Facilely Prepared Carbon Dots as Effective Anode Modifier for Enhanced Performance of Microbial Fuel Cells.

Microbial fuel cells (MFCs) are a promising technology for obtaining energy in wastewater. Effective extracellular electron transfer is one of the key factors for its practical application. In this work, carbon dots (CDs) enriched with oxygen-containing groups on the surface were synthesized as an efficient anode modifier using a simple hydrothermal method and common reactants. The experimental findings indicated that anodes modified with CDs exhibited increased electrical conductivity and greater hydrophilicity. These modifications facilitated increased microorganism loading and contributed to enhancing electrochemical processes within the anode biofilm. The CD-modified MFCs exhibited higher maximum power density (661.1 ± 42.6 mW·m-2) and open-circuit voltage (534.50 ± 6.4 mV), which were significantly better than those of the blank group MFCs (484.1 ± 14.1 mW·m-2 and 447.50 ± 12.1 mV). The use of simple carbon materials to improve the microbial loading on the MFCs anode and the electron transfer between the microbial-electrode may provide a new idea for the design of efficient MFCs.

Recent Advancement in Inhaled Nano-drug Delivery for Pulmonary, Nasal, and Nose-to-brain Diseases.

Pulmonary, nasal, and nose-to-brain diseases involve clinical approaches, such as bronchodilators, inhaled steroids, oxygen therapy, antibiotics, antihistamines, nasal steroids, decongestants, intranasal drug delivery, neurostimulation, and surgery to treat patients. However, systemic medicines have serious adverse effects, necessitating the development of inhaled formulations that allow precise drug delivery to the airways with minimum systemic drug exposure. Particle size, surface charge, biocompatibility, drug capacity, and mucoadhesive are unique chemical and physical features that must be considered for pulmonary and nasal delivery routes due to anatomical and permeability considerations. The traditional management of numerous chronic diseases has a variety of drawbacks. As a result, targeted medicine delivery systems that employ nanotechnology enhancer drug efficiency and optimize the overall outcome are created. The pulmonary route is one of the most essential targeted drug delivery systems because it allows the administering of drugs locally and systemically to the lungs, nasal cavity, and brain. Furthermore, the lungs' beneficial characteristics, such as their ability to inhibit first-pass metabolism and their thin epithelial layer, help treat several health complications. The potential to serve as noninvasive self-administration delivery sites of the lung and nasal routes is discussed in this script. New methods for treating respiratory and some systemic diseases with inhalation have been explored and highlight particular attention to using specialized nanocarriers for delivering various drugs via the nasal and pulmonary pathways. The design and development of inhaled nanomedicine for pulmonary, nasal, and respiratory medicine applications is a potential approach for clinical translation.

Effects of ondansetron treatment on outcomes of critically ill patients with myocardial infarction partly through its anti-inflammatory activity.

Background: Patients with myocardial infarction (MI) in intensive care units (ICU) are at high risk of death. Whether treatment with ondansetron (OND) at an early stage plays a protective role in critically ill patients with MI and its underlying mechanism remains unclear. Methods: A total of 4486 patients with MI were enrolled in the study cohort from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into OND-medication groups or not. Propensity score matching (PSM) and regression analysis were performed to investigate the effect of OND on patients, accompanied by sensitivity analysis to evaluate the robustness of the results. Integrated with causal mediation analysis (CMA), we investigated the potential causal pathway mediated by the palate-to-lymphocyte ratio (PLR) between early OND treatment and clinical outcomes. Results: Among patients with MI, 976 of them were treated with OND at the early stage while 3510 patients were not. The all-cause in-hospital mortality rate was significantly lower in the OND-medication group (5.6% vs 7.7%), accompanied by lower 28-day mortality (7.8% vs 11.3%) and 90-day mortality (9.2% vs 13.1%) rates. PSM analysis further confirmed the results for in-hospital mortality (5.7% vs 8.0%), 28-day mortality (7.8% vs 10.8%), and 90-day mortality (9.2% vs 12.5%). After adjusting for confounders, multivariate logistic regression analysis revealed that OND was associated with decreased in-hospital mortality (OR = 0.67, 95% CI: 0.49-0.91), and Cox regression confirmed the results for 28-day mortality and 90-day mortality with HR = 0.71 and 0.73, respectively. Most importantly, CMA demonstrated that the protective effect of OND on patients with MI was mediated by its anti-inflammatory effect through the regulation of PLR. Conclusion: Early use of OND in critically ill patients with MI may exert protective effects by reducing in-hospital mortality and 28- and 90-day mortality. The beneficial effects of OND on these patients were exerted through anti-inflammatory effects, at least in part.

