Effects of moderate-intensity continuous training and high-intensity interval training on obesity-related muscle atrophy in mice / 中国组织工程研究

BACKGROUND:Obesity has become a global health issue,often accompanied by complications including obesity-related muscle atrophy.While exercise has been reported to improve various obesity-related diseases,there is limited research focusing on exercise modes. OBJECTIVE:To compare the effects of moderate-intensity continuous training(MICT)and high-intensity interval training(HIIT)on obesity-related muscle atrophy in mice under the premise of the same exercise distance,providing a scientific basis for exercise interventions for obesity-related muscle atrophy. METHODS:Seventy-two male C57BL/6 mice were divided into six groups(n=12 per group):standard chow diet,standard chow diet+MICT,standard chow diet+HIIT,high-fat diet,high-fat diet+MICT,and high-fat diet+HIIT.The study evaluated the effects of 8-week treadmill training with different exercise modes on long-term high-fat diet-induced muscle atrophy by detecting muscle mass,muscle index,muscle fiber cross-sectional area,muscle lipid deposition,and the expression of muscle atrophy marker genes Murf-1 and Atrogin-1 in the gastrocnemius muscle of mice exposed to long-term high-fat diet. RESULTS AND CONCLUSION:Compared to the high-fat diet group,both MICT and HIIT improved the decrease in gastrocnemius muscle index(MICT+18.8%vs.HIIT+17.6%,not significant between the two modes),muscle fiber atrophy(MICT+15.5%vs.HIIT+13.7%,not significant between the two modes),and muscle lipid deposition(MICT-19.8%vs.HIIT-17.1%,not significant between the two modes).At the gene level,compared with the high-fat diet group,both MICT and HIIT could significantly down-regulate the expression of Murf-1(MICT-62.4%vs.HIIT-52.6%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01)and Atrogin-1(MICT-43.3%vs.HIIT-29.8%,the down-regulation caused by MICT was significantly greater than that by HIIT;P＜0.01).Based on exercise mode comfort and genetic evidence,MICT mode might be more suitable for exercise interventions in obesity-related muscle atrophy.

Functional and related research progress of γ-glutamyltransferase 1 / 中国医师杂志

Gamma glutamyltransferase 1 (GGT1) is involved in regulating processes such as redox, cell proliferation, tumor metastasis, and drug resistance, and is abnormally expressed in various tumors such as prostate cancer and clear cell renal cell carcinoma. This article summarizes the expression and role of GGT1 in various diseases, providing new ideas for further exploration of treatment strategies for GGT1 related diseases.

Gut microbiota and immune mechanism of type 1 diabetes mellitus / 中华内分泌代谢杂志

Type 1 diabetes mellitus is a T-cell-mediated autoimmune disease that commonly affects adolescents, characterized by progressive destruction of pancreatic β-cells, absolute insulin deficiency, and hyperglycemia. The pathogenesis of type 1 diabetes mellitus is complex and is believed to be mainly associated with immunity, environment, and genetics. There is increasing evidence that gut microbiota is closely related to the occurrence of type 1 diabetes mellitus. This article focuses on the immune mechanisms and roles of gut microbiota and its derivatives in the development of type 1 diabetes mellitus from the perspectives of innate and adaptive immunity. Additionally, it introduces therapeutic approaches targeting gut microbiota for the treatment of type 1 diabetes mellitus.

Multimorbidity status and risk factors among adults aged 45-64 years in 15 provinces of China in 2018: Based on association rule analysis / 环境与职业医学

