Effect of an artificial intelligence-assisted system on endoscopic diagnosis of superficial oesophageal squamous cell carcinoma and precancerous lesions: a multicentre, tandem, double-blind, randomised controlled trial.

BACKGROUND: Despite the usefulness of white light endoscopy (WLE) and non-magnified narrow-band imaging (NBI) for screening for superficial oesophageal squamous cell carcinoma and precancerous lesions, these lesions might be missed due to their subtle features and interpretation variations among endoscopists. Our team has developed an artificial intelligence (AI) system to detect superficial oesophageal squamous cell carcinoma and precancerous lesions using WLE and non-magnified NBI. We aimed to evaluate the auxiliary diagnostic performance of the AI system in a real clinical setting. METHODS: We did a multicentre, tandem, double-blind, randomised controlled trial at 12 hospitals in China. Eligible patients were aged 18 years or older and underwent sedated upper gastrointestinal endoscopy for screening, investigation of gastrointestinal symptoms, or surveillance. Patients were randomly assigned (1:1) to either the AI-first group or the routine-first group using a computerised random number generator. Patients, pathologists, and statistical analysts were masked to group assignment, whereas endoscopists and research assistants were not. The same endoscopist at each centre did tandem upper gastrointestinal endoscopy for each eligible patient on the same day. In the AI-first group, the endoscopist did the first examination with the assistance of the AI system and the second examination without it. In the routine-first group, the order of examinations was reversed. The primary outcome was the miss rate of superficial oesophageal squamous cell carcinoma and precancerous lesions, calculated on a per-lesion and per-patient basis. All analyses were done on a per-protocol basis. This trial is registered with the Chinese Clinical Trial Registry (ChiCTR2100052116) and is completed. FINDINGS: Between Oct 19, 2021, and June 8, 2022, 5934 patients were randomly assigned to the AI-first group and 5912 to the routine-first group, of whom 5865 and 5850 were eligible for analysis. Per-lesion miss rates were 1·7% (2/118; 95% CI 0·0-4·0) in the AI-first group versus 6·7% (6/90; 1·5-11·8) in the routine-first group (risk ratio 0·25, 95% CI 0·06-1·08; p=0·079). Per-patient miss rates were 1·9% (2/106; 0·0-4·5) in AI-first group versus 5·1% (4/79; 0·2-9·9) in the routine-first group (0·37, 0·08-1·71; p=0·40). Bleeding after biopsy of oesophageal lesions was observed in 13 (0·2%) patients in the AI-first group and 11 (0·2%) patients in the routine-first group. No serious adverse events were reported by patients in either group. INTERPRETATION: The observed effect of AI-assisted endoscopy on the per-lesion and per-patient miss rates of superficial oesophageal squamous cell carcinoma and precancerous lesions under WLE and non-magnified NBI was consistent with substantial benefit through to a neutral or small negative effect. The effectiveness and cost-benefit of this AI system in real-world clinical settings remain to be further assessed. FUNDING: National Natural Science Foundation of China, 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University, and Chengdu Science and Technology Project. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Correlation of serum albumin level on postoperative day 2 with hospital length of stay in patients undergoing emergency surgery for perforated peptic ulcer.

