[Endometriosis-related recurrent unilateral hemorrhagic pleural effusion: a case report].

Hemorrhagic pleural effusion (PE) is common in clinical practice. According to the guidelines, the etiological diagnosis of PE should focus on the identification of common diseases. In most cases, the etiology of PE can be determined by clinical history, physical examination, laboratory and imaging examinations, and pleural biopsy or video-assisted thoracic surgery (VAST). We reported a rare case of a 32-year-old woman with recurrent unilateral hemorrhagic pleural effusion (highly correlated with menstrual cycle) and chest pain that was diagnosed as thoracic endometriosis syndrome (TES) by pathological biopsy and immunohistochemistry. Later she underwent surgery combined with hormone therapy. During the follow-up, the right PE decreased, and she had no chest pain. Therefore, women of reproductive age with regular unilateral bloody pleural effusions should be alert to TES.

[Early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency].

Objective: To examine the early to mid-term clinical outcomes of aortic valve repair in patients with bicuspid aortic insufficiency. Methods: This is a retrospective cohort study. The clinical data of 124 patients with BAV insufficiency who underwent aortic valve repair from January 2017 to June 2023 in the Department of Cardiovascular Surgery at Fuwai Hospital were analyzed retrospectively. There were 117 males and 7 females with an age of (38.1±12.7) years (range: 14 to 65 years). Depending on whether the aortic sinus was replaced or not, surgical approaches were divided into valve sparing root replacement (reimplantation, remodeling, modified remodeling) and isolated aortic valve repair (annuloplasty, isolated aortic valve leaflet repair). Perioperative and follow-up data were collected. Kaplan-Meier method was used to plot the curves of survival rate, free recurrence rate of massive aortic valve insufficiency and free re-operation rate, and Log-rank test was used for comparison between groups. Results: Among the surgeries, there were 47 cases of reimplantation, 8 cases of remodeling, 8 cases of modified remodeling, 48 cases of aortic annuloplasty (external annuloplasty in 22 cases, CV-0 annuloplasty in 26 cases), and 13 cases of isolated leaflet repair. Leaflet plication was the most used leaflet repair technique, used in 103 patients. The cardiopulmonary bypass time was (133.7±56.9) minutes (range: 48 to 461 minutes), and aortic cross-clamp time was (103.8±47.8) minutes (range: 25 to 306 minutes), with no surgical mortality. All patients underwent outpatient or telephone follow-up. The cumulative follow-up time was 340.3 person-years and the mean follow-up time was (M (IQR)) 34.0 (25.5) months (range: 3 to 76 months). The 5-year survival rate was 98.4%, the 5-year freedom from significant insufficiency rate was 93.4% and the 5-year freedom from aortic valve reoperation rate was 95.6%. The subgroup analysis revealed a significantly better freedom from the significant insufficiency rate in the aortic valve annular reduction group compared to the non-reduction group (P<0.01). Conclusions: Aortic valve repair in patients with bicuspid aortic insufficiency could obtain steady early to mid-term outcomes. Aortic annuloplasty can reduce the risk of recurrent aortic valve insufficiency in patients undergoing aortic repair.

Search for Boosted Dark Matter in COSINE-100.

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

Acute exacerbation of chronic obstructive pulmonary disease in a slaughterhouse.

We describe the case of a 52-year-old male who presented with two episodes of acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) during work, while suspending live chickens for slaughter. The patient was exposed to high levels of bioaerosols, including endotoxins and microorganisms. Endotoxins can induce bronchoconstriction and airway inflammation, and COPD patients are more vulnerable to airway infections caused by microorganisms inhaled with bioaerosols. This study suggests that a high level of bioaerosols may induce airway infections, resulting in acute exacerbations of COPD.

[Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia].

OBJECTIVE: To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer. METHODS: Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve. RESULTS: A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration. CONCLUSION: It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

[Clinical characteristics and outcome of malignant hydronephrosis associated with colorectal carcinoma].

