Experimental Limits on Solar Reflected Dark Matter with a New Approach on Accelerated-Dark-Matter-Electron Analysis in Semiconductors.

Recently a dark matter-electron (DM-electron) paradigm has drawn much attention. Models beyond the standard halo model describing DM accelerated by high energy celestial bodies are under intense examination as well. In this Letter, a velocity components analysis (VCA) method dedicated to swift analysis of accelerated DM-electron interactions via semiconductor detectors is proposed and the first HPGe detector-based accelerated DM-electron analysis is realized. Utilizing the method, the first germanium based constraint on sub-GeV solar reflected DM-electron interaction is presented with the 205.4 kg·day dataset from the CDEX-10 experiment. In the heavy mediator scenario, our result excels in the mass range of 5-15 keV/c^{2}, achieving a 3 orders of magnitude improvement comparing with previous semiconductor experiments. In the light mediator scenario, the strongest laboratory constraint for DM lighter than 0.1 MeV/c^{2} is presented. The result proves the feasibility and demonstrates the vast potential of the VCA technique in future accelerated DM-electron analyses with semiconductor detectors.

[Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation].

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

[Design of an improved percutaneous transhepatic cholangio drainage tube based on MRCP imaging data].

Objective: Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube. Methods: 3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length. Results: In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice. Conclusion: MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.

[Applications and challenges of pathomics technique in the management of hepatocellular carcinoma].

The incidence and mortality rate of hepatocellular carcinoma rank among the top of all cancer types,seriously threatening the life and health of human beings. In recent years,the rapid development of artificial intelligence and the deepening of the concept of precision medicine have led to a boom in interdisciplinary research. Pathomics,as an emerging omics technology driven by artificial intelligence,can mine massive information from high-resolution whole slide images,and shows broad application prospects in the diagnosis,treatment and prognosis assessment of hepatocellular carcinoma. However, pathomics research in hepatocellular carcinoma is still in its infancy, and its research patterns and clinical applications still face several controversies and challenges, including data security, ethics, and "black box" issues. Future research should focus on conducting prospective studies, integrating multimodal data, improving computational technologies, and establishing professional standards to promote the high-quality development of pathomics technology in both clinical and basic research of hepatocellular carcinoma.

[Arrhythmias and electrocardiographic characteristics in cancer patients treated with immune checkpoint inhibitors].

Objective: To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs). Methods: This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes. Results: A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment (P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions: The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

[Comprehensive clinical evaluation of bedaquiline in the treatment of multidrug-resistant tuberculosis].

Objective: To assess the clinical value of bedaquiline in five dimensions: effectiveness, safety, economics, appropriateness, and social benefits, to provide a reference for medical and health insurance-related decisions. Methods: A total of 792 patients with multidrug-resistant tuberculosis who were hospitalized at Wuhan Pulmonary Hospital, Ganzhou Fifth People's Hospital and Jiangxi Chest Hospital between January 2018 and December 2020 were included in the study. Based on a retrospective survey of case data, and each evaluation dimension of bedaquiline was statistically analyzed by causal analysis or chi-square test, using linezolid as the reference drug. Results: In terms of effectiveness, bedaquiline significantly increased treatment success by 23.9% (95%CI:4.8%-43.0%) and shortened treatment duration by 64 days(95%CI:18-109 days). In terms of safety, the incidence of adverse reactions to bedaquiline and the discontinuation rate of adverse reactions (5.11%,4.55%) were significantly lower than those for linezolid (22.49%,15.24%), with statistically significant differences (χ2=27.50,P<0.001;χ2=14.09,P<0.001). In terms of economics, patients treated with bedaquiline had a significantly higher anti-TB drug course cost of RMB 48 209.4 Yuan(95%CI: 28 336.0-68 082.8 Yuan). In terms of appropriateness, the proportion of bedaquiline in patients' initial treatment regimens was lower than that of linezolid (16.7% vs. 86.5%) in the 2020 observation sample, with a statistically significant difference (χ2=238.96,P<0.001). In terms of social benefits, the infection control rate was significantly increased by 27.8% (95%CI:8.2%-47.5%) in patients using bedaquiline. Conclusions: Bedaquiline performed well in terms of efficacy, safety, and social benefits. However, it was less economical and the actual use rate of bedaquiline in clinical practice was lower than that of its counterpart drug, linezolid. Price reductions might be needed to increase the clinical use and performance of bedaquiline in the future.