BACKGROUND: Perforated peptic ulcer (PPU) is a common emergency surgical condition and a significant cause of morbidity and mortality worldwide. While advances in surgical techniques have improved outcomes for patients with PPU, many factors still affect postoperative hospital stay and overall prognosis. One potential factor is the serum albumin (SA) level, a widely utilized marker of nutritional status that has been associated with length of stay and complications in various surgical procedures. AIM: To clarify the correlation of SA level on postoperative day 2 with hospital length of stay (HLOS) in patients undergoing emergency surgery for perforated peptic ulcer (PPU). METHODS: We retrospectively collected and analyzed clinical baseline data, including blood routine and SA levels, of patients who underwent emergency PPU surgery and postoperative treatment at the Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University between December 2012 and September 2021. Patients were grouped according to HLOS with 7 d as the cut-off value, and relevant indicators were analyzed using SPSS 26.0. RESULTS: Of the 37 patients undergoing emergency surgery for PPU referred to our department, 33 had gastric and 4 had duodenal ulcer perforation. The median HLOS was 10 d. There were 8 patients in the ≤ 7-d group (median HLOS: 7 d) and 29 patients in the > 7-d group (median HLOS: 10 d). The ≤ 7-d group had markedly higher SA on postoperative day 2 than the > 7-d group (37.7 g/L vs 32.6g/L; P < 0.05). The SA level on postoperative day 2 was a protective factor for patients with HLOS > 7 d (Odds ratio = 0.629, P = 0.015). The cut-off of SA on postoperative day 2 was 30.6g/L, with an area under the curve of 0.86 and a negative predictive value of 100% for the prediction of HLOS ≤ 7 d. CONCLUSION: The SA level on postoperative day 2 was associated with the HLOS in patients undergoing emergency surgery for PPU. The pre- and post-operative albumin levels should be monitored, and infusion of human SA should be considered in a timely manner.

Bi's purse-string suture: an effective method for presacral venous bleeding.

Presacral venous bleeding (PSVB) is an intractable situation during rectal mobilization. Till now, various methods for PSVB are introduced, but each of them has limitations. This article aims to introduce an effective approach for PSVB, which is created by Professor Xiaogang Bi. In the case of PSVB, a purse-string suture which highlighted each stitch penetrates periosteum of sacrum was performed around the bleeding site. After that, the branches of presacral venous plexus around the bleeding site were compressed to the sacrum when the stitches were tightened, the blood flow of the venous branches was blocked by the thread across them, the bleeding was controlled, and then, the knot was tied. From April 24th 2017 to November 6th 2022, ten patients who suffered PSVB during surgery accepted Bi's suture. With Bi's suture, all of the ten cases of PSVB were controlled effectively. Nine of ten cases were controlled immediately only by Bi's suture, one case which accompanied with blood oozing of sacrum wound was controlled by Bi's suture, bone wax, and pelvic gauze packing. Bi's suture is an effective approach for PSVB. It could be easily performed without the need of special materials.

Causal associations between gut microbiota and sepsis: A two-sample Mendelian randomization study.

BACKGROUND: Targeting the gut microbiota may become a new therapeutic to prevent and treat sepsis. Nonetheless, the causal relationship between specific intestinal flora and sepsis is still unclear. METHODS: A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study (n = 18,340). The summary statistics of sepsis were obtained from the UK Biobank (n = 486,484). Inverse-variance weighted, weighted median and MR-Egger were used to examine the causal association between gut microbiota and sepsis. Cochrane's Q test, MR-Egger intercept test, MR-PRESSO Global test and Rucker's Q'-test were used for sensitivity analyses. The leave-one method was used for testing the stability of MR results, and Bonferroni-corrected was used to test the strength of the causal relationship between exposure and outcome. RESULTS: Nine intestinal microflora were found causally associated with sepsis, and 11 intestinal microflora were causally associated with 28-day death in sepsis. Among them, Order Victivallales had a strong causality with lower risk of sepsis (OR = 0.86, 95% CI: 0.78-0.94, p = .00165) and lower 28-day mortality of sepsis (OR = 0.68, 95% CI: 0.53-0.87, p = .00179) after Bonferroni-corrected test. No pleiotropy was detected. CONCLUSIONS: Through the two-sample MR analysis, we identified the specific intestinal flora that had a causal relationship with the risk and prognosis of sepsis at the level of gene prediction, which may provide helpful biomarkers for early disease diagnosis and potential therapeutic targets for sepsis.

Therapeutic effects of multidisciplinary individualized treatment for COVID-19 patients: the experience of a supporting medical team in Wuhan.