Objective: To explore the clinical characteristics and outcome of hydronephrosis associated with advanced or metastatic colorectal carcinoma. Methods: Clinical data of 311 patients with locally advanced or metastatic colorectal carcinoma between June 2017 and March 2020 in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital were retrospectively collected. Thirty-nine patients with hydronephrosis diagnosed by CT scan were analyzed. Kaplan-Meier method was used for survival analysis, Log rank method was used for comparison of survival between the two groups with or without hydronephrosis, and univariate and multivariate analyses was performed by Cox proportional risk regression model. Results: The incidence rate of malignant hydronephrosis associated with metastatic colorectal carcinoma was 12.5% (39/311), 26 were male, and 13 were female. The median age was 43 years (23-74 years). Among the 39 patients, 29 had unilateral hydronephrosis and 10 had bilateral hydronephrosis. Eleven patients with hydronephrosis at the initiate diagnosis, 28 patients with hydronephrosis at relapse or advanced course, and the median time to hydronephrosis was 17 months (4-62 months). The disease control rate (DCR, 77.8% and 84.6%, respectively) and progression free survival (PFS were 6 and 7 months) were not significantly different between patients with hydronephrosis and without hydronephrosis received the first-line chemotherapy (P>0.05). The median overall survival (OS) after presence of hydronephrosis was 26 months (95%CI: 8.3, 43.7). Multivariate analyses showed that the blood vessel invasion (LVSI) was an independent risk factor for OS (P<0.05). Conclusions: Malignant hydronephrosis had no effect on the efficacy of the first-line chemotherapy and PFS of patients with colorectal carcinoma received the first-line chemotherapy. LVSI was the independent prognostic factor for OS of patients with malignant hydronephrosis.

[Changes in platelet related parameters in obese patients after sleeve gastrectomy].

To compare changes in platelet related parameters in obese patients before and after sleeve gastrectomy (SG), we retrospectively analyzed the clinical data of 31 obese patients who underwent SG in Peking Union Medical College Hospital from December 2012 to September 2020. Results showed that compared with those before surgery, platelet count (PLT) decreased significantly at 2-12 weeks of follow-up (P=0.009), while platelet distribution width (PDW), mean platelet volume (MPV), and large platelet ratio (P-LCR) increased significantly at the same periods of follow-up after operation (P<0.001). However, the levels of PDW, MPV, and P-LCR began to decrease at 16-55 weeks when compared with those at 2-12 weeks of follow-up (P<0.01). PLT was positively correlated with white blood cells and neutrophils at 2-12 weeks of follow-up and positively correlated with high sensitivity C-reactive protein at 16-55 weeks of follow-up after operation (P<0.05).

[Adrenal cavernous hemangioma: A case report and literature review].

A 57-year-old male patient was referred to our department with complaints of his right adrenal gland occupancy and hypertension about 6 months. When admitted to the hospital, the blood pressure was about 160/100 mmHg, and the heart rate was 110 beats/min. He was no obvious obesity, acne, abnormal mood, without weakness of limbs, acral numbness, palpitation and headache. He presented with type 2 diabetes for more than 3 years, with oral administration of metformin enteric coated tablets and subcutaneous injection of insulin glargine to control blood glucose, and satisfied with blood glucose control. Enhanced CT showed that: the right adrenal gland showed a kind of oval isodense, slightly hypodense shadow, the edge was clear, lobular change, the size was about 5.8 cm×5.4 cm, uneven density, there were nodular and strip calcification, round lipid containing area and strip low density area, and the CT value of solid part was about 34 HU. Enhanced scan showed heterogeneous nodular enhancement in the solid part of the right adrenal gland, nodular enhancement could be seen inside. The CT values of solid part in arterial phase, venous phase and delayed phase were 45 HU, 50 HU and 81 HU, respectively. Considering from the right adrenal gland, cortical cancer was more likely. No obvious abnormality was found in his endocrine examination. After adequate preoperative preparation, retroperitoneal laparoscopic adrenalectomy was performed under general anesthesia. During the operation, the 6 cm adrenal tumor was closely related to the inferior vena cava and liver, and after careful separation, the tumor was completely removed and normal adrenal tissue was preserved. The operation lasted 180 min and the blood loss was 100 mL, and the blood pressure was stable during and after the operation. There was no obvious complication. The results of pathological examinations were as follows: the size of the tumor was 7.5 cm×6.0 cm×3.5 cm, soft, with intact capsule and grayish-red cystic in section. Pathological diagnosis: (right adrenal gland) cavernous hemangioma, secondary intravascular thrombosis, old hemorrhagic infarction with calcification and ossification. After 6 months of observation, no obvious complications and tumor recurrence were found. In summary, cavernous hemangioma of adrenal gland is a rare histopathological change. Its essence is a malformed vascular mass. Blood retention is the cause of thrombosis and calcification in malformed vessels. The imaging findings were inhomogeneous enhancement of soft tissue masses, and the adrenal function examination showed no obvious abnormalities. Retroperitoneal laparoscopic surgery is feasible after adequate preoperative preparation. It is difficult to diagnose the disease preoperatively and needs to be confirmed by postoperative pathology.