Background Multimorbidity imposes a heavy burden on individuals, families, and society. There are relatively few studies exploring patterns of multimorbidity among middle-aged adults in China. Objective To explore the current status of multimorbidity, associated risk factors, and multimorbidity patterns among adults aged 45-64 years in China, so as to provide a scientific basis to prevent and control multimorbidity in China. Methods A total of 5494 adults aged 45-64 years from the Chinese Health and Nutrition Survey (CHNS) in 2018 were selected. Of these, 2494 (45.39%) were men and 3000 (54.61%) were women. The nine diseases included were hypertension, diabetes, dyslipidaemia, obesity, mild cognitive impairment (MCI), myocardial infarction, stroke, asthma, and tumor. The prevalence of each disease or multimorbidity was expressed as N (%). Comparisons of multimorbidity prevalence between different groups were performed using the χ2 test or Cochran-Armitage trend test. Association rule with the Apriori algorithm was used to explore the pattern of multimorbidity, with parameters set at a minimum conditional support of 3.00%, a minimum rule confidence of 50.00%, and a lift of >1.20. Logistic regression was used to evaluate the associations between selected risk factors and multimorbidity. Results In 2018, 37.44% of participants reported multimorbidity in 15 provinces of China. The prevalence of diseases in descending order was dyslipidaemia (39.99%), hypertension (39.48%), obesity (16.42%), MCI (14.47%), diabetes (14.16%), tumor (1.09%), stroke (1.04%), myocardial infarction (0.71%), and asthma (0.64%). A total of seven multimorbidity patterns were identified in this group. Obesity paired with hypertension, and diabetes paired with dyslipidemia were the two major patterns of multimorbidity in the general population and age or sex subgroups. The multimorbidity patterns of different populations were concentrated in the combination of obesity, hypertension, diabetes, and dyslipidemia. The risk of multimorbidity was lower in females than in males (OR=0.85, 95%CI: 0.75, 0.97). The multimorbidity risk was 1.56 times higher in the 55-64 years group than in the 45-54 years group (OR=1.56, 95%CI: 1.40, 1.75). Drinking in the past year increased the risk of multimorbidity by 25% (OR=1.25, 95%CI: 1.08, 1.45) compared to no alcohol comsumption in the past year. High and medium levels of physical activity were associated with a decreased OR (high: OR=0.74, 95%CI: 0.65, 0.85; medium: OR=0.81, 95%CI: 0.70, 0.93) with low level of physical activity as reference. Conclusion In 2018, there was a high prevalence rate of multimorbidity among middle-aged adults in China. The main multimorbidity patterns were obesity-hypertension and diabetes-dyslipidemia. Surveillance and interventions should be strengthened particularly for men, individuals with alcohol consumption or insufficient physical activity, and those with major multimorbidity patterns.

Gut microbiota and cerebral vessel diseases / 国际脑血管病杂志

Gut microbiota is involved in maintaining intestinal homeostasis. The bidirectional communication between intestinal flora and brain can also be conducted through the neuro-immune-endocrine network, namely, the "microbiota-gut-brain axis". A number of studies have shown that the "microbiota-gut-brain axis" disorder plays an important role in the occurrence, development and prognosis of some cerebrovascular diseases, such as cerebral small vessel disease and stroke. This article introduces the latest research progress of the relationship between gut microbiota and cerebrovascular diseases, so as to provide more ideas and options for the treatment of cerebrovascular diseases.

Application of body surface markers localization in totally implantable venous access port implantation via internal jugular vein approach / 国际外科学杂志

Objective:To investigate the feasibility of using body surface marker localization method to determine the correct position of catheter tip (lower 1/3 of the superior vena cava or the junction of superior vena cava and right atrium) in totally implantable venous access port (TIVAP) implantation via internal jugular vein approach.Methods:The clinical data of 220 patients who underwent TIVAP implantation in Beijing Tongren Hospital, Capital Medical University from June 2019 to June 2021 were retrospectively analyzed. Among them, 168 patients used the internal jugular vein approach. According to the method implemented for determining the length of central venous catheter (CVC) during the operation, the patients were divided into two groups: 136 patients using the body surface marker localization method were defined as the study group; and the remaining 32 cases treated by the intraoperative X-ray fluoroscopic localization method were defined as the control group. The difference in the excellent or good rate of CVC tip position immediately after implantation and the time of implantation was compared between the two groups. In addition, the correlation between the length of CVC indwelling, height, age, and the distance between the catheter tip and tracheal carina was analyzed for the patients with right and left internal jugular vein catheterization. Kolmogorov-Smirnov test was used for statistical distribution of measurement data. Normal distribution of measurement data was expressed as mean ± standard deviation ( ± s), independent sample t-test was used for comparison between groups. Chi-square test was used for comparison between counting data. With TIVAP catheter indenture length as dependent variable and height as independent variable, Pearson correlation analysis was performed, the relationship equation between ideal catheter indenture length and patient height was analyzed by unitary linear regression. Results:When the CVC tip was located at the second intercostal space, the third sternocostal joint and the third intercostal space, the corresponding probability of being in the correct position was 34.8%, 83.3% and 95.0% respectively. The third sternocostal joint or the third intercostal space had a higher probability of correct CVC tip location than the second intercostal space, and the difference were statistically significant ( P<0.001). Furthermore, there was no significant difference in the possibility of the CVC tip located in the correct position between the third sternocostal joint and the third intercostal space ( P=0.149). Compared with the control group (before adjusting catheter position), the proportion of excellent or good CVC position in the study group was significantly improved (94.1% vs 46.9%), and the difference was statistically significant ( χ2=41.99, P<0.001); while the total operation time was significantly shortened [(33.04±6.69) min vs (42.50±5.54) min], and the difference was statistically significant ( P<0.05). There was a linear correlation between the length of CVC insertion and height. Indwelling catheter length via right internal jugular vein approach (cm) =0.159× height (cm)-1.284 ( r=0.597, r2=0.356, P<0.001); length of catheter indwelling through the left approach (cm) =0.097× height (cm) + 12.139 ( r=0.322, r2=0.104, P=0.020). Conclusions:The third sternocostal joint or the third intercostal space would be the corresponding correct surface landmark of the CVC tip when the body surface marker localization method was adopted during the TIVAP implantation via the internal jugular vein approach. Compared with the intraoperative X-ray fluoroscopy localization, the operation time is significantly shortened with the application of the body surface marker localization method. This technique is simple and easy to master and has high reliability in determining the length of catheter and the position of CVC tip.

