was performed to each detrended signal of heart rate and systolic blood pressure measured in the 4- and 8-week STZ-NA rats with anaesthesia. The power of low-frequency and high-frequency oscillations was automatically quantified with each spectral peak by computing the residuals. The closed-loop baroreflex gain was estimated using the square root of the ratio between heart rate and systolic blood pressure powers in the low-frequency band. RESULTS: Compared with the age-matched controls, both the 4- and 8-week STZ-NA diabetic rats had significantly decreased low-frequency oscillations of heart rate but not systolic blood pressure variability, showing a decline in baroreflex gain (0.451 +/- 0.060 and 0.484 +/- 0.056 vs. 1.196 +/- 0.064 ms mmHg(-1), P < 0.05). On the other hand, the low frequency-high frequency power ratio of the heart period was also diminished in the two diabetic groups, indicating a shift in sympatho-vagal balance of the heart control (0.472 +/- 0.109 and 0.504 +/- 0.090 vs. 1.857 +/- 0.336, P < 0.05). CONCLUSIONS: The cardiac autonomic dysfunction in the absence of any significant changes in vascular dynamics, 4 but not 8 weeks after induction of type 2 diabetes, suggests that the diabetic autonomic neuropathy may precede arterial stiffening and cardiac hypertrophy in the STZ- and NA-treated rats.

Aminoguanidine prevents the impairment of cardiac pumping mechanics in rats with streptozotocin and nicotinamide-induced type 2 diabetes.

BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been shown to prevent arterial stiffening and cardiac hypertrophy in streptozotocin (STZ) and nicotinamide (NA)-induced type 2 diabetes in rats. Our aims were to examine whether AG produced benefits on cardiac pumping mechanics in the STZ and NA-treated animals in terms of maximal systolic elastance (E(max)) and theoretical maximum flow (Q(max)). EXPERIMENTAL APPROACH: After induction of type 2 diabetes, rats received daily injections of AG (50 mg kg(-1), i.p.) for 8 weeks and were compared with age-matched, untreated, diabetic controls. Left ventricular (LV) pressure and ascending aortic flow signals were recorded to calculate E(max) and Q(max), using the elastance-resistance model. Physically, E(max) reflects the contractility of the myocardium as an intact heart, whereas Q(max) has an inverse relationship with the LV internal resistance. KEY RESULTS: Both type 2 diabetes and AG affected E(max) and Q(max), and there was an interaction between diabetes and AG for these two variables. The E(max) and Q(max) were reduced in rats with type 2 diabetes, but showed a significant rise after administration of AG to these diabetic rats. Moreover, the increase in Q(max) corresponded to a decrease in total peripheral resistance of the systemic circulation when the STZ and NA-induced diabetic rats were treated with AG. CONCLUSIONS AND IMPLICATIONS: AG therapy prevented not only the contractile dysfunction of the heart, but also the augmentation in LV internal resistance in rats with STZ and NA-induced type 2 diabetes.

Prevention and management of complications after colon interposition for corrosive esophageal burns.

We present our experience in the management of complications after a colon interposition for corrosive esophageal burns. From April 1976 to December 2006, 85 patients with caustic esophageal burns were included in this study. The superior belly median incision with an anterior border incision of the left sternocleidomastoid was used. Anastomosis between the colon and the cervical esophagus was performed in 68 and between the colon and pharyngeal portion in 14 patients. An esophageal scar part resection and gastric-esophageal anastomosis was performed in one patient who had been given an unsuccessful colon and jejunum interposition at another institute. An anastomotic modeling operation was performed in one patient with anastomotic stricture who had been managed with colon interposition at another institute. Exploratory thoracotomy and gastrostomy was performed in one patient who had an unsuccessful colon interposition at another institute. Seven of 14 patients (8.5% of 17.1%) died with serious complications such as aspirated pneumonia, interposition colon necrosis, abdominal wound dehiscence and degradation of swallowing and concordance function. However, others with such serious complications survived and were discharged for rehabilitation after corresponding treatment. The 25 patients (30.1%) with other mild complications were discharged for rehabilitation and corresponding management. Two patients from other institutes were discharged for rehabilitation and one was lost to follow-up. The most dangerous complication of this procedure is colon necrosis, and the stomach is the best organ for re-operation. Otherwise, aspiration in infants due to hypoplasia and degradation of swallowing co-ordination needs attention. Peri-operative management is very important, including the control of mediastinal and pulmonary infection and systemic nutritional support to avoid abdominal wound dehiscence. The platysma flap is an excellent method for the treatment of anastomotic stricture.

Lactococcus garvieae infection in the giant freshwater prawn Macrobranchium rosenbergii confirmed by polymerase chain reaction and 16S rDNA sequencing.

An epizootic bacterial infection in the giant freshwater prawn Macrobranchium rosenbergii occurred in Taiwan from May to June 1999. The cumulative mortality was approximately 30 to 75%. The diseased prawns showed opaque and whitish muscles and were approximately 2 mo old with total lengths from 5 to 6 cm. Histopathologically, they showed marked edema and necrotic lesions with inflammation in the muscles and hepatopancreas. Bacteria isolated using brain heart infusion medium or tryptic soy agar were Gram-positive and ovoid. Three isolates from diseased prawns at different farms were tested using the API 20 Strepsystem and conventional tests and identified as Lactococcus garvieae. Experimental infections with these isolates gave gross signs and histopathological changes similar to those seen in the naturally infected prawns. The LD50 value of isolate MR1 was 6.6 x 10(5) colony forming units/prawn. Identification of MR1 was confirmed by a PCR assay for L. garvieae that gave the expected amplicon of 1100 bp. In addition, its 16S rDNA sequence (GenBank accession number AF283499) gave 99% sequence identity to Enterococcus seriolicida (synonym L. garvieae; GenBank accession number AF061005). This is the first report of confirmed L. garvieae infection in prawn aquaculture.

Preamplifier with a second-order high-pass filtering characteristic.

A new preamplifier for suppressing low-frequency interference is presented. The proposed preamplifier, with its front end being implemented by an instrumentation amplifier, enjoys the following advantages: differential high-pass filtering, high input impedance, high common--mode rejection ratio and low passive sensitivity. This circuit can be realized with commercial operational amplifiers with enough phase margin, or fabricated in a chip for practical measurement of physiological signals.

Evaluation of the dose to the bladder wall using a dynamic balloon-bladder phantom and TLD measurements in 18F-FDG PET studies.

[18F]-2-deoxyglucose (18F-FDG) is one of the most useful radiopharmaceuticals in clinical positron emission tomographic imaging. Its final metabolic destination is the bladder, which accumulates the highest absorbed dose in the body during imaging. The aims of this study were to develop a dynamic bladder phantom to emulate the dynamic response of the bladder and to evaluate changes in the dose to the bladder wall during the imaging procedure. 18F-FDG of various concentrations can be drip-fed intravenously to the balloon-bladder at different uptake phases or extracted from the phantom during voiding. A dose evaluation model, introducing the concept of photon energy flux conversion into the dose calculation, is thus developed for clinical evaluation. The dose to the bladder wall using the proposed model is comparable to that measured using a thermoluminescence dosimeter (TLD), with a less than 5% discrepancy. The main advantages of the model are the use of the dose conversion factor, phi TLD, which is determined from real TLD measurements, and the ability to consider the dynamic characteristics of the bladder. To overcome the problems of diverse dose distributions among subjects, time-activity information provided by clinical bladder imaging is required, so that the method can be applied to other radiopharmaceuticals.