Background: The sudden outbreak of coronavirus disease 2019 (COVID-19) has brought people around the world into an abyss of suffering. At that time, there were no clear and effective means for the treatment of the virus. We prepared a medical team consisted of specialists in critical care, respiratory diseases, infections, gastroenterology, endocrinology, cardiology, cerebrovascular diseases, nephrology, rehabilitation, psychology, and nutrition. This study shared our multidisciplinary treatment experience in treating patients with COVID-19. Methods: Patients with positive SARS-CoV-2 swab test were divided into three groups: ordinary cases, severe cases and critical cases. Every patient received the multi-disciplinary comprehensive and individualized tailored treatment based on the specific situation of each patient. Patients' medical records, epidemiological, clinical, laboratory, radiological characteristics, Borg dyspnea score, Barthel index, self-rating anxiety scale (SAS) as well as treatment and outcome data were analyzed. Results: The mean age of the 90 patients was 61.88±15.25 years. Some patients without underlying disease had developed comorbidities such as hyperglycemia (24, 26.67%) and hypertension (9, 10%). With multidisciplinary individualized treatment, the patients' albumin level and Barthel index score increased significantly, while glucose level, blood pressure, and Nutrition Risk Screening 2002 (NRS-2002), Borg scale, and SAS values significantly decreased at discharge. The in-hospital mortality rate was 4.44%. However, there was still a gap in Nutrition Risk Screening, Borg dyspnea score and Barthel index between the critical cases and the ordinary and severe cases at discharge. We observed that the patients with more severe disease had significantly higher age, rates of hypertension, and mortality. The median hospitalization time of discharged patients was 19 days [interquartile range (IQR), 9.0-20.0 days]. Conclusions: Multidisciplinary collaboration and individualized treatment could effectively improve the general status of patients with different severity of COVID-19.

Mapping of lymph node dissection determined by the epicenter location and tumor extension for esophagogastric junction carcinoma.

Backgrounds: Previous studies identified the extent of lymph node dissection for esophagogastric junction (EGJ) carcinoma based on the metastatic incidence. The study aimed to determine the optimal extent and priority of lymphadenectomy based on the therapeutic efficacy from each station. Methods: The studies on the lymph node metastasis (LNM) and therapeutic efficacy index (EI) for EGJ carcinomas were identified until April 2022. The obligatory stations with the LNM rates over 5% and therapeutic EI exceeding 2% should be routinely resected for D2 dissection, whereas the optional stations with EI between 0.5% and 2% should be resected for D3 dissection in selective cases. Results: The survey yielded 16 eligible articles including 6,350 patients with EGJ carcinoma. The metastatic rates exceeded 5% at no. 1, 2, 3, 7, 9, 11p, and 110 stations and were less than 5% in abdominal no. 4sa~6, 8a, 10, 11d, 12a, and 16a2/b1 and mediastinal no. 105~112 stations. Consequently, obligatory stations with EI over 2% were largely determined by the epicenter location and located at the upper perigastric, lower mediastinal, and suprapancreatic zones, corresponding to those with rates of LNM over 5%. Consistent with the LNM rates less than 5%, the optional stations with EI between 0.5% and 2% were largely dependent on the degree of tumor extension toward the lower perigastric, splenic hilar (grecurvature), para-aortic (less curvature of the cardia), and middle or upper mediastinal zones. Conclusions: The obligatory stations can be resected as an "envelope-like" wrap by transhiatal proximal gastrectomy with lower esophagectomy, whereas the optional stations for dissection are indicated by the tumor extension. The extended gastrectomy is required for the lower perigastric in the stomach-predominant tumor with gastric involvement exceeding 5.0 cm, para-aortic dissection in the less curvature-predominant tumor and splenic hilar dissection in the grecurvature-predominant tumor whereas transthoracic subtotal esophagectomy is required for complete mediastinal dissection and adequate negative margin in the esophagus-predominant tumor with esophageal invasion exceeding 3.0 cm.

Diagnostic Potential of microRNAs in Extracellular Vesicles Derived from Bronchoalveolar Lavage Fluid for Pneumonia-A Preliminary Report.