Embryonic stem cell pluripotent factor NANOG mediates the activity and invasion of breast cancer cells via AMPK/mTOR pathway / 中华内分泌外科杂志

Objective:To investigate the role of embryonic stem cell pluripotent factor NANOG in mediating the activity and invasion of breast cancer cells via AMPK/mTOR pathway.Methods:A total of 58 breast cancer patients were collected from Jul. 2019 to Aug. 2020, and the clinical data of each patient at admission were collected for comparative analysis. qRT-PCR was used to detect the expression level of NANOG in adjacent tissues and cancer tissues, and Western blot was used to verify the regulation of AMPK/mTOR pathway by NANOG. Cells were treated with NANOG specific plasmid or AMPK inhibitor Compound C. Cell viability was detected by MTT and invasion ability was detected by Transwell.Results:The expression of NANOG was increased in breast cancer tissues (adjacent to cancer tissue: 1.00±0.31, cancer tissue: 1.45±0.27, t=8.34, P<0.004) and cell lines (MCF-10A: 1.00±0.12, BT474: 2.64±0.25, t=10.24, P=0.001; MCF-7: 1.56±0.13, t=5.48, P=0.005; ZR-75-30:1.84±0.16, t=7.28, P=0.002), which could be used as a specific biomolecule for predicting breast cancer (all P<0.05). The expression level of NANOG may be related to lymph node metastasis, histological grade and pathological type. Compared with patients with non-lymph node metastasis (1.36±0.23) or non-invasive patients (1.35±0.25), patients with lymph node metastasis (1.54±0.27, t=2.61, P=0.012) or invasive patients (1.53±0.26, t=2.60, P=0.012) had higher expression of NANOG. After NANOG knockdown, AMPK protein and phosphorylation levels were increased, while mTOR and p70S6K protein and phosphorylation levels were decreased (all P<0.05). Knockdown of NANOG in cells inhibited the activity and invasion of breast cancer cells (activity: si-RNA: 100±8.65, si-NANOG: 58.36±4.58, t=7.37, P=0.002; invasion: si-RNA: 121.41±10.34, si-NANOG: 58.34±8.41, t=8.20, P=0.001), and the effect of knockdown of NANOG was relieved after AMPK inhibitor was used in cells (all P<0.05) . Conclusions:Embryonic stem cell pluripotent factor NANOG promotes the activity and invasion of breast cancer cells by inhibiting the activation of AMPK/mTOR pathway. NANOG can be used as an effective biomolecule for predicting breast cancer.