[Simultaneous determination of 22 antibiotics in environmental water samples by solid phase extraction-high performance liquid chromatography-tandem mass spectrometry].

The widespread and frequent use of antibiotics to treat diseases or encourage animal growth has resulted in their persistence and accumulation in water, soil, and sediments. As a typical emerging pollutant in the environment, antibiotics have become an important research focus in recent years. Antibiotics are commonly found at trace levels in water environments. Unfortunately, the determination of various types of antibiotics, all of which exhibit different physicochemical properties, remains a challenging endeavor. Thus, developing pretreatment and analytical techniques to achieve the rapid, sensitive, and accurate analysis of these emerging contaminants in various water samples is an essential undertaking.In this paper, a solid phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method for the simultaneous determination of 22 antibiotics including 4 penicillins, 12 quinolones and 6 macrolides in environmental water samples was developed. Based on the characteristics of the screened antibiotics and sample matrix, the pretreatment method was optimized, focusing on the SPE column, pH of the water sample, and amount of ethylene diamine tetra-acetic acid disodium (Na2EDTA) added to the water sample. Prior to extraction, a 200 mL water sample was added with 0.5 g of Na2EDTA and pH-adjusted to 3 using sulfuric acid or sodium hydroxide solution. Water sample enrichment and purification were achieved using an HLB column. HPLC separation was carried out on a C18 column (100 mm×2.1 mm, 3.5 µm) via gradient elution with a mobile phase composed of acetonitrile and 0.15% (v/v) formic acid aqueous solution. Qualitative and quantitative analyses were performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode using an electrospray ionization source. The results showed correlation coefficients greater than 0.995, indicating good linear relationships. The method detection limits (MDLs) and limits of quantification (LOQs) were in the ranges of 2.3-10.7 ng/L and 9.2-42.8 ng/L, respectively. The recoveries of target compounds in surface water at three spiked levels ranged from 61.2% to 157%, with relative standard deviations (RSDs) of 1.0%-21.9%. The recoveries of target compounds in wastewater at three spiked levels were 50.1%-129%, with RSDs of 1.2%-16.9%. The method was successfully applied to the simultaneous determination of antibiotics in reservoir water, surface water, sewage treatment plant outfall, and livestock wastewater. Most of the antibiotics were detected in watershed and livestock wastewater. Lincomycin was detected in 10 surface water samples, with a detection frequency of 90%, and ofloxacin showed the highest contents (127 ng/L) in livestock wastewater. Therefore, the present method exhibits excellent performance in terms of MDLs and recoveries compared with previously reported methods. The developed method presents the advantages of small water sample volumes, wide applicability, and fast analysis times; thus, it can be considered a rapid, efficient, and sensitive analytical method with excellent potential for monitoring emergency environmental pollution. The method could also provide a reliable reference for formulating antibiotic residue standards. The results provide strong support for and an improved understanding of the environmental occurrence, treatment, and control of emerging pollutants.

Role of the heat shock protein family in chlorpromazine-induced cardiotoxicity.

Chlorpromazine (CPZ), a first-generation antipsychotic, is widely used in treating schizophrenia and other psychiatric disorders. However, CPZ is also associated with an increased likelihood of sudden cardiac death, and the underlying mechanisms remain unclear. In our study, we aimed to determine the CPZ-induced changes in some members of the heat shock protein family in rat hearts and further explore the possible mechanisms of CPZ-induced cardiotoxicity. Twenty-four Sprague Dawley rats were randomly divided into three groups (n = 8 per group): control, low dose (33.216 mg/kg) and high dose (94.211 mg/kg). CPZ administration induced hypothermia in rats. Pathological changes, including ischaemia and hypoxia, were observed in rat hearts. Furthermore, the serum levels of cardiac Troponin T (c-TN-T) and brain natriuretic peptide (BNP) were elevated in the CPZ-exposed groups. Meanwhile, the protein and gene expression of HSP70, HSP60, HSP27 and HSP10 significantly differed between the CPZ-exposed and control groups. We conclude that acute CPZ exposure could lead to myocardial injury in rats, in which HSPs might play a crucial role. Further investigations are required to elucidate the underlying mechanisms.