[Investigation on reproductive health status of women workers in different positions in oilfield enterprises].

Objective: The status and influencing factors of reproductive health (including menstrual period and gynecological diseases) of female workers in different positions of oilfield enterprises were analyzed. Methods: From January to December 2020, a total of 979 female workers in an oil field were selected as research objects by the judgment sampling method, and the "Female Reproductive Health Survey" was used as the investigation tool to investigate the demographic characteristics, menstrual status and gynecological diseases. The influential factors were analyzed by 2-test and logistic regression analysis. Results: The prevalence of abnormal menstruation was 26.1% (256/979), dysmenorrhea 53.1% (520/979), and gynecological diseases 54.34% (532/979). The prevalence of breast disease was 23.39% (229/979), uterine disease 11.03% (108/979), cervical disease 10.32% (101/979), and HPV infection 7.97% (78/979). Age, the nature of the job and whether occupational harmful factors were clear were the influencing factors of gynecological diseases (P=0.001, 0.000, 0.007). Age, job nature, working hours and work intensity were the influencing factors of abnormal menstruation (P=0.005, 0.000, 0.000, 0.010) . Conclusion: The reproductive health status of female workers in different positions of oil field enterprises is not optimistic, and the reproductive health status of female workers in professional and technical positions needs to be improved.

Constraints on Sub-GeV Dark Matter-Electron Scattering from the CDEX-10 Experiment.

We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.

Exotic Dark Matter Search with the CDEX-10 Experiment at China's Jinping Underground Laboratory.

A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.

[Current status of liver transplantation for adult patients with acute-on-chronic liver failure].

Acute-on-chronic liver failure(ACLF) is the most severe form of acute decompensation that develops in patients with chronic liver disease or liver cirrhosis,and is always accompanied by one or more extrahepatic organ failure, and has an extremely poor short-term prognosis. The causes triggering ACLF are complex and diverse,and the clinical stage and the type and the definition of organ failure differ greatly from one another. Therefore, a universally accepted diagnostic criteria for ACLF is not to be defined, and the epidemiological data and patient outcomes on ACLF are not easy to predict and compare among different regions. Accumulating evidence has shown that liver transplantation(LT) plays a significant role in the surgical treatment of patients with ACLF,but its clinical value is still controversial. The specific management and treatment strategy after the admission of patients with ACLF has not yet formed a unified and standardized process or opinions, which includes the monitoring in the ICU,the support and maintenance of organ functions, the selection of the surgical indication and the timing for LT and so on. Moreover, there still exists many controversies concerning, for example, whether patients with ACLF should receive greater priority for organ allocation compared to other potential candidates on the waiting list. Besides, more prospective controlled studies are urgently needed to investigate the role of the artificial liver support system in the bridging therapy to LT. The aim of this article is to review the indication selection of patients with ACLF suitable for LT,the survival outcomes and prognostic factors after LT, the selection of timing, the organ allocation policy and the bridging therapy to LT, which intends to provide new direction for designing the future clinical studies on LT in patients with ACLF.

[Comparison of alignment and operative time between portable accelerometer-based navigation device and computer assisted surgery in total knee arthroplasty].

