Explainable machine learning for early predicting treatment failure risk among patients with TB-diabetes comorbidity.

The present study aims to assess the treatment outcome of patients with diabetes and tuberculosis (TB-DM) at an early stage using machine learning (ML) based on electronic medical records (EMRs). A total of 429 patients were included at Chongqing Public Health Medical Center. The random-forest-based Boruta algorithm was employed to select the essential variables, and four models with a fivefold cross-validation scheme were used for modeling and model evaluation. Furthermore, we adopted SHapley additive explanations to interpret results from the tree-based model. 9 features out of 69 candidate features were chosen as predictors. Among these predictors, the type of resistance was the most important feature, followed by activated partial throm-boplastic time (APTT), thrombin time (TT), platelet distribution width (PDW), and prothrombin time (PT). All the models we established performed above an AUC 0.7 with good predictive performance. XGBoost, the optimal performing model, predicts the risk of treatment failure in the test set with an AUC 0.9281. This study suggests that machine learning approach (XGBoost) presented in this study identifies patients with TB-DM at higher risk of treatment failure at an early stage based on EMRs. The application of a convenient and economy EMRs based on machine learning provides new insight into TB-DM treatment strategies in low and middle-income countries.

Mycobacterium vaccae alleviates allergic airway inflammation and airway hyper-responsiveness in asthmatic mice by altering intestinal microbiota.

Host immunity can influence the composition of the gut microbiota and consequently affect disease progression. Previously, we reported that a Mycobacterium vaccae vaccine could ameliorate allergic inflammation in asthmatic mice by regulating inflammatory immune processes. Here, we investigated the anti-inflammatory effects of M. vaccae on allergic asthma via gut microbiota modulation. An ovalbumin (OVA)-induced asthmatic murine model was established and treated with M. vaccae. Gut microbiota profiles were determined in 18 BALB/c mice using 16S rDNA gene sequencing and metabolomic profiling was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. Mycobacterium vaccae alleviated airway hyper-reactivity and inflammatory infiltration in mice with OVA-induced allergic asthma. The microbiota of asthmatic mice is disrupted and that this can be reversed with M. vaccae. Additionally, a total of 24 differential metabolites were screened, and the abundance of PI(14:1(9Z)/18:0), a glycerophospholipid, was found to be correlated with macrophage numbers (r = 0.52, p = 0.039). These metabolites may affect chemokine (such as macrophage chemoattractant protein-1) concentrations in the serum, and ultimately affect pulmonary macrophage recruitment. Our data demonstrated that M. vaccae might alleviate airway inflammation and hyper-responsiveness in asthmatic mice by reversing imbalances in gut microbiota. These novel mechanistic insights are expected to pave the way for novel asthma therapeutic strategies.

Non­diagnostic electromagnetic navigation bronchoscopy biopsy: Predictive factors and final diagnoses.

The present study aimed to explore the final diagnosis of pulmonary nodules with an initial non-diagnostic result on electromagnetic navigation bronchoscopy (ENB) biopsy and the predictive factors for a non-diagnostic result. A total of 198 nodules from 194 patients that were suspected to be malignant tumors were included in the present study. The initial biopsy pathology results were divided into two groups: The diagnostic group and the non-diagnostic group. The diagnostic group was defined as a successful initial biopsy to obtain a diagnosis, including malignant and benign diagnoses. The non-diagnostic group was defined as a non-specific benign diagnosis, normal lung tissue or an unsuccessful biopsy. Among the 198 nodules, 139 (70.2%) were in the diagnostic group and 59 (29.8%) were in the non-diagnostic group. Predictive factors for a non-diagnostic biopsy included nodule size ≤1.5 cm [odds ratio (OR), 2.05; 95% confidence interval (CI), 1.03-4.09], non-solid nodules (OR, 2.71; 95% CI, 1.33-5.64) and nodules in the left lung (OR, 2.50; 95% CI, 1.27-4.92). Of the 59 non-diagnostic biopsies, 46 were finally confirmed to be malignant by surgery. Notably, non-diagnostic biopsies with non-solid nodules (OR, 7.64; 95% CI, 3.11-18.76) were more likely to be malignant. In conclusion, the predictive factors for a non-diagnostic biopsy were nodule size ≤1.5 cm and non-solid nodules. It was not rare for patients to finally be diagnosed with a malignancy in the non-diagnostic group. Therefore, care should be taken when the results of an ENB are non-diagnostic to prevent misdiagnosis.