The preliminary development and psychometric properties of the Psychotherapy Side Effects Scale.

BACKGROUND: Side effects in psychotherapy are common and have a negative impact on patients or clients. However, effective evaluation tools are still lacking and have not been fully studied. The present study aims to develop a scale with good reliability and validity to measure the side effects of psychotherapy. METHODS: The 25 items in the Psychotherapy Side Effects Scale (PSES) were condensed and distributed to 420 subjects online to test its psychometric properties. RESULTS: The internal consistency of the PSES was satisfactory to excellent (Cronbach's ɑ coefficient was .95, and the Guttman split-half coefficient was 0.88). A statistically significant negative correlation between the satisfaction score and the total score of the PSES was shown (r = -0.51, p < .001). The PSES could effectively discriminate between two groups with and without side effects (F = 250.95, p < .001) and was able to predict the occurrence of side effects in psychotherapy with an area under curve of 0.932 and a 95% confidence interval of 0.900-0.964 (p < .001). A cutoff was set at 36 points in total PSES score, from which the maximum Youden's index (= 0.72) could be obtained. The positive rate of the PSES was 24% (101/420). CONCLUSION: The PSES showed good internal consistency, content validity, concurrent validity, discriminant validity and predictive validity in evaluating and identifying side effects in psychotherapy. More advanced reliability testing methods and structural validity testing for PESE need to be practiced in the future to better serve clinical practice.

An in silico and in vitro integrated analysis method to reveal the curative mechanisms and pharmacodynamic substances of Bufei granule on chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high disability and mortality. Clinical studies have shown that the Traditional Chinese Medicine Bufei Granule (BFG) has conspicuous effects on relieving cough and improving lung function in patients with COPD and has a reliable effect on the treatment of COPD, whereas the therapeutic mechanism is vague. In the present study, the latent bronchodilators and mechanism of BFG in the treatment of COPD were discussed through the method of network pharmacology. Then, the molecular docking and molecular dynamics simulation were performed to calculate the binding efficacy of corresponding compounds in BFG to muscarinic receptor. Finally, the effects of BFG on bronchial smooth muscle were validated by in vitro experiments. The network pharmacology results manifested the anti-COPD effect of BFG was mainly realized via restraining airway smooth muscle contraction, activating cAMP pathways and relieving oxidative stress. The results of molecular docking and molecular dynamics simulation showed alpinetin could bind to cholinergic receptor muscarinic 3. The in vitro experiment verified both BFG and alpinetin could inhibit the levels of CHRM3 and acetylcholine and could be potential bronchodilators for treating COPD. This study provides an integrating network pharmacology method for understanding the therapeutic mechanisms of traditional Chinese medicine, as well as a new strategy for developing natural medicines for treating COPD.

Melatonin Attenuates Mitochondrial Damage in Aristolochic AcidInduced Acute Kidney Injury

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Bioinformatics analysis and key gene verification of sepsis myocardial macrophage microarray data based on GEO database / 中华心血管病杂志

Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.

Safety and efficacy of transcatheter closure of Fontan fenestration with atrial septal occluder / 中华心血管病杂志