[Veracity of using a visual chart with a testing distance of 2.5 meters for measurement of distance visual acuity in teenagers].

Objective: To compare the results of visual acuity testing for teenagers with visual acuity charts designed at 2.5-meter and 5-meter distances, and to investigate the accuracy of the 2.5-meter visual acuity chart. Methods: It was a self-control study. A total of 227 teenagers (454 eyes) with ametropia who came to the ophthalmic clinic of Peking Union Medical College Hospital from March 2019 to September 2019 were included. There were 123 males and 104 females aged (11.74±3.26) years. The vision examiners were trained in the same testing environment and passed the consistency test. Distance visual acuity of all participants was tested with charts designed at 2.5 meters and 5 meters in a 10-minute interval. According to the age (7-9, 10-12, 13-15 and 16-18 years old) and visual acuity (1.00-0.52, 0.40-0.30 and 0.22-0.10), the results of two kinds of visual acuity charts were compared. The testing order of the two visual charts was randomly determined. The visual acuity results were converted into logMAR values and compared. Paried t-student test was used to compare the difference between two charts, and Pearson correlation test was used to explore the correlation between the results of two charts. Results: The visual acuity of the right eye was 0.37±0.24 (logMAR) at 2.5 meters and 0.50±0.26 (logMAR) at 5 meters. The distance visual acuity measured with the 2.5-meter visual acuity chart was better (t=16.19, P<0.01). The visual acuity of the left eye was 0.36±0.23 (logMAR) at 2.5 meters and 0.45±0.23 (logMAR) at 5 meters (t=11.71, P<0.01). The differences between two charts were larger among teenagers with lower visual acuity (r=0.387,P<0.01). Conclusion: Under the same test conditions, the distance visual acuity measured with a 2.5-meter chart was significantly better than a 5-meter chart. The visual acuity chart designed at 2.5 meters was not an appropriate tool to measure distance vision in adolescents. (Chin J Ophthalmol, 2021, 57: 122-125).

The histone deacetylase inhibitor chidamide induces intermittent viraemia in HIV-infected patients on suppressive antiretroviral therapy.

OBJECTIVES: To evaluate the safety and efficacy of chidamide to reverse HIV-1 latency in vivo and to compare the effects of four clinically tested histone deacetylase (HDAC) inhibitors on non-histone proteins in vitro. METHODS: Participants received chidamide orally at 10 mg twice weekly for 4 weeks while maintaining baseline antiretroviral therapy. The primary outcome was plasma viral rebound during chidamide dosing and the secondary outcomes were safety, pharmacokinetic and pharmacodynamic profiles, changes in cell-associated HIV-1 RNA and HIV-1 DNA, and immune parameters. Western blotting was used to compare the in vitro effects of the four HDAC inhibitors on HSP90, NF-κB and AP-1. RESULTS: Seven aviraemic participants completed eight oral doses of chidamide, and only grade 1 adverse events were observed. Cyclic increases in histone acetylation were also detected. All participants showed robust and repeated plasma viral rebound (peak viraemia 147-3850 copies/mL), as well as increased cell-associated HIV-1 RNA, during chidamide treatment. Furthermore, we identified an enhanced HIV-1-specific cellular immune response and a modest 37.7% (95% CI: 12.7-62.8%, P = 0.028) reduction in cell-associated HIV-1 DNA. Compared with the other three HDAC inhibitors, chidamide had minimal cytotoxicity in vitro at clinically relevant concentrations and showed mechanistically superior effects on non-histone proteins, including HSP90, NF-κB and AP-1. CONCLUSIONS: Chidamide safely and vigorously disrupts HIV-1 latency in vivo, which makes it a promising latency-reversing agent.