Dosage selection and effect evaluation of sodium pentobarbital in tree shrew anesthesia.

To achieve surgical anesthesia in animal experimentation, it is important to select the appropriate anesthetic dose. However, few studies have investigated the reasonable anesthetic dose in tree shrew (Tupaia belangeri). The aim of the study was to review the literature to determine the most commonly used anesthetic dose in tree shrew and to calculate the reasonable equivalent dose between tree shrew and rat based on the body surface area conversion. Two groups of 10 adult tree shrews each were anesthetized with 1% sodium pentobarbital through intraperitoneal injection separately at doses of 62 mg/kg (equivalent dose) and 40 mg/kg (reported dose). Anesthetic depth and times were assessed in addition to vital signs. The results showed that the dosage was quite different across studies, ranging from 15 mg/kg to 80 mg/kg, with 40 mg/kg being the most frequently reported dose. However, the group of tree shrews anesthetized with the commonly reported dose were unable to meet the requirements of surgery. In contrast, the equivalent dose (62 mg/kg, intraperitoneal injection with sodium pentobarbital) calculated by body surface area conversion could achieve an anesthetic time of 44.28 ± 3.95 min with no serious or fatal effects. During anesthetic monitoring, we found that sodium pentobarbital had an inhibitory effect on the blood pressure, pulse rate, respiratory rate and rectal temperature in tree shrews, especially on the respiratory rate. Thus, our study indicated that the use of the equivalent dose of sodium pentobarbital was effective in anesthetizing tree shrews.

[QMEC-based Analysis of the Soil Microbial Functional Potentials across Different Tibetan Plateau Glacier Forelands].

Soil microorganisms dominate the biogeochemical cycles of elements in glacier forelands, which continue to expand due to the climate warming. We analyzed the soil microbial functional characteristics among three types of glacier forelands on the Tibetan Plateau: Yulong Glacier (Y), a temperate glacier; Tianshan Urumqi Glacier No.1 (T), a sub-continental glacier; and Laohugou Glacier No.12 (L), a continental glacier. Here, soil microbial functional genes were quantified using quantitative microbial element cycling technology (QMEC). We found that, in the three glacier forelands, the abundances of soil microbial functional genes related to hemicellulose degradation and reductive acetyl-CoA pathway were highest compared with other carbon-related functional genes. The main nitrogen cycling genes were involved in ammonification. The functional genes of the phosphorus cycle and sulfur cycle were related to organic phosphate mineralization and sulfur oxidation. Furthermore, the soils of the temperate glacier foreland with better hydrothermal conditions had the most complex microbial functional gene structure and the highest functional potentials, followed by those of the soils of continental glacier foreland with the driest environment. These significant differences in soil microbial functional genes among the three types of glacier forelands verified the impacts of geographic difference on microbial functional characteristics, as well as providing a basis for the study of soil microbial functions and biogeochemical cycles in glacier forelands.

Study on the change of neutralizing antibody level in plasma donors after a third shot of inactivated novel coronavirus vaccine / 中国输血杂志

【Objective】 To investigate the trend of neutralizing antibody level in plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine. 【Methods】 Three commercial ELISA kits for novel coronavirus neutralization antibody detection, manufactured by Company A, B and C, were chosen and screened by Pseudotype Neutralization Test from December 2021 to June 2022. A total of 410 plasma samples from 64 plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine and there after donated plasma within six months were detected by the selected ELISA kit from July to October, 2022. The data were analyzed by Excel 2013 and SPSS 26 software. 【Results】 The high-throughput ELISA kit for SARS-CoV-2 neutralizing antibody detection, manufactured by Company A, was selected for further antibody titer detection. The mixed plasma titers were 1 337.34, 1 148.89, 852.19, 681.38, 556.44 and 457.19 U/mL from 1 to 6 months, respectively, after the 3rd shot of vaccine. The neutralizing antibody titer level began to increase around 7 days after the 3rd shot of vaccine injection and peaked (peak range: 264.07-2 208.39 U/mL, median: 569.34 U/mL) at 1 month (range: 9-43 days, median: 22 days), and then gradually decreased (P<0.05). 【Conclusion】 The neutralizing antibody titer of plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine began to rise around 7 days after vaccination, which reached the peak value at around 1 month and then gradually decreased.