OBJECTIVE: To explore the differences of alignment and operative time between portable accelerometer-based navigation device (PAD) and computer assisted surgery (CAS) in total knee arthroplasty (TKA). METHODS: Data of patients using iASSIST (a kind of PAD) and OrthoPilot (a kind of CAS) for TKA in Peking University Third Hospital from December 2017 to December 2019 were retrospectively collected. The differences of preoperative general data, preoperative alignment, operative time and postoperative alignment were studied between the two groups. RESULTS: A total of 82 patients were enrolled in our study, including 40 patients in the PAD group and 42 patients in the CAS group. Gender, age, body mass index (BMI), surgical side, preoperative hip-knee-ankle (HKA) angle and preoperative HKA angle deviation didn't show statistically significant difference between the PAD group and the CAS group (P>0.05). Postoperative HKA angle (180.8°±2.2° vs.181.8±1.6°, t=－2.458, P=0.016) and postoperative coronal femoral-component angle (CFA, 90.6°±1.8° vs. 91.6°±1.6°, t =－2.749, P=0.007) of the PAD group were smaller than those of the CAS group, but there was no significant difference in coronal tibia-component angle (CTA, 90.0°±1.3° vs.89.6°±1.4°, t=1.335, P=0.186) between the two groups. There was no significant difference in the rate of outliers (varus or valgus > 3°) for postoperative HKA angle (10.0% vs.11.9%, χ2 =0.076, P=0.783), CFA (12.5% vs. 14.3%, χ2=0.056, P=0.813) and CTA (2.5% vs. 0%, χ2=1.063, P=0.303). There was no significant difference in the accuracy of postoperative HKA angle (2.1° vs. 2.0°, t=0.055, P=0.956), CFA (1.4° vs. 1.8°, t=－1.365, P=0.176) and CTA (1.0° vs. 1.1°, t=－0.828, P=0.410) between the two groups. The precision of postoperative HKA angle (1.1° vs. 1.3°, F=1.251, P=0.267), CFA (1.3° vs. 1.4°, F=0.817, P=0.369) and CTA (0.8° vs. 0.9°, F=0.937, P=0.336) were also not significantly different. We also didn't find statistically significant difference in operative time between the two groups [(83.4±25.6) min vs. (86.5±17.7) min, t=－0.641, P=0.524]. CONCLUSION: PAD and CAS had similar accuracy and precision in alignment in TKA, and there was no significant difference in operative time, which indicates that PAD has a broad application prospect in TKA.

[Surgical diagnosis and treatment of adult huge undifferentiated embryonal sarcoma of the liver].

Objective: To investigate the clinical characteristics of adult undifferentiated embryonal sarcoma of the liver (UESL). Methods: A retrospective analysis was performed on the clinical data of 5 patients with UESL who underwent surgical resection and were pathologically confirmed from January 2005 to December 2020 at the First and the Second Affiliated Hospital of Anhui Medical University. All the patients were female aged from 49 to 77 years old. Preoperative CT showed a solid cystic mass with low density and a slight density of cord like septum. Imaging findings were misdiagnosed as hepatocellular carcinoma or cystadenocarcinoma. CA125 was higher in 3 patients,and AFP in all patients was normal. Results: All patients were treated by surgery. The mean diameter of tumor was 20.2 cm (range:15.0 to 30.0 cm). All five patients had vimentin expression in immunohistochemistry. Three cases underwent complete resection of the tumor and achieved R0 resection,2 of them had tumor free survival until the end of the follow-up (89 and 55 months),the other 1 case died from renal cell carcinoma 158 months later. The remaining 2 cases were radically resected,but the tumors were ruptured during operation,and relapsed after 2 months and 19 months respectively. The overall survival was 3 and 26 months respectively. Conclusions: Radical hepatectomy is the first choice for treatment of UESL. Intraoperative tumor rupture should be avoided and implant metastasis is a major factor affecting the prognosis of UESL.

Direct Detection Constraints on Dark Photons with the CDEX-10 Experiment at the China Jinping Underground Laboratory.

We report constraints on the dark photon effective kinetic mixing parameter (κ) with data taken from two p-type point-contact germanium detectors of the CDEX-10 experiment at the China Jinping Underground Laboratory. The 90% confidence level upper limits on κ of solar dark photon from 205.4 kg-day exposure are derived, probing new parameter space with masses (m_{V}) from 10 to 300 eV/c^{2} in direct detection experiments. Considering dark photon as the cosmological dark matter, limits at 90% confidence level with m_{V} from 0.1 to 4.0 keV/c^{2} are set from 449.6 kg-day data, with a minimum of κ=1.3×10^{-15} at m_{V}=200 eV/c^{2}.