Functional divergence of white genes in Henosepilachna vigintioctopunctata revealed by RNA interference.

Henosepilachna vigintioctopunctata is a serious pest of Solanaceae and Cucurbitaceae in many Asian countries. RNA interference (RNAi) can effectively reduce transcript abundance in this beetle, offering opportunities to explore the biological function of specific genes. The white gene encodes a half-type ATP-binding cassette transporter that plays an essential role in tryptophan, guanine and uric acid transport across membranes. Mutations that disrupt the function of white are known to cause eye pigmentation phenotypes in many insect species. Here, we found evidence for five white gene paralogues present in H. vigintioctopunctata transcriptome datasets sequenced from a range of developmental stages. We individually knocked down each of the five white genes through the injection of corresponding double-stranded RNAs (dsRNAs) to the fourth-instar larvae to determine whether functional divergence has occurred. We found that injecting 1 µg dswhite3 caused compound eye colour of pupae and adults to develop as red/brown and brown, respectively, compared with black eyes in control beetles. Injection of 2 µg dswhite3 increased RNAi efficacy and produced a clearer eye colour phenotype. At both doses, the ocular diaphragm (a ring of black pigment surrounding each eye) did not change in the white3 RNAi hypomorphs. Moreover, our data revealed that injection of dswhite2 at the fourth-instar larval stage impaired the climbing ability of both male and female adults. Our results confirmed, for the first time, functional divergence of duplicated white genes in an insect species.

Particle-Hole Symmetry and the Fractional Quantum Hall Effect in the Lowest Landau Level.

We report on detailed experimental studies of a high-quality heterojunction insulated-gate field-effect transistor (HIGFET) to probe the particle-hole symmetry of the fractional quantum Hall effect (FQHE) states about half-filling in the lowest Landau level. The HIGFET is specially designed to vary the density of a two-dimensional electronic system under constant magnetic fields. We find in our constant magnetic field, variable density measurements that the sequence of FQHE states at filling factors ν=1/3,2/5,3/7… and its particle-hole conjugate states at filling factors 1-ν=2/3,3/5,4/7… have a very similar energy gap. Moreover, a reflection symmetry can be established in the magnetoconductivities between the ν and 1-ν states about half-filling. Our results demonstrate that the FQHE states in the lowest Landau level are manifestly particle-hole symmetric.

Dose and time effects of solar-simulated ultraviolet radiation on the in vivo human skin transcriptome.

BACKGROUND: Terrestrial ultraviolet (UV) radiation causes erythema, oxidative stress, DNA mutations and skin cancer. Skin can adapt to these adverse effects by DNA repair, apoptosis, keratinization and tanning. OBJECTIVES: To investigate the transcriptional response to fluorescent solar-simulated radiation (FSSR) in sun-sensitive human skin in vivo. METHODS: Seven healthy male volunteers were exposed to 0, 3 and 6 standard erythemal doses (SED). Skin biopsies were taken at 6 h and 24 h after exposure. Gene and microRNA expression were quantified with next generation sequencing. A set of candidate genes was validated by quantitative polymerase chain reaction (qPCR); and wavelength dependence was examined in other volunteers through microarrays. RESULTS: The number of differentially expressed genes increased with FSSR dose and decreased between 6 and 24 h. Six hours after 6 SED, 4071 genes were differentially expressed, but only 16 genes were affected at 24 h after 3 SED. Genes for apoptosis and keratinization were prominent at 6 h, whereas inflammation and immunoregulation genes were predominant at 24 h. Validation by qPCR confirmed the altered expression of nine genes detected under all conditions; genes related to DNA repair and apoptosis; immunity and inflammation; pigmentation; and vitamin D synthesis. In general, candidate genes also responded to UVA1 (340-400 nm) and/or UVB (300 nm), but with variations in wavelength dependence and peak expression time. Only four microRNAs were differentially expressed by FSSR. CONCLUSIONS: The UV radiation doses of this acute study are readily achieved daily during holidays in the sun, suggesting that the skin transcriptional profile of 'typical' holiday makers is markedly deregulated. What's already known about this topic? The skin's transcriptional profile underpins its adverse (i.e. inflammation) and adaptive molecular, cellular and clinical responses (i.e. tanning, hyperkeratosis) to solar ultraviolet radiation. Few studies have assessed microRNA and gene expression in vivo in humans, and there is a lack of information on dose, time and waveband effects. What does this study add? Acute doses of fluorescent solar-simulated radiation (FSSR), of similar magnitude to those received daily in holiday situations, markedly altered the skin's transcriptional profiles. The number of differentially expressed genes was FSSR-dose-dependent, reached a peak at 6 h and returned to baseline at 24 h. The initial transcriptional response involved apoptosis and keratinization, followed by inflammation and immune modulation. In these conditions, microRNA expression was less affected than gene expression.