Selection of sterilizing-grade filter for preparation of human coagulation factor Ⅷ/ von Willebrand factor complex / 中国输血杂志

【Objective】 To screen the sterilizing-grade filters applicable for production of human coagulation factor Ⅷ/von Willebrand factor complex(FⅧ/VWF)and study the sterilization filtration process. 【Methods】 Four sterilizing-grade filters for FⅧ/VWF were evaluated through indicators such as filtration capacity, filtration flux, recovery rate of FⅧ activity, recovery rate of VWF activity, recovery rate of VWF antigen, recovery rate of protein and VWF molecular distribution. The sterilizing-grade filter with the best filtration performance was selected for further study. The study was designed by general full-factor design to determine the appropriate filitered protein concentration and filitered speed range through evaluating the total filtered protein amount, recovery rate of protein and filtration efficiency, and then the process operation parameters was determined. 【Results】 The filtration flux of Sartobran P, Sartopore 2 XLG, Sartopore Platinum and Sartopore 2 XLI were 1.71±0.01, 1.80±0.01, 1.34±0.01, and 1.81±0.04 L·(m2)-1·min-1, respectively; the recovery rates (%) of FⅧ activity were 97.09±2.82, 99.22±0.99, 96.87±1.85 and 93.76±1.21, respectively; the recovery rates (%) of VWF activity were 98.12±1.42, 99.95±1.85, 94.80±1.62 and 92.09±1.67, respectively. Between Sartopore 2 XLG and Sartobran P, the difference of filtration flux (P<0.001) was statistically significant; between Sartopore 2 XLG and Sartopore Platinum, the differences of the filtration flux (P<0.001) and VWF potency recovery rate (P<0.05) were statistically significant; between Sartopore 2 XLG and Sartopore 2 XLI, the differences of FⅧ potency recovery rate (P<0.01) and VWF potency recovery rate (P<0.01) were statistically significant. The optimal process operating space of Sartopore 2 XLG was protein concentration of 0.45-0.58 mg/mL, and filtration rate of 1.48-2.95 L·(m2)-1·min-1. 【Conclusion】 Sartopore 2 XLG is the most suitable filter for the production of FⅧ/VWF and the DoE test proves that it has good process operation space.

Subxiphoid and subcostal arch thoracoscopic versus median sternotomy enlarged thymectomy for the treatment of myasthenia gravis complicated with thymoma: A propensity score matching study / 中国胸心血管外科临床杂志

@#Objective    To compare clinical effects of enlarged thymectomy for the treatment of myasthenia gravis (MG) complicated with thymoma via subxiphoid and subcostal arch thoracoscopic resection versus median sternotomy resection. Methods    We retrospectively analyzed the clinical data of patients with MG complicated with thymoma admitted in Tangdu Hospital of the Air Force Military Medical University between December 2011 and December 2021. Patients who underwent subxiphoid and subcostal arch thoracoscopic enlarged thymectomy were allocated to a SR group, and patients who underwent median sternotomy enlarged thymectomy were allocated to a MR group. Perioperative outcomes were compared between the two groups. Results    A total of 456 patients were collected. There were 51 patients in the MR group, including 30 males and 21 females aged 23-66 (49.5±11.8) years. There were 405 patients in the SR group, among whom 51 patients were matched to the MR group by propensity score matching, including 28 males and 23 females aged 26-70 (47.2±12.2) years. The operations were accomplished successfully in all patients, and no conversion to thoracotomy occurred in the SR group. The SR group had advantages in the operation time, intraoperative blood loss,  chest drainage duration, hospital stay time, patients’ satisfaction level, pain score and complications (all P<0.05). No statistical difference was found in the number of intraoperative lymph node dissection stations, number of intraoperative lymph nodes dissected or remission of MG between the two groups (P>0.05). Conclusion    Subxiphoid and subcostal arch thoracoscopic enlarged thymectomy and lymphadenectomy is a safe, effective and feasible minimally invasive procedure for the treatment of MG complicated with thymoma.