Molecular genetic analysis in 21 Chinese families with congenital insensitivity to pain with or without anhidrosis.

BACKGROUND AND PURPOSE: Hereditary sensory and autonomic neuropathies (HSANs) are a group of clinically and genetically heterogeneous neurological disorders characterized by sensory dysfunctions. Here, 21 affected Chinese families are reported, including 19 with congenital insensitivity to pain with anhidrosis (CIPA; namely HSAN IV) and two with congenital insensitivity to pain (CIP; namely HSAN IID) caused by biallelic variations in NTRK1 and SCN9A, respectively, aiming to identify causative variants in these families and compare how different variants in NTRK1 affect the function of tropomyosin receptor kinase A (TrkA). METHODS: Recombinant plasmids harboring the wild-type and six mutant alleles (p.Gln216*, p.Glu584Lys, p.Leu595Arg, p.Pro684Leu, p.Val709Leu and p.Arg765Cys) of NTRK1 cDNA were constructed and transfected into HEK293 cells. RESULTS: The results suggested that the five missense variants only presented a subtle influence on the expression level and glycosylation of TrkA but compromised the receptor phosphorylation. Our findings also suggested that a synonymous variant c.219C>T in NTRK1 may cause aberrant splicing, indicating a potential novel pathogenic mechanism of CIPA. Furthermore, gross deletion of SCN9A was first associated with CIP. CONCLUSIONS: This study identified multiple forms of variants responsible for CIPA/CIP in the Chinese population and might provide new insights into the pathogenesis of CIPA.

[Blood loss in total knee arthroplasty using computer-assisted navigation or 3D-printed patient-specific instruments].

Objective: To compare the perioperative blood loss in patients undergoing a total knee arthroplasty (TKA) across three different techniques: computer-assisted navigation surgery (CAS), patient specific instrumentation (PSI) and conventional instrumentation (CI). Methods: Ninety consecutive patients with severe knee osteoarthritis who underwent unilateral primary TKA in Peking University Third Hospital Orthopedics Department from January 2018 to December 2018 were enrolled in this prospective study. The patients were randomly divided into three groups (30 case in each group): CAS-TKA group, PSI-TKA group and CI-TKA group. The study measured intraoperative blood loss, total blood loss, hidden blood loss, decreases of hemoglobin and hematocrit, and the post-TKA blood transfusions in the three groups. One-way ANOVA was used to detect the differences among the cohorts, and LSD was used for the post-hoc test. Results: The overall intraoperative blood loss of all patients was 6 ml (5~8 ml). The mean total blood loss and hidden blood loss in CAS-TKA group, PSI-TKA group and CI-TKA group was (1 147.0±301.8) and (1 140.1±301.9)ml, (1 044.3±454.1) and (1 038.5±454.0)ml, (1 154.0±483.6) and (1 145.3±482.7)ml, respectively; there was no significant differences among the three groups (F=0.639, 0.616, both P>0.05). There were no patients who received allogeneic blood transfusion. There were no significant differences in decrease of hemoglobin and hematocrit among the three groups neither (both P>0.05). Conclusions: Compared with conventional TKA, CAS and PSI does not increase the total blood loss of TKA. However, they both demonstrate a potential benefit in reducing blood loss of TKA.

[Open hepatectomy versus laparoscopic in the treatment of primary left-sided hepatolithiasis: a propensity, long-term follow-up analysis at a single center].