Clinical efficacy of TACE combined with PVE versus percutaneous microwave ablation liver partition with PVE for planned hepatectomy for hepatocellular carcinoma with insufficient remnant liver volume / 中华肝胆外科杂志

Objective:To evaluate the safety and clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with portal vein embolization (PVE) and percutaneous microwave ablation liver partition with PVE for planned hepatectomy in patients with hepatocellular carcinoma (HCC) with insu-fficient remnant liver volume.Methods:The clinical data of 51 patients with initially unresectable HCC due to insufficient remnant liver volume admitted to Zhejiang Provincial Tongde Hospital and Zhejiang Provincial People’s Hospital from January 2014 to December 2021 were retrospectively analyzed, including 37 males and 14 females, aged (56.7±11.2) years old. Patients were divided into two groups according to the treatment prior to hepatectomy: percutaneous microwave ablation liver partition combined with PVE (AP group, n=12) and TACE with PVE (TP group, n=39). Patients who successfully underwent planned hepatectomy in the above two groups were marked as resectable AP group ( n=10) and the resectable TP group ( n=29), respectively. Clinical data including the waiting time for surgery and the incidence of complications were analyzed. Patients were followed up by telephone or outpatient review. Kaplan-Meier and log-rank analysis were used for survival comparison. Results:The FLR growth rate was higher in AP group [76.5% (65.3%, 81.6%)] than that in TP group [31.4% (28.2%, 41.9%), P<0.01]. The waiting time for planned hepatectomy in the resectable AP group was 12.0 (11.3, 14.5) d, shorter than that in the resec-table TP group [21.0 (15.0, 29.0) d, P<0.05]. The incidence of postoperative complications was higher in the resectable AP group than that in the resectable TP group [80.0% (8/10) vs. 27.6% (8/29), P<0.05]. There was one perioperative death in the resectable AP group. The survival rate after PVE was lower in AP group than that in TP group, and the survival rate after hepatectomy was also lower in the resectable AP group than that in the resectable TP group (all P<0.05). Conclusion:For HCC patients with insufficient FLR, TACE combined with PVE is a safe and effective method for enlargement of liver remnant, whereas percutaneous microwave ablation liver partition with PVE showed a poor prognosis, despite the higher rate of FLR enlargement and shortened the waiting time for planned hepatectomy.

Inflammatory Bowel Disease and Neurodegenerative Diseases

A growing body of evidence has demonstrated an intricate association between inflammatory bowel disease (IBD) and neurodegenerative conditions, expanding beyond previous foci of comorbidities between IBD and mood disorders. These new discoveries stem from an improved understanding of the gut-microbiome-brain axis: specifically, the ability of the intestinal microbiota to modulate inflammation and regulate neuromodulatory compounds. Clinical retrospective studies incorporating large sample sizes and population-based cohorts have demonstrated and confirmed the relevance of IBD and chronic neurodegeneration in clinical medicine. In this review, we expound upon the current knowledge on the gut-microbiome-brain axis, highlighting several plausible mechanisms linking IBD with neurodegeneration. We also summarize the known associations between IBD with Parkinson disease, Alzheimer disease, vascular dementia and ischemic stroke, and multiple sclerosis in a clinical context. Finally, we discuss the implications of an improved understanding of the gut-microbiome-brain axis in preventing, diagnosing, and managing neurodegeneration among IBD and non-IBD patients.

Clinical Observation of Venetoclax Combined with Demethylating Agents on the Treatment of Relapsed/Refractory Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML).@*METHODS@#The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored.@*RESULTS@#The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients.@*CONCLUSION@#VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.

Cryo-EM structures for the Mycobacterium tuberculosis iron-loaded siderophore transporter IrtAB

The adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the canonical type IV exporter fold. Herein, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, or ATP analogue (AMP-PNP) at resolutions ranging from 2.8 to 3.5 Å. The structure of IrtAB bound ATP-Mg2+ shows a "head-to-tail" dimer of nucleotide-binding domains (NBDs), a closed amphipathic cavity within the transmembrane domains (TMDs), and a metal ion liganded to three histidine residues of IrtA in the cavity. Cryo-electron microscopy (Cryo-EM) structures and ATP hydrolysis assays show that the NBD of IrtA has a higher affinity for nucleotides and increased ATPase activity compared with IrtB. Moreover, the metal ion located in the TM region of IrtA is critical for the stabilization of the conformation of IrtAB during the transport cycle. This study provides a structural basis to explain the ATP-driven conformational changes that occur in IrtAB.