Objective: To assess the safety and efficacy of transcatheter fenestration closure following Fontan procedure with an atrial septal occluder. Methods: This is a retrospective study. The study sample consists of all consecutive patients who underwent closure of a fenestrated Fontan baffle at Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine between June 2002 and December 2019. The indications of Fontan fenestration closure included that normal ventricular function, targeted drugs for pulmonary hypertension and positive inotropic drugs were not required prior the procedure; and the Fontan circuit pressure was less than 16 mmHg (1 mmHg=0.133 kPa) and no more than a 2 mmHg increase during test occlusion of the fenestration. Electrocardiogram and echocardiography were reviewed at 24 hours, 1, 3, 6 months and annually thereafter post procedure. Follow-up information including clinical events and complications related to Fontan procedure was recorded. Results: A total of 11 patients, including 6 males and 5 females, aged (8.9±3.7) years old were included. The types of Fontan were extracardiac conduits (7 cases) and intra-atrial duct (4 cases). The interval between percutaneous fenestration closure and the Fontan procedure was (5.1±2.9) years. One patient reported recurrent headache after Fontan procedure. Successful fenestration occlusion with atrial septal occluder was achieved in all patients. Compared with prior closure, Fontan circuit pressure ((12.72±1.90) mmHg vs. (12.36±1.63) mmHg, P<0.05), and aortic oxygen saturation ((95.11±3.11)% vs. (86.35±7.26)%, P<0.01) were increased. There were no procedural complications. At a median follow-up of (3.8±1.2) years, there was no residual leak and evidence of stenosis within the Fontan circuit in all patient. No complication was observed during follow-up. One patient with preoperative headache did not have recurrent headache after closure. Conclusions: If the Fontan pressure is acceptable by test occlusion during the catheterization procedure, Fontan fenestration could be occluded with the atrial septum defect device. It is a safe and effective procedure, and could be used for occlusion of Fontan fenestration with varying sizes and morphologies.

"Accordion" technique to promote bony union at the docking site in the treatment of tibial bone defects by Ilizarov technique / 中华创伤骨科杂志

Objective:To evaluate the effect of "accordion" technique on promoting bony union at the docking site in the treatment of tibial bone defects by bone transport.Methods:A retrospective study was conducted to analyze the data of 11 patients with tibial bone infection who had been admitted to Department of Orthopedics, The Second Hospital of Shanxi Medical University from November 2017 to February 2019. There were 10 males and 1 female with an age of (47.0±9.7) years. Seven patients were infected after internal/external fixation for open fractures and 4 cases after internal fixation for closed fractures. After surgical debridement, sensitive antibiotic bone cement was implanted, and dead or infected bone segments were radically resected. In all patients, the resulting bone defects of (6.6±2.9) cm were fixated by an Ilizarov ring external fixator and filled by bone transport. The "accordion" technique was used after the bone segments touched the docking site. The closure time, "accordion" time, bony union time and complications during bone transport were recorded.Results:None of the patients underwent bone grafting. This case series was followed up for (2.7±0.5) years. The closure time was (30.8±6.8) weeks, the "accordion" time (43.1±8.4) days, and the bony union time (31.6±9.0) weeks. None of the patients had obvious pain. Ankle stiffness was observed in 3 patients and traumatic equinus deformity in 1 patient.Conclusions:The "accordion" technique based on the Illizarov technique can accelerate mineralization of the bone segments transported, promote the bony union at the docking site, and effectively solve the problem of tibial bone defects without surgical bone grafting.

Low diastolic blood pressure and adverse outcomes in inpatients with acute exacerbation of chronic obstructive pulmonary disease: A multicenter cohort study / 中华医学杂志(英文版)

BACKGROUND@#Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients.@*METHODS@#Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes.@*RESULTS@#Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality.@*CONCLUSION@#Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients.@*CLINICAL TRIAL REGISTRATION@#Chinese Clinical Trail Registry, No. ChiCTR2100044625.

Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.

Prevention and management of pancreatic fistula after pancreatoduodenectomy with precise and comprehensive opinion / 中华消化外科杂志

Pancreaticoduodenectomy (PD) is a major operation of abdominal surgery, with high risk, complex operation, more complications and high mortality. Pancreatic fistula is the main cause of death after PD. Due to its complexity and obstinacy, pancreatic fistula has become the top challenge of pancreatic surgery. The authors review the relevant literature and summarize the prevention and management of pancreatic fistula after PD, such as the optimization strategies for pancreatic anastomosis, the use of external stents, prophylactic drains in surgical field, the applica-tion of somatostatin and its analogues, and whole-course nutrition management, based on the precise and comprehensive opinion, in order to provide reference for improving the prevention and treatment of pancreatic fistula after PD.