To compare short-term and long-term efficacy after laparoscopic left hepatectomy(LLR) to open left hepatectomy(OLH) for primary left-sided hepatolithiasis. Methods: Clinical data of 187 patients with left-sided hepatolithiasis and underwent laparoscopically or open left-sided hepatectomy from October 2014 to October 2019 at the Second Affiliated Hospital of Anhui Medical University were retrospectively analyzed in this propensity score matching (PSM) study and were matched in terms of age, sex, body mass index, liver function, ASA score, comorbidities, history of biliary surgery, and smoking history on the ratio of 1∶1.There were 47 cases in each group and the mean age were (54.7±12.3)years old(range:34 to 75 years old) and (53.2±12.6) years old (range: 34 to 75 years old) in open and laparoscopically group respectively. The data of operation time, intraoperative blood loss, postoperative hospital-stay, complication rate, biliary fistula rate, stone clearance rate, and stone recurrence rate were compared. The quantitative data were compared using t-test or rank-sum test. Count data were analyzed with χ(2) test or Fisher test. Results: No significant difference was observed in the clinical characteristics of included 94 patients in this study(all P>0.05).The length of the postoperative hospital-stay after OLH was significantly higher than that in the LLH group((10.8±3.1) days vs.(8.5±2.2)days, t=4.085, P=0.000). LLR significantly decreased the incidence of postoperative biliary fistula compared with the OLH (6.3% vs.21.2%, χ(2)=4.374, P=0.036) and the rates of postoperative complications in the OLH group was significantly higher than that in the LLH group (48.9% vs.27.6%, χ(2)=4.502, P=0.034). Moreover, the stone recurrence rates in the LLH group was significantly lower than that after OLR (4.2% vs. 17.0%, χ(2)=4.029, P=0.045). OLH (95% CI: 1.55 to 10.75, P=0.004) and postoperative complications (95% CI: 1.29 to 9.52, P=0.013) were independent risk factors for prolonged hospital stay. OLH (95% CI: 1.428 to 44.080, P=0.018) and residual stones (95% CI: 1.580 to 62.379, P=0.014) were independent risk factors for the occurrence of postoperative biliary fistula. Biliary fistula (95% CI: 1.078 to 24.517, P=0.040) was an independent risk factor for the recurrence of stones. Conclusion: Compared with OLH, LLH is safe and effective for the treatment of the primary left-sided hepatolithiasis with the clinical benefits of shorter hospital stay, fewer morbidity and biliary fistula occurrence, and lower stone recurrence rates.

Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study.

PURPOSE: HER2-targeted therapies have substantially improved the outcome of patients with breast cancer, however, they can be associated with cardiac toxicity. Guidelines recommend holding HER2-targeted therapies until resolution of cardiac dysfunction. SAFE-HEaRt is the first trial that prospectively tests whether these therapies can be safely administered without interruptions in patients with cardiac dysfunction. METHODS: Patients with stage I-IV HER2-positive breast cancer candidates for trastuzumab, pertuzumab or ado-trastuzumab emtansine (TDM-1), with left ventricular ejection fraction (LVEF) 40-49% and no symptoms of heart failure (HF) were enrolled. All patients underwent cardiology visits, serial echocardiograms and received beta blockers and ACE inhibitors unless contraindicated. The primary endpoint was completion of the planned HER2-targeted therapies without developing either a cardiac event (CE) defined as HF, myocardial infarction, arrhythmia or cardiac death or significant asymptomatic worsening of LVEF. The study was considered successful if planned oncology therapy completion rate was at least 30%. RESULTS: Of 31 enrolled patients, 30 were evaluable. Fifteen patients were treated with trastuzumab, 14 with trastuzumab and pertuzumab, and 2 with TDM-1. Mean LVEF was 45% at baseline and 46% at the end of treatment. Twenty-seven patients (90%) completed the planned HER2-targeted therapies. Two patients experienced a CE and 1 had an asymptomatic worsening of LVEF to ≤ 35%. CONCLUSION: This study provides safety data of HER2-targeted therapies in patients with breast cancer and reduced LVEF while receiving cardioprotective medications and close cardiac monitoring. Our results demonstrate the importance of collaboration between cardiology and oncology providers to allow for delivery of optimal oncologic care to this unique population.

Mitochondrial DNA mutation m.3243A>G is associated with altered mitochondrial function in peripheral blood mononuclear cells, with heteroplasmy levels and with clinical phenotypes.