Guiding role of three-dimensional simulation modeling technology in laparoscopic-assisted radical resection of rectal cancer / 国际外科学杂志

Objective:Three-dimensional simulation modeling technology was used to conduct three-dimensional reconstruction, classification and measurement for the anatomic structures of colorectal canal, tumor and key blood vessels in patients with rectal cancer before operation. And the accuracy of the data and information obtained for the prediction of anastomotic tension, important types of vascular variant, positioning of anatomical landmarks, etc. in laparoscopic-assisted radical resection of rectal cancer, and the guiding effect of operation was evaluated.Methods:The clinical data of 50 patients with laparoscopic-assisted radical resection of rectal cancer treated in the General Surgery Department, Beijing Ditan Hospital Capital Medical University from January 2019 to February 2021 were analyzed retrospectively, including 31 males and 19 females, aged from 42 to 83 years old, with an average age of (62.72 ±15.21) years. The patients were divided into two groups according to whether the patients underwent three-dimensional simulation reconstruction before operation. The patients who underwent abdomen pelvic enhancement CT and further three-dimensional reconstruction before surgery were taken as reconstruction group ( n=24), and the patients who were only routinely performed abdomen pelvic enhancement CT before operation were taken as control group ( n=26). For the patients in the reconstruction group, the CT images were modeled by Mimics software before operation, and the key data such as the length of colorectal and tumor, the correlation length of rigid structure of pelvic wall, the length of inferior mesenteric artery (IMA) from the bifurcation point of left and right arteria iliaca communis, the type and proportion of IMA variation, the length of left colonic artery (LCA) from the beginning of IMA and the distance between LCA and IMV were measured, and the consistency correlation coefficient (CCC) was analyzed with the actual data obtained during operation. And then the accuracy of three-dimensional simulation modeling technology for surgical guidance was evaluated. MedCalc 19.0 software was used for statistical analysis. Results:In the reconstruction group, regarding the data of each dimension of the model (intestinal tract, pelvic cavity, blood vessels) and the corresponding structural measurements during the operation, the consistent correlation coefficient (CCC) evaluation was more than 0.9. One case was predicted to have free splenic flexure of colon and one case actually had free splenic flexure of colon. The prediction accuracy was 100%. The IMA variants in the reconstruction group were divided into 4 types, all of which were verified by operation. Compared with the control group, the operation time ( P=0.011) and the location time (IMA, P=0.043; LCA, P=0.007; IMV, P=0.034) of each vessel in the reconstruction group were shorter, and the amount of intraoperative blood loss was less ( P=0.017). Conclusion:The application of three-dimensional simulation modeling technology before operation is helpful for the operator to accurately predict the intraoperative anastomotic tension, the type of IMA variation and the related diameter length, based on which the accurate operation plan can be made to guide the operation.

Progress of Different Programmed Cell Death Pathways in Kidney Cancer / 肿瘤防治研究

Programmed cell death (PCD) is a genetically determined, active and orderly cell death in the organism, and it affects the evolution of the organism, maintenance of its homeostasis, and development of several tissues and organs. The abnormal regulation of this process is closely related to various human diseases, including cancer. The identified pathways of PCD include apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis, which can be activated when cells are stimulated by various internal and external environmental factors. These pathways can induce cell death or maintain cell survival in kidney cancer cells under the regulation of various signaling molecules, thus affecting tumor progression or therapeutic efficacy. In this paper, the role of these PCD pathways in the development of kidney cancer was reviewed in light of recent research advances to provide new directions for the in-depth study of the pathogenesis of kidney cancer and the development of targeted antitumor drugs.