A longitudinal study on α-synuclein in plasma neuronal exosomes as a biomarker for Parkinson's disease development and progression.

BACKGROUND AND PURPOSE: The identification of reliable diagnostic and prognostic biomarkers for Parkinson's disease (PD) is urgently needed. Here, we explored the potential use of α-synuclein (α-syn) in plasma neuronal exosomes as a biomarker for early PD diagnosis and disease progression. METHODS: This study included both cross-sectional and longitudinal designs. The subjects included 36 patients with early-stage PD, 17 patients with advanced PD, 20 patients with idiopathic rapid eye movement sleep behavior disorder and 21 healthy controls (HCs). α-syn levels were measured by electrochemiluminescence immunoassay. A subgroup of patients with early-stage PD (n = 18) participated in a follow-up examination with repeated blood collection and clinical assessments after an average of 22 months. RESULTS: The α-syn levels in plasma neuronal exosomes were significantly higher in patients with early-stage PD compared with HCs (P = 0.007). Differences in α-syn levels between patients with idiopathic rapid eye movement sleep behavior disorder and HCs did not reach statistical significance (P = 0.08). In addition, Spearman correlation analysis revealed that neuronal exosomal α-syn concentrations were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale III/(I + II + III) scores, Non-Motor Symptom Questionnaire scores and Sniffin' Sticks 16-item test scores of patients with PD (P < 0.05). After a mean follow-up of 22 months in patients with early-stage PD, a Cox regression analysis adjusted for age and gender showed that longitudinally increased α-syn rather than baseline α-syn levels were associated with higher risk for motor symptom progression in PD (P = 0.039). CONCLUSIONS: Our results suggested that α-syn in plasma neuronal exosomes may serve as a biomarker to aid early diagnosis of PD and also as a prognostic marker for PD progression.

[Comparison of short-term clinical outcome between laparoscopic distal pancreatectomy and open distal pancreatectomy].