AIMS: To investigate the associations among heteroplasmy levels (i.e. the proportions of mutant and wild-type mitochondrial DNA in the same cell), mitochondrial function and clinical severity of the m.3243A>G mutation. METHODS: A total of 17 participants carrying the m.3243A>G mutation and 17 sex- and age-matched healthy controls were included in this study. Heteroplasmy levels of the m.3243A>G mutation in leukocytes, saliva and urine sediment were determined by pyrosequencing. The clinical evaluation included endocrinological, audiological and ophthalmological examinations. Mitochondrial function was determined in peripheral blood mononuclear cells isolated from participants. RESULTS: Heteroplasmy levels in urine sediment were higher than those in leukocytes and saliva. Reduced levels of adenosine triphosphate and mitochondrial membrane potential, and increased reactive oxygen species production were observed in mutant peripheral blood mononuclear cells (all P < 0.05). Linear regression analysis indicated that higher heteroplasmy levels in peripheral blood leukocytes were associated with increased levels of glycated albumin and HbA1c , and decreased total hip bone mineral density T-score after adjustment for age and sex (all P < 0.05). Furthermore, mitochondrial membrane potential was independently associated with bone mineral density T-score at the femoral neck (P < 0.05). CONCLUSIONS: Heteroplasmy levels in peripheral blood leukocytes and mitochondrial membrane potential in peripheral blood mononuclear cells were closely associated with clinical manifestations and were valuable for evaluation of the clinical severity of the m.3243A>G mutation.

Lymphovascular invasion as a poor prognostic indicator in thoracic esophageal carcinoma: a systematic review and meta-analysis.

The ability to further stratify patients with esophageal carcinoma (EC) in the same stage into high-risk patients by the presence of lymphovascular invasion (LVI) may permit refinement of multi-modality therapy. However, the role of LVI in the prognosis of EC is not definite. A meta-analysis was conducted to investigate the relationship between LVI and EC prognosis. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies on the association between LVI and prognosis of EC. Only studies with patient survival data related to LVI were included. The effect size for this analysis was the hazard ratio (HR) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS). Thirty-five studies with 9876 patients were included according to the defined inclusion and exclusion criteria. LVI was a poor indicator for the OS (HR = 1.64, 95% CI: 1.44-1.87, P < 0.001) and RFS (HR = 1.79, 95% CI: 1.38-2.34, P < 0.001). However, the heterogeneity was medium in OS (I2 = 61.2%, P < 0.001) and extreme in RFS (I2 = 77.5%, P < 0.001). In subgroup analysis, heterogeneity was originated from the staining method and proportion of early disease (stage (I + II)). We concluded that LVI was a poor prognostic indicator in patients with EC, especially in those studies with the IHC staining method and a high proportion of early disease (stage (I + II)).

Comparative transcriptome analyses of adzuki bean weevil (Callosobruchus chinensis) response to hypoxia and hypoxia/hypercapnia.

Stored product insects show high adaption to hypoxia and hypercapnia, but the underlying mechanism is still unclear. Herein, a comparative transcriptome on 4th adzuki bean weevil (Callosobruchus chinensis) instar larvae was studied to clarify the response mechanisms to hypoxia (HA) and hypoxia/hypercapnia (HHA) using NextSeq500 RNA-Seq. Transcript profiling showed a significant difference in HA or HHA exposure both quantitatively and qualitatively. Compared with control, 631 and 253 genes were significantly changed in HHA and HA, respectively. Comparing HHA with HA, 1135 differentially expressed genes (DEGs) were identified. The addition of hypercapnia made a complex alteration on the hypoxia response of bean weevil transcriptome, carbohydrate, energy, lipid and amino acid metabolism were the most highly enriched pathways for genes significantly changed. In addition, some biological processes that were not significantly enriched but important were also discussed, such as immune system and signal transduction. Most of the DEGs related to metabolism both in HHA and HA were up-regulated, while the DEGs related to the immune system, stress response or signal transduction were significantly down-regulated or suppressed. This research reveals a comparatively full-scale result in adzuki bean weevil hypoxia and hypoxia/hypercapnia tolerance mechanism at transcription level, which might provide new insights into the genomic research of this species.