Treatment and prognosis of patients of G3 nonfunctional pancreatic neuroendocrine tumors with proliferation index of Ki-67<55% / 中华消化外科杂志

Objective:To investigate the treatment and prognosis of patients of G3 non-functional pancreatic neuroendocrine tumors (pNETs) with proliferation index of Ki-67 <55%.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 15 G3 non-functional pNETs patients with proliferation index of Ki-67<55% who were admitted to Zhongshan Hospital of Fudan University from April 2014 to April 2020 were collected. There were 11 males and 4 females, aged (58±10)years. All patients underwent radical resection of the primary lesion. Obser-vation indicators: (1) treatment; (2) postoperative pathological characteristics; (3) follow-up. Measure-ment data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3) or M(range). Count data were described as absolute numbers. The Pearson correlation analysis was used to verify the correlation between variables. Kaplan-Meier method was used to draw survival curve and calculate survival rate. Log-Rank test was used for survival analysis. Results:(1) Treatment. All 15 G3 nonfunctional pNETs patients underwent radical resection of the primary lesion of pancreas, including 5 cases receiving pancreati-coduodenectomy, 10 cases receiving distal pancreatectomy with splenectomy. There were 5 patients with simultaneous liver oligometastasis who underwent combined segmental (lobectomy) hepatectomy. All 15 patients had negative tumor margin, and the operation time and volume of intraoperative blood loss of 15 patients was 120(90,210)minutes and 200(50,300)mL, respectively. None of patient had complications ≥Ⅲ grade of the Clavien-Dindo classification during the postoperative 30 days. Of the 15 patients, there were 5 cases receiving comprehensive treatment based on CAPTEM chemo-therapy (temozolomide combined with capecitabine), 2 cases receiving local interventional therapy, 2 cases receiving CAPTEM chemotherapy, 1 case receiving local interventional therapy combined with molecular targeted therapy, 1 case receiving local interventional therapy combined with long acting somatostatin therapy, 1 cases receiving long acting somatostatin therapy combined with molecular targeted therapy, and 3 cases without postoperative treatment. (2) Postoperative patholo-gical characteristics. The tumor diameter of 15 patients was 3.3(range, 0.5-6.0)cm. There were 2 cases with tumor diameter <2 cm, 13 cases with tumor diameter ≥2 cm. The number of lymph nodes dissected and number of lymph nodes metastatic was 6(4, 10) and 2(1,3) in 15 patients, respectively, including 12 cases with positive lymph node metastasis. Of the 15 patients, there were 5 cases with tumor invasion of adjacent organ, 5 cases with simultaneous liver metastasis, 8 cases with perineural invasion and 8 cases with vascular invasion. There were 3, 7, and 5 patients with stage Ⅱ, stage Ⅲ, and stage Ⅳ of pathological TNM staging, respectively. The proliferation index of Ki-67 and mitotic count was 32%±9% and (11±9)/10 high power field in the primary lesion of 15 patients, respectively, and there was no correlation between proliferation index of Ki-67 and mitotic count ( P>0.05). (3) Follow-up. All 15 patients were followed up after surgery for (55±24)months. The median survival time of 15 patients was 78(range, 43-113)months, with 1-, 3-, 5-year overall survival rate as 100%, 92%, 62%, respectively. During the follow up, 9 of the 15 patients underwent tumor recurrence, with the recurrence time as 20(14, 44)months. There were 8 patients died of tumor recurrence or metastasis. The median survival time was 86(range, 51-120)months in 5 patients receiving comprehensive treatment based on CAPTEM chemotherapy, versus 53(range, 45-60)months in 10 patients receiving other postoperative adjuvant therapy or without postoperative treatment, showing a significant difference between them ( χ2=4.21, P<0.05). Conclusion:The prognosis of patients of G3 nonfunctional pNETs with proliferation index of Ki-67<55% undergoing radical resection combined with postoperative comprehensive treatment based on CAPTEM chemotherapy in better than that of patients receiving other postoperative adjuvant therapy or without posto-perative treatment.

Correlation between serum SOST, DKK-1 levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery / 中华内分泌外科杂志