Current clinical needs require the development and use of rapid and effective diagnostic indicators to accelerate the identification of pneumonia and the process of microbiological diagnosis. MicroRNAs (miRNAs) in extracellular vesicles (EVs) have become attractive candidates for novel biomarkers to evaluate the presence and progress of many diseases. We assessed their performance as biomarkers of pneumonia. Patients were divided into the pneumonia group (with pneumonia) and the control group (without pneumonia). We identified and compared two upregulated miRNAs in EVs derived from bronchoalveolar lavage fluid (BALF-EVs) between the two groups (PmiR-17-5p = 0.009; PmiR-193a-5p = 0.031). Interestingly, in cell-debris pellets and EVs-free supernatants derived from bronchoalveolar lavage fluid (BALF-cell-debris pellets and BALF-EVs-free supernatants), total plasma, and EVs derived from plasma (plasma-EVs), the expression of miR-17-5p and miR-193a-5p showed no difference between pneumonia group and control group. In vitro experiments revealed that miR-17-5p and miR-193a-5p were strikingly upregulated in EVs derived from macrophages stimulated by lipopolysaccharide. MiR-17-5p (area under the curve, AUC: 0.753) and miR-193a-5p (AUC: 0.692) in BALF-EVs are not inferior to procalcitonin (AUC: 0.685) in the diagnosis of pneumonia. Furthermore, miR-17-5p and miR-193a-5p in BALF-EVs had a significantly higher specificity compared to procalcitonin and could be served as a potential diagnostic marker. MiR-17-5p and miR-193a-5p in EVs may be involved in lung inflammation by influencing the forkhead box O (FoxO) signaling pathway and protein processing in endoplasmic reticulum. This study is one of the few studies which focused on the potential diagnostic role of miRNAs in BALF-EVs for pneumonia and the possibility to use them as new biomarkers for a rapid and early diagnosis.

Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/ß2-adrenoceptor/YKL-40 signaling pathway.

Objective: This study aimed to address the status, role, and mechanism of sympathetic nerve infiltration in the progression of stomach adenocarcinoma (STAD). Methods: Sympathetic nerve and its neurotransmitter NE, ß-ARs, and associated signaling molecules in the STAD tissues and the adjacent tissues from 46 STAD patients were examined using immunostaining, HPLC, and western blotting. The effects and mechanisms of ß2-AR activation on the proliferation, migration and invasion of AGS and SGC-7901 gastric cancer (GC) cell lines were examined using CCK-8, transwell, and western blotting assays. Correlations between genes and STAD survival were analyzed using bioinformatics. Results: Striking sympathetic nerve infiltration, elevations of NGF, TrkA, GAP43, TH, S100, NE, ß2-AR, YKL-40, syndecan-1, MMP9, CD206, and CD31 were observed in the STAD tissues compared to the adjacent tissues. Activation of ß2-AR in the two GC cell lines significantly amplified the expressions of NGF, YKL-40, MMP9, syndecan-1, p-STAT3 and p-ERK, and increased GC cell proliferation, migration and invasion. Bioinformatic analyses revealed positive correlations of NGF, ß2-AR, syndecan-1, and macrophage infiltration, respectively, with low survival of STAD, of ß2-AR respectively with STAT3, ERK1/2 (MAPK1/3), YKL-40, MMP9, and syndecan-1, and of YKL-40 with MMP9. Conclusion: Sympathetic nerves significantly infiltrated into human STAD tissues as a result of high NGF and TrkA expressions; elevated NE led to overactivation of ß2-AR-STAT3/ERK-YKL-40 signaling pathway, and finally caused cancer cell growth and invasion, M2 macrophage infiltration, angiogenesis, matrix degradation and STAD metastasis and progression.

Clinical Treatment Experience in Severe and Critical COVID-19.