Analysis of KIF1A gene variant in a Chinese pedigree affected with Spastic paraplegia type 30 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with hereditary spastic paraplegia type 30 (HSP30).@*METHODS@#A proband presented at the Second Hospital of Shanxi Medical University in August 2021 was selected as the study subject. The proband was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The proband was found to have harbored a heterozygous c.110T>C variant in exon 3 of the KIF1A gene, which can cause substitution of isoleucine by threonine at position 37 (p.I37T) and alter the function of its protein product. The same variant was not found in his parents, elder brother and elder sister, suggesting that it has a de novo origin. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PM2_Supporting+PP3+PS2).@*CONCLUSION@#The c.110T>C variant of the KIF1A gene probably underlay the HSP30 in the proband. Above finding has enable genetic counseling for this family.

Association Between Promoter Methylation of Vitamin D Metabolic Pathway Genes and Tuberculosis and Diabetes Comorbidity in a Chinese Han Population: A Case-Control Study.

Background: Deficiency vitamin D and hyperglycemia could be related to weakened innate immune response and aggravate the progression of tuberculosis (TB). This study hypothesized that DNA promoter methylation of the pivotal genes in the vitamin D metabolic pathway might be related to diabetes and tuberculosis co-morbidity (TB-DM) susceptibility. Methods: A total of 50 TB-DM and 50 healthy subjects (HS) were included in the present study. Targeted bisulfite sequencing was applied to detect the methylation of the promoter regions of candidate genes in the vitamin D metabolic pathway (CYP24A1, CYP27B1, CYP2R1, DHCR7, and VDR) in whole blood. Results: The overall methylation level of candidate genes in this study was lower in patients with TB-DM than HS, except for CYP2R1. The results of the ROC demonstrated the potential of CYP24A1, CYP27B1, DHCR7, and VDR promoter methylation as a biomarker for diagnosing TB-DM, with all the AUC above 0.7. In subgroup analysis, we found that lower circulating vitamin D is related to a low level of CYP24A1, CYP27B1, and DHCR7 promoter methylation in patients with TB-DM. With decreasing methylation level, risk of TB-DM was significantly increased (odds ratio, 95% CI 0.343, 0.144-0.821 for CYP24A1; 0.461, 0.275-0.773 for CYP27B1; 0.09, 0.015-0.530 for DHCR7; 0.006, 0.0003-0.115 for VDR). Besides, our results revealed that there was a significant correlation between DNA promoter methylation of selected genes in the vitamin D metabolic pathway and platelet indices in TB-DM. However, there was no correlation between DNA methylation of the four genes and fasting glucose and HbA1c. Conclusion: Our results could suggest that the selected genes in the vitamin D metabolic pathway may be involved in the pathological process of TB-DM, but independent of the process of hyperglycemia to impaired immune responses to Mtb.

The dynamic metabolic profile of Qi-Yu-San-Long decoction in rat urine using UPLC-QTOF-MSE coupled with a post-targeted screening strategy / 药物分析学报

Qi-Yu-San-Long decoction(QYSLD)is a traditional Chinese medicine that has been clinically used in the treatment of non-small-cell lung cancer(NSCLC)for more than 20 years.However,to date,metabolic-related studies on QYSLD have not been performed.In this study,a post-targeted screening strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight full infor-mation tandem mass spectrometry(UPLC-QTOF-MSE)was developed to identify QYSLD-related xeno-biotics in rat urine.The chemical compound database of QYSLD constituents was established from previous research,and metabolites related to these compounds were predicted in combination with their possible metabolic pathways.The metabolites were identified by extracted ion chromatograms using predicted m/z values as well as retention time,excimer ions,and fragmentation behavior.Overall,85 QYSLD-related xenobiotics(20 prototype compounds and 65 metabolites)were characterized from rat urine.The main metabolic reactions and elimination features of QYSLD included oxidation,reduction,decarboxylation,hydrolysis,demethylation,glucuronidation,sulfation,methylation,deglycosylation,acetylation,and associated combination reactions.Of the identified molecules,14 prototype compounds and 58 metabolites were slowly eliminated,thus accumulating in vivo over an extended period,while five prototypes and two metabolites were present in vivo for a short duration.Furthermore,one pro-totype and five metabolites underwent the process of"appearing-disappearing-reappearing"in vivo.Overall,the metabolic profile and characteristics of QYSLD in rat urine were determined,which is useful in elucidating the active components of the decoction in vivo,thus providing the basis for studying its mechanism of action.