Value of brain functional connectivity density in differentially diagnosing different motor subtypes of Parkinson's disease and its correlation with clinical symptom scores / 中华神经医学杂志

Objective:To investigate the value of brain functional connectivity density (FCD) derived from resting-state functional magnetic resonance imaging (rs-fMRI) in differentially diagnosing 2 subtypes of Parkinson's disease (PD): tremor dominant (TD) and non-tremor dominant (nTD), as well as its correlation with clinical symptom scores.Methods:A retrospective analysis was performed; 45 PD patients (25 with TD and 20 with nTD), admitted to Department of Neurology, Drum Tower Hospital Affiliated to Medical School of Nanjing University were chosen; and 24 middle-aged and elderly volunteers matched in age, gender and years of education at the same time were chosen as normal controls (NCs). The rs-fMRI data were collected and FCD map of the whole brain was computed. The FCD differences in whole brain and brain regions enjoying different FCD were compared among the 3 groups. ROC curve was used to analyze the differential diagnostic efficacy of FCD in brain regions enjoying different FCD in TD and nTD. Correlations of FCD in brain regions enjoying different FCD with disease course, Hoehn-Yahr (H-Y) grading, unified Parkinson's disease rating scale (UPDRS) III scores, tremor scores and non-tremor scores were analyzed by Pearson or Spearman correlation analyses.Results:Brain regions enjoying different FCD among the TD, nTD, and NC groups were the right lingual gyrus, right orbital medial frontal gyrus, right insula, left superior temporal gyrus, left insula, right anterior central gyrus, left posterior central gyrus, right medial and paracingulate gyrus, and left angular gyrus. FCD in the right orbital medial frontal gyrus and left angular gyrus of TD group was significantly higher than that in the nTD group ( P<0.05); while FCD in the right insula, right anterior central gyrus, left posterior central gyrus and right medial and paracingulate gyrus of TD group was significantly lower than that in the nTD group ( P<0.05). Area under the curve of combined application of FCD in brain regions enjoying different FCD in differentially diagnosing TD and nTD was 0.842, with sensitivity and specificity of 80.0%. FCD in the left superior temporal gyrus and left posterior central gyrus was positively correlated with H-Y grading ( P<0.05), while FCD in the left angular gyrus was negatively correlated with H-Y grading ( P<0.05). FCD in the left superior temporal gyrus was positively correlated with UPDRS III scores ( P<0.05). FCD in the right lingual gyrus, right insula, left insula, right anterior central gyrus, left posterior central gyrus, right medial and paracingulate gyrus was negatively correlated with tremor scores ( P<0.05). FCD in the left superior temporal gyrus, right medial and paracingulate gyrus was positively correlated with non-tremor scores ( P<0.05), whereas that in the left angular gyrus was negatively correlated with non-tremor scores ( P<0.05). Conclusion:Abnormalities in FCD exist in certain brain regions of PD patients, with disparities between TD and nTD. Combined application of FCD in brain regions enjoying different FCD can effectively differentiate TD and nTD, and this FCD is also partially correlated with the symptom scores of PD patients.

Impacts of cadmium on mouse neural stem cells based on dose-response metabomics / 环境与职业医学