Compared with other deadly diseases, the coronavirus disease 2019 (COVID-19) is highly infectious with a relatively low mortality rate. Although critical cases account for only 5% of cases, the mortality rate for the same is nearly 50%. Therefore, the key to the COVID-19 treatment is to effectively treat severe patients and reduce the transition from severe to critical cases. A retrospective study was carried out to evaluate outcomes of treatment in patients with severe and critical COVID-19 admitted to a COVID-19 special hospital in Wuhan, China. A total of 75 severe and critical COVID-19 patients were admitted and treated with immunomodulation as the main strategy combined with anti-inflammatory therapy and appropriate anticoagulation. Leukocyte levels in patients with 7-14 days of onset to diagnosis were significantly lower than in those with >14 days. Higher levels of globulin and D-dimer and lower lymphocyte levels were found in the older age group (>65 years) than in the middle-aged group (50-64 years). Patients with comorbidity had higher levels of inflammatory indicators. After treatment, 65 (86.67%) patients were cured, 7 (9.33%) had improved, and 3 (4.00%) had died. Median hospitalization duration was 23 days. Fatal cases showed continuously increased levels of globulin, dehydrogenase (LDH), hypersensitive C-reactive protein (hs-CRP), D-dimer, and cytokines during treatment. Time from onset to diagnosis, age, and comorbidity are important influencing factors on treatment effects. The occurrence of immunosuppression, "cytokine storm," and thrombosis may be an important cause of death in severely infected cases. In conclusion, high cure rate and low mortality suggested that immunomodulation combined with anti-inflammatory therapy and appropriate anticoagulant therapy is a good strategy for treatment of patients with severe and critical COVID-19.

Clinical descriptive analysis of severe Pneumocystis jirovecii pneumonia in renal transplantation recipients.

Pneumocystis jirovecii (P. jirovecii) pneumonia (PJP) is an opportunistic fungal infection after renal transplantation, which is always severe, difficult to diagnose, combined with multiple complications and have poor prognosis. We retrospectively analyzed clinical data, including risk factors, diagnosis, treatment and complications of seven clinical cases suffered with severe PJP after renal transplantation in our department in 2019. All the seven recipients were routinely prescribed with PJP prophylaxis after renal transplantation, and six of them suffered acute graft rejection before the infection. P. jirovecii sequence was identified in blood or broncho-alveolar lavage fluid (BALF) by the metagenomic next-generation sequencing (mNGS) in all patients. All the patients were improved with the therapy trimethoprim-sulfamethoxazole (TMP-SMX) combined with caspofungin for the PJP treatment, but suffered with complications including renal insufficiency, leukopenia, thrombocytopenia, gastrointestinal bleeding, mediastinalemphysema, pulmonary hemorrhage, and hemophagocytic syndrome and other severe infections. Taken together, mNGS is a powerful tool that could be used to diagnose PJP in renal transplantation recipients. And PJP prophylaxis should be prescribed during and after treatment for acute rejection. TMP-SMX is the first-line and effective drug for PJP treatment, but the complications are always life-threatening and lead to poor prognosis. We should pay attention to these life-threatening complications.

Co-Infection Pneumonia with Mycobacterium abscessus and Pneumocystis jiroveci in a Patient without HIV Infection Diagnosed by Metagenomic Next-Generation Sequencing.

INTRODUCTION: Co-infection pneumonia with Mycobacterium abscessus (M. abscessus) and Pneumocystis jirovecii (P. jirovecii) is rarely reported in previously healthy patients without HIV infection. The diagnosis of pneumonia of M. abscessus and P. jirovecii remains challenging due to its nonspecific clinical presentation and the inadequate performance of conventional diagnostic methods. CASE REPORT: We report the case of a 44-year-old previously healthy male transferred to our hospital in February 2020 with a 4-month history of productive cough and one month of intermittent fever. At local hospital, the metagenomic next-generation sequencing(mNGS) detected P. jirovecii sequences in blood; with the antifungal therapy (Caspofungin, trimethoprim-sulfamethoxazole [TMP-SMX] and methylprednisolone [MP]), the patient still had hypoxemia, cough and fever. Then he was transferred to our hospital, the mNGS of bronchoalveolar lavage fluid (BALF) detected the sequences of M. abscessus and P. jirovecii. CD4+ T-lymphocytopenia in the peripheral blood cells was presented and HIV serology was negative. Caspofungin, TMP-SMX, clindamycin and MP were used to treat P. jirovecii pneumonia (PJP). Moxifloxacin, imipenem cilastatin and linezolid were used to treat M. abscessus infection. Clinical progress was satisfactory following antifungal combined with anti-M. abscessus therapy. CONCLUSION: Co-infection pneumonia with M. abscessus and P. jirovecii as reported here is exceptionally rare. mNGS is a powerful tool for pathogen detection. M. abscessus infection could be a risk factor for P. jirovecii infection. This case report supports the value of mNGS in diagnosing of M. abscessus and P. jirovecii, and highlights the inadequacies of conventional diagnostic methods.