Prospects for plasma protein products in China / 中国输血杂志

Plasma protein products, essential drugs for various clinical diseases, are therapeutic biological products extracted from healthy human plasma. The research and development of new plasma protein products, led by United States and European, has been widely deepened and enhanced. Therefore, accelerating the development of new plasma protein products in China is of great significance. This review summarizes the research and development of plasma protein products that have been marketed abroad but have not produced in China, as well as analyzes the difficulties and prospects of the development of plasma protein products in China.

Method for the detection of human immunoglobulin Fc function based on surface plasmon resonance: preliminary establishment and validation / 中国输血杂志

【Objective】 To establish a method for detecting human immunoglobulin Fc function based on surface plasmon resonance technology. 【Methods】 Based on the characteristic that FcγRI can be binded to the Fc segment of IgG, the affinity constant of the sample was detected by surface plasmon resonance, and its Fc function was the KD ratio of the sample to the standard. The method was validated for specificity/specificity, precision and robustness. The method and the pharmacopoeia method were used to detect the Fc function of 30 human immunoglobulins, and the correlation and consistency of the detection results were analyzed. 【Results】 The method validation results showed that this method has strong specificity/specificity (t values were 0.15, 0.22, both P>0.05), good precision (CV value 5.37%~10.69%) and good robustness (CV value 10.06%). The detection results of this method and the pharmacopoeia method have high correlation (r=0.96, P<0.05) and high consistency (Bias-2.060, 95% Limits of Agreement-5.628~1.508). 【Conclusion】 A method for detecting human immunoglobulin Fc function based on surface plasmon resonance has been successfully established.

Influence of different levels of heparin and antithrombin Ⅲ on human coagulation factor Ⅸ activity / 中国输血杂志

【Objective】 To study the effect of different concentrations of heparin, ATⅢ or a mixture of heparin and antithrombin Ⅲ (ATⅢ) (1∶1)on the activity of human coagulation factor Ⅸ (FⅨ). 【Methods】 The heparin or heparin/ATⅢ with different concentrations were added into human coagulation Ⅸ products or human prothrombin complex (PCC) to prepare heparin or heparin/ATⅢ samples, containing 0, 0.1, 0.3, 0.5, 0.8, 1, 2 and 4 IU per unit. ATⅢ with different concentrations were added into FⅨ or PCC to prepare ATⅢ samples containing ATⅢ 0, 0.1, 0.5 and 1 IU per unit. The FⅨ activity of the samples prepared was tested by one-stage coagulation method. Then corresponding amount of protamine sulfate were added to neutralize heparin or heparin/ATⅢ to detect the FⅨ activity again. Their influence of heparin, ATⅢ and heparin/ATⅢ with different concentrations on the activity of FⅨ were analyzed. 【Results】 When the content of heparin or heparin/ATⅢ was 0, 0.1, 0.3 and 0.5 IU per unit of FⅨ, the detection results of FⅨ titer in samples were consistent. When the content of heparin or heparin/ATⅢ per unit of FⅨ was 0.8, 1, 2 and 4 IU, the detection results of FⅨ titer were all lower than those of samples without heparin. When the ATⅢ content was 0, 0.1, 0.5 and 1 IU, the FⅨ titer of the samples was consistent. 【Conclution】 When the content of heparin or heparin/ATⅢ in the product is less than or equal to 0.5 IU per IU of FⅨ, the step of protamine sulfate adding could be omitted as it has little effect on FⅨ activity. When >0.5 IU per IU of FⅨ, however, protamine sulfate adding, to neutralize heparin, is necessary before FⅨ activity testing.