Background Cadmium (Cd) is a ubiquitous and toxic heavy metal that can accumulate in human body. Previous studies have shown that Cd exposure can induce neurotoxicity, but the underlying mechanism remains unclear. Objective To investigate the metabolic impacts of multiple doses of Cd on mouse neural stem cells (NSCs), and to explore the potential mechanism and biomarkers of its neurotoxicity. Methods The NSCs were obtained from the subventricular zone (SVZ) of 1-day-old neonatal C57BL/6 mice. The passage 3 (P3) NSCs were exposed to CdCl2 at designed doses (0, 0.5, 1.0, and 1.5 μmol·L−1). The cells were treated with seven replicates, of which one plate was for cell counting. After 24 h of exposure, the intracellular and extracellular metabolites were extracted respectively and then detected by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS). The orthogonal partial least-squares discriminant analysis (OPLS-DA) was applied to visualize the alterations of metabolomic profiles and to identify the differential metabolites (DMs) based on their variable importance for the projection (VIP) value >1 and P<0.05. The metabolite set enrichment analysis (MSEA) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were performed to recognize the significantly altered metabolite sets and pathways. The dose-response relationships were established and the potential biomarkers of Cd exposure were identified by 10% up-regulated or 10% down-regulated effective concentration (EC) of target metabolites. Results A total of 1201 metabolites were identified in the intracellular metabolomic samples and 1207 for the extracellular metabolomic samples. The intracellular and extracellular metabolome of Cd-treated NSCs were distinct from that of the control group, and the difference grew more distant as the Cd dosage increased. At 0.5, 1.0, and 1.5 μmol·L−1 dosage of Cd, 87, 83, and 185 intracellular DMs and 161, 176, and 166 extracellular DMs were identified, respectively. Within the significantly changed metabolites among the four groups, 176 intracellular DMs and 167 extracellular DMs were identified. Both intracellular and extracellular DMs were enriched in multiple lipid metabolite sets. Intracellular DMs were mainly enriched in taurine and hypotaurine metabolism, glycerophospholipid metabolism, and glycerolipid metabolism pathways. Extracellular DMs changed by Cd were mainly enriched in glycerophospholipid metabolism, steroid hormone biosynthesis, and cysteine and methionine metabolism pathways. Among intracellular DMs, 125 metabolites were fitted with dose-response relationships, of which 108 metabolites showed linear changes with the increase of Cd dosage. And 134 metabolites were fitted with dose-response relationships among extracellular DMs, of which 86 metabolites showed linear changes. The intracellular DMs with low EC values were hypotaurine, ethanolamine, phosphatidylethanolamine, and galactose, while the extracellular DMs with low EC values were acetylcholine and 1,5-anhydrosorbitol. Conclusion Cd treatment can significantly alter the intracellular and extracellular metabolome of mouse NSCs in a dose-dependent manner. The neurotoxicity of Cd may be related to glycerophospholipid metabolism. Acetylcholine, ethanolamine, and phosphatidylethanolamine involved in glycerophospholipid metabolism pathway might be potential biomarkers of Cd-induced neurotoxicity.

Evaluation of the efficacy and safety of Camrelizumab combined with Shenqi Fuzheng injection in the treatment of advanced non-squamous non-small cell lung cancer patients / 中国药师

Objective To investigate the clinical efficacy and safety of the Camrelizumab combined with Shenqi Fuzheng injection of advanced non-squamous non-small cell lung cancer(NSCLC).Methods Patients with advanced squamous NSCLC diagnosed and treated in the department of medical oncology of The First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2023 were selected as the study subjects,and all patients were treated with pemetrexed combined with carboplatin chemotherapy.On the basis of the chemotherapy regimen,patients were divided into the Camrelizumab group(treated with Carelizumab)and the Camrelizumab+SFI group(treated with Camrelizumab+SFI).The short-term and long-term efficacy were evaluated using objective response rate(ORR),disease control rate(DCR),progression free survival(PFS),and overall survival(OS).Survival data were analyzed using Kaplan-Meier method.The occurrence of side effects the adverse drug reactions was evaluated according to the common terminology standard for adverse events(CTCAE 4.03).Results A total of 95 patients with advanced NSCLC were included in this study.Among them,48 patients were in the Camrelizumab group,and 47 patients were in the Camrelizumab+SFI group.The ORR of advanced non-squamous NSCLC patients in the Camrelizumab+SFI group and Carolizumab group were 59.57％and 45.83％,respectively(x2=1.799,P=0.180),with DCR of 78.72％and 58.33％,respectively(x2=4.569,P=0.033).The median PFS(8.87 months vs.6.30 months,P=0.001 7)and median OS(9.13 months vs.7.73 months,P=0.037)of patients in the Camrelizumab+SFI group were significantly higher than those in the Camrelizumab group.In addition,there was no significant difference in the incidence of adverse reactions between two groups(P＞0.05).Conclusion Camrelizumab combined with Shenqi Fuzheng injection can improve the disease control rate and prolong the PFS and OS of patients with advanced non-squamous NSCLC.

Risk factors for clinically relevant postoperative pancreatic fistula of pancreatic tumor in children / 中华肝胆外科杂志