Objective:To investigate the correlation between serum recombinant sclerostin (SOST) and dickkopf-related protein 1 (DKK-1) levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery.Methods:A total of 110 patients diagnosed with osteoporosis after differentiated thyroid cancer surgery were recruited as the study group, and another 110 patients without osteoporosis diagnosed after differentiated thyroid cancer surgery were recruited as the control group. The general data, bone mineral density, serum SOST, DKK-1 levels and bone metabolism indicators N-terminal propeptide of type I procollagen (PINP), bone alkaline phosphatase (BALP), beta-isomerized C-telopeptide (β-CTX), 25-hydroxyvitamin D3 [25- (OH) D3] levels were compared between the two groups. The correlation between serum SOST, DKK-1 levels and bone metabolism indexes was analyzed, and the risk factors affecting the formation of osteoporosis were explored.Results:The T value of bone mineral density in the study group (-3.27±0.92) was significantly lower than that in the control group (-1.23±0.27, t=22.32, P<0.001). The serum SOST (15.84±1.34, t=32.53, P<0.001) and DKK-1 (5.96±1.40, t=4.82, P<0.001) levels in the study group were significantly higher than those in the control group (SOST: 10.24±1.21, DKK-1: 5.05±1.40). The serum PINP (40.95±9.84, t=7.59, P<0.001), BALP (23.14±5.26, t=5.06, P<0.001) and β-CTX (1.07±0.54, t=4.96, P<0.001) in the study group were significantly higher than those in the control group (31.48±8.64, 19.64±4.99, 0.78±0.29), and the 25- (OH) D3 level (13.68±4.49) was significantly lower than that of the control group (18.31±5.72, t=6.68, P<0.001). Serum SOST was positively correlated with PINP ( r=0.33, P=0.001), BALP ( r=0.23, P=0.016) and β-CTX ( r=0.19, P=0.046), but not with 25- (OH) D3 ( r=-0.09, P=0.349). Serum DKK-1 was positively correlated with PINP ( r=0.19, P=0.044), BALP ( r=0.26, P=0.007) and β-CTX ( r=0.21, P=0.028), but not with 25- (OH) D3 ( r=-0.16, P=0.088). Serum SOST and DKK-1 levels were independent risk factors for osteoporosis (all P<0.05) . Conclusion:Serum SOST and DKK-1 levels are independent risk factors for the formation of osteoporosis, which are significantly positively correlated with bone metabolism indexes PINP, BALP, and β-CTX in patients with osteoporosis after differentiated thyroid cancer surgery.

Efficacy of surgical comprehensive therapy for 456 cases of hypopharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To retrospectively analyse the efficacy of surgerical comprehensive treatment for hypopharyngeal cancer. Methods: Four hundred and fifty-six cases of hypopharyngeal squamous cell carcinoma treated from Jan 2014 to Dec 2019 were analyzed retrospectively, including 432 males and 24 females, aged 37-82 years old. There were 328 cases of pyriform sinus carcinoma, 88 cases of posterior pharyngeal wall carcinoma, and 40 cases of postcricoid carcinoma. According to American Joint Committe on Cancer(AJCC) 2018 criteria, 420 cases were of stage Ⅲ or Ⅳ; 325 cases were of T3 or T4 stage. Treatment methods included surgery alone in 84 cases, preoperative planned radiotherapy plus surgery in 49 cases, surgery plus adjuvant radiotherapy or concurrent chemoradiotherapy in 314 cases, and inductive chemotherapy plus surgery and adjuvant radiotherapy in 9 cases. The primary tumor resection methods included transoral laser surgery in 5 cases, partial laryngopharyngectomy in 74 cases, of them 48 cases (64.9%) presented with supracricoid hemilaryngopharyngectomy, total laryngectomy with patial pharyngectomy in 90 cases, total laryngopharyngectomy or with cervical esophagectomy in 226 cases, and total laryngopharyngectomy with total esophagectomy in 61 cases. Among 456 cases, 226 cases received reconstruction surgery with free jejunum transplantation, 61 cases with gastric pull-up, and 32 cases with pectoralis myocutaneous flaps. All patients underwent retropharyngeal lymph node dissection, and high-definition gastroscopy was performed during admission and follow-up. SPSS 24.0 software was used to analyze the data. Results: The 3-year and 5-year overall survival rates were respectively 59.8%, and 49.5%. The 3-year and 5-year disease specific survival rates were respectively 69.0% and 58.8%. Total metastasis rate of retropharyngeal lymph nodes was 12.7%. A total of 132 patients (28.9%) suffered from simultaneous and metachronous multiple primary carcinoma of the hypopharynx. Multivariate Logistic regression analysis showed that T3-4 disease, cervical lymph node metastasis, retropharyngeal lymph node metastasis and postoperative adjuvant radiotherapy were independent factors affecting the prognosis of patients (all P<0.05). As of April 30, 2022, a total of 221 patients died during follow-up, of 109 (49.3%) with distant metastases, which were the main cause of death. Conclusions: The efficacy of comprehensive treatment for hypopharyngeal cancer can be improved by accurate preoperative evaluation, improved surgical resection, active retropharyngeal lymph node dissection and full process intervention of the second primary cancer.