Objective: To compare the short-term clinical effect between laparoscopic distal pancreatectomy (LDP) and open distal pancreatectomy (ODP). Methods: We performed a retrospective study on 161 patients who underwent pancreatectomy between September 2017 to December 2018 in the Department of Pancreatic and Gastric Surgery, Cancer Hospital of Chinese Academy of Medical Sciences. According to the mode of operation, the patients were divided into the LDP group (n=43) and the ODP group (n=118). To compare the short-term clinical effect and safety between the LDP group and the ODP group, the preoperative clinical data, intraoperative related index, postoperative complication, postoperative recovery index, preoperative and postoperative inflammatory index were analyzed. Results: The preoperative clinical characteristics between the LDP group and the ODP group were not statistically different (P>0.05). The intraoperative blood loss in LDP group was (194.19±241.83) ml, significantly less than (315.17±295.94) ml in ODP group (P<0.05), and the postoperative exhaust time in LDP group was (3.00±0.72) days, significantly shorter than (4.05±0.97) days in OPD group (P<0.001). The time to get out of bed in LDP group was (3.14±1.01) days, significantly shorter than (3.55±1.05) days in OPD group (P<0.05). The postoperative eating time in LDP group was (3.88±1.61) days, significantly shorter than (5.11±1.56) days in ODP group (P<0.001). The time of the drainage tube removal in LDP group was (8.44±1.93) days, significantly shorter than (9.82±3.70) days in ODP group (P<0.05). The postoperative hospital stay in LDP group was (9.65±3.57) days, significantly shorter than (11.99±6.57) days in ODP group (P<0.05). The mean operation time in LDP group was (168.65±55.45) min, shorter than (171.23±65.61) min in ODP group, but without significant difference (P>0.05). The incidences of non-pancreatic fistula-related complications in LDP group and ODP group were 16.3% and 11.0%, respectively, without statistical significance (P>0.05). The incidences of pancreatic fistula in LDP group and ODP group were 16.3% and 19.5%, respectively, without statistical significance (P>0.05). The total incidences of complications in LDP group and ODP group were 32.6% and 30.5%, respectively, without statistical significance (P>0.05). The preoperative and postoperative inflammatory indexes between these two groups were not statistically different (P>0.05). Conclusions: Compared with ODP, LDP has the advantages of less intraoperative blood loss, faster postoperative recovery, shorter postoperative hospital stays, without increased postoperative complications and prolonged operation time. LDP is a safe and feasible operation method, and its short-term clinical effect is better than that of ODP.

[Clinical characteristics and influencing factors of patients with novel coronavirus pneumonia combined with liver injury in Shaanxi region].

Objective: To understand the clinical characteristics, change of liver function, influencing factors and prognosis in hospitalized patients with coronavirus disease-19 (COVID-19) combined with liver injury. Methods: The general conditions, biochemical indicators of liver, blood clotting mechanism, routine blood test, UGT1A1 * 28 gene polymorphism and other data of 40 cases with COVID-19 admitted to the isolation ward of Tangdu Hospital were retrospectively analyzed. The clinical characteristics, influencing factors and prognosis of liver injury in patients with liver injury group and those with normal liver function group were compared. The mean of two samples in univariate analysis was compared by t-test and analysis of variance. The counting data was measured by χ(2) tests. The non-normal distribution measurement data were described by the median, and the non-parametric test was used. Statistically significant influencing factors were used as the independent variables in univariate analysis. Multiple logistic regression analysis was used to analyze the main influencing factors of liver injury. Results: Of the 40 cases, 25 were male (62.5%) and 15 were female (37.5%), aged 22 to 83 (53.87 ± 15.84) years. Liver injury was occurred in 22 cases (55%) during the course of the disease. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level was initially increased (4.4 to 3.5 times of the normal value) along with decrease of albumin in the second week, and the difference was statistically significant (P < 0.001). Ten cases (43.5%) had highest abnormal total blood bilirubin (54.1 µmol/ L). There was no correlation between the increase in transaminase and the increase in total blood bilirubin (R = -0.006, P = 0.972). Three cases had prothrombin activity (PTA) of ≤50%, 10 cases had elevated FDP, and 13 cases had elevated D-dimer, all of whom were severe or critically ill. Liver function injury was more likely to occur in patients who used many types of drugs and large amounts of hormones (P = 0.002, P = 0.031), and there was no correlation with the TA6TA7 mutation in the UGT1A1 * 28 gene locus. Multiple regression analysis showed that the occurrence of liver injury was only related to critical illness. The liver function of all patients had recovered within one week after conventional liver protection treatment. Conclusion: COVID-19 combined with liver function injury may be due to the slight elevation of transaminase, mostly around the second week of the disease course. Severe patients have a higher proportion of liver injury, and critical type is an independent risk factor for liver injury.

[Comparison of clinical features between patients with acute-on-chronic liver failure and decompensated liver cirrhosis combined with acute kidney injury].