Objective:To analyze the influencing factors of clinically relevant postoperative pancreatic fistula (CR-POPF) in children with pancreatic tumors after surgery.Methods:The clinical data of 123 children undergoing surgery for pancreatic tumor in Beijing Children's Hospital, Capital Medical University from January 2007 to March 2020 were retrospectively analyzed, including 39 males and 84 females, with a median age of 9.8 years (6.7 to 11.8). Patients without pancreatic fistula and with biochemical leakage were included in control group ( n=95), while patients with grade B and C pancreatic fistula were divided into CR-POPF group ( n=28). The independent influencing factors of CR-POPF were analyzed by univariate and multivariate logistic regression. Results:Among 123 children, 28 cases (22.8%) developed CR-POPF, including 24 cases (85.7%, 24/28) of grade B pancreatic fistula and 4 cases (14.3%, 4/28) of grade C pancreatic fistula. There were significant differences between CR-POPF and control groups in the age > 8 years and 4 months, tumor location, operation time >390 min and procedures (all P<0.05). Multivariate logistic regression analysis showed an increased risk of CR-POPF in children aged > 8 years and 4 months ( OR=8.226, 95% CI: 1.813-37.333, P=0.006) and undergoing duodenum-preserving pancreatic head resection (DPPHR) ( OR=3.353, 95% CI: 1.282-8.767, P=0.014). Conclusion:Age>8 years and 4 months and DPPHR are independent risk factors for CR-POPF in children with pancreatic tumors after surgery.

Clinical application of 99Tc m-MIBI SPECT/CT muscle imaging in the diagnosis of dystonic muscle of spasmodic torticollis / 中华核医学与分子影像杂志

Objective:To explore the potential clinical value of 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT/CT muscle imaging in the diagnosis of cervical dystonia (CD). Methods:From January 2021 to April 2022, 50 patients with CD (14 males, 36 females; age (45.8±12.5) years) who were treated in Second Affiliated Hospital of Soochow University were prospectively included. The 99Tc m-MIBI SPECT/CT muscle imaging results of 400 pieces of muscle (bilateral sternocleidomastoid, musculus scapulae, splenius capitis and musculus trapezius; each of 100 pieces) in 50 patients were analyzed and divided into the dystonic muscle group and normal muscle group according to the electromyography (EMG). Toronto western spasmodic torticollis rating scale (TWSTRS) score, SUV max and target-to-background ratio (TBR) of single superficial cervical muscle and total cervical muscle, and EMG diagnosis results were obtained before botulinum toxin injection. ROC curves of SUV max and TBR of dystonic muscles were constructed to determine AUCs and the difference was compared by Delong test. Differences of SUV max and TBR between 2 groups were analyzed by Mann-Whitney U test. Spearman rank correlation analysis was used to analyze the correlation of SUV max, TBR and TWSTRS scores of total cervical muscle. Results:There were 205 pieces of muscle in dystonic muscle group and 195 pieces of muscle in normal muscle group. The uptake of 99Tc m-MIBI in dystonic muscle was significantly increased in CD patients, and the non-whole uptake of 99Tc m-MIBI was increased in some dystonic muscles, which was manifested as uneven uptake of the whole muscle. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of visual analysis were 95.12%(195/205), 75.90%(148/195), 85.75%(343/400), 85.58%(195/242) and 93.67%(148/158), respectively. There were significant differences of SUV max (1.74(1.42, 2.12) vs 0.92(0.81, 0.99)) and TBR (2.55(1.92, 3.27) vs 1.44(1.22, 1.73)) between the dystonic muscle group and the normal muscle group ( z value: -15.29, -12.69, both P<0.001). The diagnostic efficiency of SUV max in dystonic muscle was better than TBR (AUC: 0.942 vs 0.867; z=5.03, P<0.001). SUV max, TBR and TWSTRS score in the neck muscles of patients with CD showed positive correlation ( rs values: 0.44, 0.45, both P<0.001). Conclusion:99Tc m -MIBI SPECT/CT muscle imaging is a good diagnostic method for dystonic muscle in patients with CD.

Transrectal biopsy of prostate complicated with Fournier gangrene: a case report / 中华泌尿外科杂志

This article reports a case of Fournier gangrene after transrectal biopsy of the prostate. A 69-year-old male patient was admitted to our hospital for dysuria. The preoperative diagnosis was bladder stones and suspicious prostate cancer. During the same time, the patient underwent transurethral holmium laser lithotripsy and transrectal prostate biopsy. Fournier gangrene occurred on the second day after the operation. After active treatment such as upgraded antibiotics and debridement of the scrotum and perineum, the condition was controlled. The perineal wound healed 2 months later without secondary suture. Perioperative transurethral examination should be avoided during transrectal prostate biopsy. To avoid delayed diagnosis and treatment, it is necessary to improve the understanding of postoperative complications of Fournier's gangrene.