Construction of a Prognostic Model of Multiple Myeloma Based on Metabolism-Related Genes / 中国实验血液学杂志

OBJECTIVE@#To screen the prognostic biomarkers of metabolic genes in patients with multiple myeloma (MM), and construct a prognostic model of metabolic genes.@*METHODS@#The histological database related to MM patients was searched. Data from MM patients and healthy controls with complete clinical information were selected for analysis.The second generation sequencing data and clinical information of bone marrow tissue of MM patients and healthy controls were collected from human protein atlas (HPA) and multiple myeloma research foundation (MMRF) databases. The gene set of metabolism-related pathways was extracted from Molecular Signatures Database (MSigDB) by Perl language. The biomarkers related to MM metabolism were screened by difference analysis, univariate Cox risk regression analysis and LASSO regression analysis, and the risk prognostic model and Nomogram were constructed. Risk curve and survival curve were used to verify the grouping effect of the model. Gene set enrichment analysis (GSEA) was used to study the difference of biological pathway enrichment between high risk group and low risk group. Multivariate Cox risk regression analysis was used to verify the independent prognostic ability of risk score.@*RESULTS@#A total of 8 mRNAs which were significantly related to the survival and prognosis of MM patients were obtained (P<0.01). As molecular markers, MM patients could be divided into high-risk group and low-risk group. Survival curve and risk curve showed that the overall survival time of patients in the low-risk group was significantly better than that in the high risk group (P<0.001). GSEA results showed that signal pathways related to basic metabolism, cell differentiation and cell cycle were significantly enriched in the high-risk group, while ribosome and N polysaccharide biosynthesis signaling pathway were more enriched in the low-risk group. Multivariate Cox regression analysis showed that the risk score composed of the eight metabolism-related genes could be used as an independent risk factor for the prognosis of MM patients, and receiver operating characteristic curve (ROC) showed that the molecular signatures of metabolism-related genes had the best predictive effect.@*CONCLUSION@#Metabolism-related pathways play an important role in the pathogenesis and prognosis of patients with MM. The clinical significance of the risk assessment model for patients with MM constructed based on eight metabolism-related core genes needs to be confirmed by further clinical studies.

Experimental study on the toxicokinetics and gastrointestinal damage in rats poisoned with acute diquat poisoning at different exposure doses / 中华危重病急救医学