High Expression of Interleukin-2 Receptor Subunit Gamma Reveals Poor Prognosis in Human Gastric Cancer.

Precision medicine for gastric cancer (GC) is still an unsolved issue, because most available target drugs are not specifically designed for GC. Exploring novel signaling molecules with target value for GC is in urgent need. This study aimed to reveal that interleukin-2 receptor subunit gamma (IL2RG) is such a key molecule in human GC progression. GC tissues and paracancerous gastric tissues were collected from 7 patients (5 males and 2 females) during tumor radical excision surgery. These tissues were used to identify the differentially expressed genes (DEGs) with RNA-seq and serial bioinformatics analyses including Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, gene expression profiling interactive analysis (GEPIA), and survival analysis. RT-qPCR and western blotting were performed to compare the mRNA and protein expression levels of IL2RG between GC tissues and adjacent normal gastric tissues as well as between GC cell line SGC-7901 and normal gastric epithelial cell line GES-1. Results showed striking elevations of IL2RG both in the mRNA and protein levels in GC tissues and human gastric cancer SGC-7901 cell line compared, respectively, with the adjacent normal gastric tissues and normal GES-1 cells, and higher IL2RG expression was associated with lower survival. Analyses on the GSE29272 and GSE15459 datasets from Gene Expression Omnibus verified that IL2RG was highly expressed in GC patients and was associated with poor overall survival. In addition, molecular docking showed that a small molecule, resatorvid (TAK 242), might be an inhibitor of IL2RG. We conclude that IL2RG is overexpressed in advanced GC and is associated with low survival. IL2RG may serve as a biomarker of GC progression and poor prognosis.

Rare case of intracranial hemorrhage associated with seoul virus infection diagnosed by metagenomic next-generation sequencing.

BACKGROUND: Seoul virus (SEOV) is a Hantavirus and the causative pathogen of Hemorrhagic Fever with Renal Syndrome (HFRS). Diagnosing SEOV infection is difficult because the clinical presentations are often undistinguishable from other viral or bacterial infections. In addition, diagnostic tools including serological and molecular assays are not readily available in the clinical settings. CASE REPORT: A 57-year-old male presented with fever and a sudden loss of consciousness in November 2019. Computed tomography (CT) scan showed subdural hematoma, subfalcine herniation, and brain infarction. He developed thrombocytopenia and elevated transaminases, but no rashes or obvious kidney damage. He reported having a rat bite. HFRS was suspected. The Hantavirus IgG was positive, and the metagenomic next-generation sequencing (mNGS) detected SEOV sequences directly in the blood. CONCLUSION: This report highlights the importance of suspecting SEOV infection in febrile patients with thrombocytopenia and elevated liver enzymes despite the absence of hemorrhagic manifestations of skin and renal syndromes. Next-generation sequencing is a powerful tool for pathogen detection. Intracranial hemorrhage and brain infarction as extrarenal manifestations of HFRS are rare but possible as demonstrated in this case.

Surface molecularly imprinted polymer based on core-shell Fe3O4@MIL-101(Cr) for selective extraction of phenytoin sodium in plasma.