Comparison of effects of propofol, fospropofol disodium and sevoflurane on pulmonary metastasis after radical mastectomy for breast cancer in mice / 中华麻醉学杂志

Objective:To compare the effects of propofol, fospropofol disodium and sevoflurane on pulmonary metastasis after radical mastectomy for breast cancer in mice.Methods:SPF-grade healthy female C57 mice, aged 4-6 weeks, weighing 14-18 g, were used in this study. Eighteen mouse breast cancer models were successfully prepared by luciferase-labeled mouse 4T1 breast cancer cells, and the mice were divided into 3 groups ( n=6 each) by the random number table method: sevoflurane group (S group), propofol group (P group) and fospropofol disodium group (PD group). Group S inhaled 3% sevoflurane, propofol 200 mg/kg was intraperitoneally infused in group P, and fospropofol disodium 182 mg/kg was injected via the tail vein in group PD, and anesthesia was maintained for 3 h to perform radical mastectomy in three groups. The lung metastasis of mouse breast cancer cells was evaluated by in vivo imaging at 2 weeks after surgery, and then the mice were sacrificed, and lung tissues were obtained for determination of the expression of extracellular regulatory protein kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), P38 and phosphorylated P38 (p-P38) by Western blot. Results:Compared with S group, the number of lung metastases and total number of cell metastases in breast cancer cells were significantly decreased, and the expression of p-ERK1/2 and p-P38 in lung metastases was down-regulated in P group and PD group ( P<0.05). There was no significant difference in the parameters mentioned above between P group and PD group ( P>0.05). Conclusions:Propofol and fospropofol disodium have better efficacy than sevoflurane in reducing lung metastasis after radical mastectomy, which may be related to down-regulation of p-ERK1/2 and p-P38 expression in mice.

Genetic diagnosis in two families with dystrophic epidermolysis bullosa / 中华皮肤科杂志

Objective:To analyze clinical characteristics of and causative genes in two families with dystrophic epidermolysis bullosa, and to reveal the pathogenesis of the disease and mechanisms underlying phenotypic differences between patients.Methods:DNA was extracted from peripheral blood samples of members from two families with dystrophic epidermolysis bullosa, and subjected to high-throughput sequencing and Sanger sequencing.Results:The clinical manifestations of the 2 probands in the 2 families were consistent with the diagnosis of dystrophic epidermolysis bullosa, and the symptoms of the proband in family 1 were more serious than those of other patients in the family. Genetic testing showed that all patients in family 1 carried a mutation c.6082G>C (p.G2028R) in the COL7A1 gene, and the proband and her phenotypically normal mother and uncle also carried a splice-site mutation c.7068+2 (IVS91) T>G in the COL7A1 gene, both of which were first reported. The proband in family 2 carried the mutations c.6081_6082 ins C (p.G2028Rfs*71) and c.1892G>A (p.W631X, first reported) in the COL7A1 gene, which were inherited from her father and mother, respectively.Conclusion:The two pathogenic mutations may be the molecular mechanism underlying the severe clinical phenotype in the proband in family 1; the first reported mutations enriched the mutation spectrum of the COL7A1 gene.

Correlation between triglyceride glucose index and risk of acute pancreatitis:A prospective cohort study / 实用医学杂志

Objective To investigate the correlations of triglyceride glucose index(TyG)levels at different baselines with the risk of new-onset acute pancreatitis(AP)among the workers at Kailuan Group.Methods A total of 124 516 subjects were enrolled from 2006 to 2009 and followed up by health examinations of the workers in the group.The subjects with a history of AP or incomplete information on TG and FPG data were excluded.The cumulative incidence rate was determined by Log-Rank method.Multivariate Cox proportional hazards regression model was used to calculate hazard ratios(HR)for AP related to baseline TyG level after adjusting for the effects of multiple confunding factors.Results The subjects were divided into four groups(TyG≤6.59,6.59<TyG≤6.98,6.98<TyG4≤7.46,TyG>7.46)according to the TyG levels,and the incidence of new-onset AP was observed in all the groups.For a follow-up of(12.59±0.98)years,399 cases of AP were observed.The corresponding incidence of AP in each tertile was 1.67,2.32,2.53,and 3.65 events per 10,000 person-years,respectively.After Cox analysis and correction of multiple confounding factors,the risk of AP incidence was increased in the TyG>7.46 group,with an HR of 1.94[(95%CI(1.42,2.65),P<0.01].Conclusion TyG at its baseline of above 7.46 can increase the risk of AP.