Objective: To compare the clinical features between patients with acute-on-chronic liver failure (ACLF) and decompensated liver cirrhosis (DC) combined with acute kidney injury (AKI). Methods: Demographic data, clinical examination results, diagnosis and treatment information of ACLF and DC patients were collected retrospectively. Clinical characteristics of ACLF combined with AKI and DC combined with AKI and their impact on the 90-day mortality risk were compared. Results: The clinical characteristics of patients with ACLF-AKI and DC-AKI were compared. The results showed that the leukocyte count, absolute neutrophil count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil) of ACLF-AKI patients were higher than those of DC-AKI patients, while prothrombin activity (PTA), and albumin were lower than those of DC-AKI patients, and the difference was statistically significant (P < 0.05). The co-infection rate in patients with ACLF-AKI was significantly higher than that of DC-AKI group (96.9% vs. 39.5%) (P < 0.05), and during the diagnosis of AKI, the median value of serum creatinine in ACLF patients was 147 µmol / L (IQR: 122-189), while that in DC group was 123.5 µmol / L (IQR: 103.8-155.5), and the difference between the two groups was statistically significant (P < 0.05). According to the HRS-AKI diagnostic criteria for liver cirrhosis, 44 (68.8%) cases of ACLF-AKI met the diagnosis of HRS -AKI, which was significantly higher than the proportion of 18 (47.4%) cases of DC-AKI (P < 0.05). Four (10.5%) cases of DC-AKI had died or underwent liver transplantation within 30 days and eight (21.1%) cases had died or underwent liver transplantation within 90 days, while 22 (34.4%) cases of ACLF-AKI patients had died or underwent liver transplantation within 30 days and 35 (54.7%) cases had died or underwent liver transplantation within 90 days, and χ (2) values was 7.140 and 11.062, respectively (P < 0.05). The results of multivariate regression analysis suggested that the independent risk factors that affect the 90-days mortality rate of DC patients were hepatic encephalopathy, gastrointestinal bleeding, and TBil, while the independent risk factors affecting the 90-days death risk of ACLF patients included AKI, PTA and TBil. Conclusion: Compared with DC-AKI patients, ACLF-AKI patients have a higher proportion of infection rate, higher serum creatinine level when diagnosed AKI, and faster disease progression, leading to a greater risk of death.

Epigenomic promoter alterations predict for benefit from immune checkpoint inhibition in metastatic gastric cancer.

BACKGROUND: Utilization of alternative transcription start sites through alterations in epigenetic promoter regions causes reduced expression of immunogenic N-terminal peptides, which may facilitate immune evasion in early gastric cancer. We hypothesized that tumors with high alternate promoter utilization would be resistant to immune checkpoint inhibition in metastatic gastric cancer. PATIENTS AND METHODS: Two cohorts of patients with metastatic gastric cancer treated with immunotherapy were analyzed. The first cohort (N = 24) included patients treated with either nivolumab or pembrolizumab. Alternate promoter utilization was measured using the NanoString® (NanoString Technologies, Seattle, WA, USA) platform on archival tissue samples. The second cohort was a phase II clinical trial of patients uniformly treated with pembrolizumab (N = 37). Fresh tumor biopsies were obtained, and transcriptomic analysis was carried out on RNAseq data. Alternate promoter utilization was correlated to T-cell cytolytic activity, objective response rate and survival. RESULTS: In the first cohort 8 of 24 (33%) tumors were identified to have high alternate promoter utilization (APhigh), and this was used to define the APhigh tertile of the second cohort (13 APhigh of 37). APhigh tumors exhibited decreased markers of T-cell cytolytic activity and lower response rates (8% versus 42%, P = 0.03). Median progression-free survival was lower in the APhigh group (55 versus 180 days, P = 0.0076). In multivariate analysis, alternative promoter utilization was an independent predictor of immunotherapy survival [hazard ratio 0.29, 95% confidence interval 0.099-0.85, P = 0.024). Analyzing tumoral evolution through paired pre-treatment and post-treatment biopsies, we observed consistent shifts in alternative promoter utilization rate associated with clinical response. CONCLUSION: A substantial proportion of metastatic gastric cancers utilize alternate promoters as a mechanism of immune evasion, and these tumors may be resistant to anti-PD1 immune checkpoint inhibition. Alternate promoter utilization is thus a potential mechanism of resistance to immune checkpoint inhibition, and a novel predictive biomarker for immunotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT#02589496.

Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4).

BACKGROUND: Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated. PATIENTS AND METHODS: Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. RESULTS: Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively. CONCLUSION: Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX. CLINICALTRIALS.GOV ID: NCT02746796.