Core-shell magnetic Fe3O4@MIL-101(Cr) nanoparticles were synthesized via layer-by-layer self-assembly method. Using Fe3O4@MIL-101(Cr) as support, Fe3O4@MIL-101(Cr)@MIP was prepared with phenytoin as template, acrylamide as functional monomer, ethylene glycol dimethacrylate as cross-linker, methanol and acetonitrile as porogen, azoisobutyronitrile as initiator. The materials were characterized by a serious of characterization experiments. The prepared Fe3O4@MIL-101(Cr)@MIP was demonstrated to possess good separability, large adsorption capability, excellent adsorption selectivity, good durability and reusability via adsorption experiments. Subsequently, a magnetic solid phase extraction method (MSPE) based on Fe3O4@MIL-101(Cr)@MIP combined with high performance liquid chromatography-ultraviolet detector (HPLC-UV) was established for the determination of phenytoin sodium in plasma samples. Experimental parameters including pH, the amount of adsorbent, extraction time, elution conditions, the concentration of NaCl were investigated to optimize extraction process. The method was validated. The linearity was observed in the range of 0.05-40 µg mL-1 with a lower limit of quantification of 0.05 µg mL-1. The calibration equations were y = 0.2514x + 0.0319 (r2 = 0.9938), y = 0.2888x + 0.0472 (r2 = 0.9943), y = 0.2565x + 0.0418 (r2 = 0.9976), respectively. The recoveries ranged from 89.2 to 94.3%, intra- and inter-day precision (RSDs) ranged from 2.1 to 9.7% and 2.9-9.2%, respectively. The established MSPE-HPLC-UV method was time-saving, sensitive, accurate, environmental friendly, and drastically reduced the complex matrix interferences. The established method was successfully applied for phenytoin sodium determination in real plasma samples, providing new directions for therapeutic drug monitoring.

Impact of surgical strategies on the survival of gallbladder cancer patients: analysis of 715 cases.

OBJECTIVE: The aim of the study is to evaluate the impact of application of surgical strategies at different cancer stages on the survival of gallbladder cancer (GBC) patients. METHODS: The patients with GBC were divided into 3 groups according to their received surgical strategies: simple resection (full-thickness cholecystectomy for removal of primary tumor site), radical resection (gallbladder bed removal combined with partial hepatectomy), and palliative surgery (treatment at advanced stages). The overall survival (OS) of GBC patients who were received different surgical strategies was compared. RESULTS: Survival analysis showed that radical resection had a best OS at clinical stage II, and simple resection had a best OS at tumor clinical stage IV. Cox hazard proportional regression analysis showed that more advanced tumor stages, tumor location of gallbladder body or neck, and CA199 ≥ 27 U/mL were the major risk factors for the OS of GBC. CONCLUSIONS: At tumor stage II, radical resection should be the most effective surgical therapy for GBC. However, the effect of radical resection at advanced stages could be restricted. The utilization of radical resection should be increased at tumor stage II for a better long-term survival outcome.

Association between arterial hyperoxia and mortality in critically ill patients: A systematic review and meta-analysis.

PURPOSE: The relationship between arterial hyperoxia exposure and clinical outcome is under increasing scrutiny. We therefore performed an update meta-analysis to evaluate the effect of arterial hyperoxia on hospital mortality in critically ill adults. METHODS: We searched relevant articles for trials that investigated the relationship between arterial hyperoxia and mortality in critically ill adults. The end-point was hospital mortality of critically ill patients. RESULTS: Three RCTs and 26 cohort studies involving 257,223 patients were identified. Hyperoxia exposure was associated with increased mortality in critically ill patients (crude OR 1.42, 95% CI 1.26-1.61; adjusted OR 1.20, 95% CI 1.09-1.32). There was no change in significance for outcome in meta-analysis of RCTs (OR 1.36; 95% CI 1.04-1.77) and sensitivity analysis of the included prospective studies (OR 1.32; 95% CI 1.04-1.67). This association was also established in patients admitted to critical care units following cardiac arrest (adjusted OR 1.32; 95% CI 1.12-1.56), ischemic stroke (crude OR 1.31; 95% CI 1.03-1.65) and intracerebral hemorrhage (crude OR 1.47; 95% CI 1.19-1.81). CONCLUSIONS: The results of current meta-analysis suggest that arterial hyperoxia may be associated with increased hospital mortality in critically ill patients.

A life-threatening duodenal ulcer hemorrhage due to previously unknown primary hyperparathyroidism.