OBJECTIVE@#To observe the toxicokinetic parameters, absorption characteristics and pathomorphological damage in different parts of the gastrointestinal tract of rats poisoned with different doses of diquat (DQ).@*METHODS@#Ninety-six healthy male Wistar rats were randomly divided into a control group (six rats) and low (115.5 mg/kg), medium (231.0 mg/kg) and high (346.5 mg/kg) dose DQ poisoning groups (thirty rats in each dose group), and then the poisoning groups were randomly divided into 5 subgroups according to the time after exposure (15 minutes and 1, 3, 12, 36 hours; six rats in each subgroup). All rats in the exposure groups were given a single dose of DQ by gavage. Rats in the control group was given the same amount of saline by gavage. The general condition of the rats was recorded. Blood was collected from the inner canthus of the eye at 3 time points in each subgroup, and rats were sacrificed after the third blood collection to obtain gastrointestinal specimens. DQ concentrations in plasma and tissues were determined by ultra-high performance liquid chromatography and mass spectrometry (UPHLC-MS), and the toxic concentration-time curves were plotted to calculate the toxicokinetic parameters; the morphological structure of the intestine was observed under light microscopy, and the villi height and crypt depth were determined and the ratio (V/C) was calculated.@*RESULTS@#DQ was detected in the plasma of the rats in the low, medium and high dose groups 5 minutes after exposure. The time to maximum plasma concentration (Tmax) was (0.85±0.22), (0.75±0.25) and (0.25±0.00) hours, respectively. The trend of plasma DQ concentration over time was similar in the three dose groups, but the plasma DQ concentration increased again at 36 hours in the high dose group. In terms of DQ concentration in gastrointestinal tissues, the highest concentrations of DQ were found in the stomach and small intestine from 15 minutes to 1 hour and in the colon at 3 hours. By 36 hours after poisoning, the concentrations of DQ in all parts of the stomach and intestine in the low and medium dose groups had decreased to lower levels. Gastrointestinal tissue (except jejunum) DQ concentrations in the high dose group tended to increase from 12 hours. Higher doses of DQ were still detectable [gastric, duodenal, ileal and colonic DQ concentrations of 6 400.0 (1 232.5), 4 889.0 (6 070.5), 10 300.0 (3 565.0) and 1 835.0 (202.5) mg/kg respectively]. Light microscopic observation of morphological and histopathological changes in the intestine shows that acute damage to the stomach, duodenum and jejunum of rats was observed 15 minutes after each dose of DQ, pathological lesions were observed in the ileum and colon 1 hour after exposure, the most severe gastrointestinal injury occurred at 12 hours, significant reduction in villi height, significant increase in crypt depth and lowest V/C ratio in all segments of the small intestine, damage begins to diminish by 36-hour post-intoxication. At the same time, morphological and histopathological damage to the intestine of rats at all time points increased significantly with increasing doses of the toxin.@*CONCLUSIONS@#The absorption of DQ in the digestive tract is rapid, and all segments of the gastrointestinal tract may absorb DQ. The toxicokinetics of DQ-tainted rats at different times and doses have different characteristics. In terms of timing, gastrointestinal damage was seen at 15 minutes after DQ, and began to diminish at 36 hours. In terms of dose, Tmax was advanced with the increase of dose and the peak time was shorter. The damage to the digestive system of DQ is closely related to the dose and retention time of the poison exposure.

Traditional Chinese therapy in the treatment of ICU-acquired weakness: a Meta-analysis / 中华危重病急救医学

OBJECTIVE@#To systematically assess the efficacy of traditional Chinese therapy in the treatment of ICU-acquired weakness (ICU-AW).@*METHODS@#PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP were retrieved by computer and were used to collect a randomized controlled trials (RCT) of traditional Chinese therapy for ICU-AW. The retrieval time was from databases establishment to December 2021. After 2 researchers independently screened the literature, extracted data and evaluated the risk of bias included in the study, and RevMan 5.4 software was used for Meta-analysis.@*RESULTS@#334 articles were selected, totally 13 clinical studies and 982 patients were included, including 562 in the trial group and 420 in the control group. Meta-analysis results showed that traditional Chinese therapy could improve clinical efficacy of ICU-AW patients [relative risk (RR) = 1.35, 95% confidence interval (95%CI) was 1.20 to 1.52, P < 0.000 01], improve the muscle strength [Medical Research Council score (MRC score); standardized mean difference (SMD) = 1.00, 95%CI was 0.67 to 1.33, P < 0.000 01], improve daily life ability [modified Barthel index score (MBI score); SMD = 1.67, 95%CI was 1.20 to 2.14, P < 0.000 01], shorten mechanical ventilation time (SMD = -1.47, 95%CI was -1.84 to -1.09, P < 0.000 01), reduce the length of intensive care unit (ICU) stay [mean difference (MD) = -3.28, 95%CI was -3.89 to -2.68, P < 0.000 01], reduce the total hospitalization time (MD = -4.71, 95%CI was -5.90 to -3.53, P < 0.000 01), reduce tumor necrosis factor-α (TNF-α; MD = -4.55, 95%CI was -6.39 to -2.70, P < 0.000 01) and interleukin-6 (IL-6; MD = -5.07, 95%CI was -6.36 to -3.77, P < 0.000 01). There was no obvious advantage in reducing the severity of the disease [acute physiology and chronic health evaluation II (APACHE II; SMD = -0.45, 95%CI was -0.92 to 0.03, P = 0.07).@*CONCLUSIONS@#Based on the current research, traditional Chinese therapy can improve the clinical efficacy of ICU-AW, improve muscle strength and daily life ability, shorten mechanical ventilation, the length of ICU stay and total hospitalization time, reduce TNF-α and IL-6. But traditional Chinese therapy can not reduce the overall disease severity.