Peptic ulcer bleeding due to primary hyperparathyroidism is extremely rare. We report a case of a 42-year-old male with life-threatening acute upper gastrointestinal bleeding secondary to a duodenal ulcer and a history of kidney stones. Gastroscopic therapy, Billroth II gastrointestinal anastomosis and angiographic embolization were sequentially conducted to arrest the hemorrhage. A complete investigative work-up revealed that the duodenal ulcer bleeding was due to primary hyperparathyroidism coexisting with a parathyroid adenoma. Following this event, the patient developed a severe abdominal cavity infection and sepsis. An elective parathyroidectomy was performed, and the histology was confirmed to be a typical parathyroid adenoma. Postoperatively, the patient's calcium and parathyroid levels were normalized. Attention should be paid to patients with an upper gastrointestinal ulcer, especially when it is accompanied by kidney stones.

Improving the Secretion Yield of the ß-Galactosidase Bgal1-3 in Pichia pastoris for Use as a Potential Catalyst in the Production of Prebiotic-Enriched Milk.

In this study, three kinds of milk were treated with the ß-galactosidase Bgal1-3 (4 U/mL), resulting in 7.2-9.5 g/L galactooligosaccharides (GOS) at a lactose conversion of 90-95%. Then, Bgal1-3 was secreted from Pichia pastoris X33 under the direction of an α-factor signal peptide. After cultivation for 144 h in a flask culture with shaking, the extracellular activity of Bgal1-3 was 4.4 U/mL. Five more signal peptides (HFBI, apre, INU1A, MF4I, and W1) were employed to direct the secretion, giving rise to a more efficient signal peptide, W1 (11.2 U/mL). To further improve the secretion yield, recombinant strains harboring two copies of the bgal1-3 gene were constructed, improving the extracellular activity to 22.6 U/mL (about 440 mg/L). This study successfully constructed an engineered strain for the production of the ß-galactosidase Bgal1-3, which is a promising catalyst in the preparation of prebiotic-enriched milk.

Seroprevalence of Toxoplasma gondii Infection in Patients of Intensive Care Unit in China: A Hospital Based Study.

The objective of this study was to estimate the seroprevalence of Toxoplasma gondii infection in 394 patients of intensive care unit (ICU) in a hospital between April 2010 and March 2012 and analyze the association between T. gondii infection and ICU patients according to the species of disease. Toxoplasma serology was evaluated by ELISA method using a commercially available kit. Data of patients were obtained from the patients, informants, and medical examination records. Seventy-four (18.78%) of 394 patients were positive for anti-T. gondii IgG antibodies demonstrating latent infection. Of these, the highest T. gondii seroprevalence was found in the age group of 31-45 years (27.45%), and the lowest was found in the age group of <30 years (12.5%). In addition, females (21.6%) had a higher seroprevalence than males (18.36%). With respect to the species of disease, the patients with kidney diseases (57.14%), lung diseases (27.84%), and brain diseases (24%) had high T. gondii seroprevalence. The present study represents the first survey of T. gondii seroprevalence in ICU patients in China, revealing an 18.78% seropositivity. Considering the particularities of ICU patients, molecular identification, genetic characterization, and diagnosis of T. gondii should be considered in future study.

Outer membrane vesicles isolated from two clinical Acinetobacter baumannii strains exhibit different toxicity and proteome characteristics.

Outer membrane vesicles (OMVs) are well-characterized virulence factors produced by Gram-negative bacteria. Here, we isolated two clinical Acinetobacter baumannii strains, the multidrug-resistant A. baumannii (MDRAb) A38 and non-MDRAb 5806. Strain A38 produced more abundant OMVs than strain 5806 when cultured to the early stationary phase. The results from cell proliferation assays and real-time PCR analyses indicated that A38 OMVs induced more powerful cytotoxicity and stronger innate immune responses compared with 5806 OMVs. Moreover, SDS-PAGE and LC-MS/MS analyses revealed that A38 OMVs contained more virulence factors, including Omp38, EpsA, Ptk, GroEL, hemagglutinin-like protein, and FilF. Taken together, the results of the present study suggest that MDRAb might produce abundant OMVs with more virulent factors facilitating the worse outcome, a finding that merits further study.