The biological clock gene BMAL1 inhibits the proliferation, migration and invasion of radiation-resistant nasopharyngeal carcinoma cell line 5-8FR by regulating PI3K/Akt/MMP-2/9 signaling pathway / 中华放射肿瘤学杂志

Objective:To investigate the effect of BMAL1 gene on the proliferation, migration and invasion ability of radiation-resistant nasopharyngeal carcinoma cell line (5-8FR) and the molecular mechanism. Methods:A multi-target click model was constructed for radiation-resistant nasopharyngeal carcinoma cell line 5-8FR by low-dose fractionated irradiation, and the results of clone formation assay were used to fit the multi-target click model and calculate the sensitization ratio of radiotherapy. The expression levels of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in 5-8FR and control 5-8F cell lines were detected by Western blot. The overexpression and knockdown vectors of BMAL1 gene were constructed and transfected with 5-8F and 5-8F cell lines, respectively. The BMAL1 gene overexpression (pcDNA-BMAL1) and its control (pcDNA) and interference (BMAL1-shRNA) and control (con-shRNA) cell lines were stably transfected with nasopharyngeal carcinoma cell line 5-8F and radiation-resistant cell line 5-8FR, respectively. Western blot was performed to verify the infection efficiency and detect the changes of PI3K/Akt/MMP-2/9 signaling pathway-related proteins after overexpression or interference of BMAL1 gene in both groups of cells. CCK-8 assay, cell scratch test and Transwell chamber test were conducted to investigate the proliferation, migration and invasion capabilities of 5-8FR cell line after overexpression or interference of BMAL1 gene. Results:BMAL1 gene expression was down-regulated, and those of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9 were up-regulated, and TIMP-2 and TIMP-1 expression was down-regulated in nasopharyngeal carcinoma radiation-resistant cell lines. Overexpression of BMAL1 gene inhibited the expression of PI3K/Akt pathway proteins and downstream related molecules of MMP-2 and MMP-9, promoted the expression of TIMP-2 and TIMP-1, and inhibited the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cells, while interference with BMAL1 gene yielded the opposite results. Conclusions:BMAL1 gene can reverse the expression of PI3K/Akt/MMP-2/9 signaling pathway-related proteins in radiation-resistant nasopharyngeal carcinoma cell lines and inhibit the proliferation, migration and invasion capabilities of radiation-resistant nasopharyngeal carcinoma cell lines.

Application of ureteral access sheath in the operation of middle and lower ureteral calculi in patients with massive benign prostatic hyperplasia / 中华外科杂志

Objective: To examine the effectiveness and safety of application of the ureteral access sheath in the treatment of middle or lower ureteral calculi in patients with large-volume benign prostatic hyperplasia above grade Ⅲ, which is expected to avoid the simultaneous or staged treatment of benign prostatic hyperplasia via eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia. Methods: From April 2018 to December 2020, the clinical data of 27 patients with massive benign prostatic hyperplasia above grade Ⅲ and middle and lower ureteral calculi treated with indwelling ureteral access sheath plus ureteroscopy holmium laser lithotripsy at Department of Urology, Zhejiang Quhua Hospital were retrospectively analyzed and followed up. All the patients were male, aged (69.7±12.8) years (range: 55 to 87 years). Prostate volume measured by transrectal ultrasound was (94.8±16.2) cm3 (range: 85 to 186 cm3). The ureteral access sheath was indwelled in advance, and then the semirigid ureteroscopy was introduced through the working channel of the sheath. Holmium laser lithotripsy was performed, and intraoperative and postoperative complications were recorded. Urinary abdominal plain X-ray or CT urography were performed at 1-and 2-month postopaerative to evaluate the residual stones and clinical efficacy. Results: The ureteral access sheath was placed and holmium laser lithotripsy under a semirigid ureteroscopy was performed successfully in all the 27 patients. In 2 patients, a second session of auxiliary procedure was required due to the large load of preoperative stones and residual stones after surgery, among whom 1 patient received extracorporeal shock wave lithotripsy and 1 patient underwent extracorporeal shock wave lithotripsy plus ureteroscopic lithotripsy. The stone free rate at 1-and 2-month postoperative were 92.6% (25/27) and 100% (27/27), respectively. There were no severe complications such as ureteral avulsion and perforation, perirenal hematoma, septic shock, severe hematuria, urinary retention, iatrogenic ureteral stricture occurred during and after the surgery. The ureteral calculus was wrapped by polyps heavily in 1 patient, he was diagnosed as ureteral stenosis 1 month postoperative, receiving laparoscopic resection of ureteral stricture plus anastomosis 3 months postoperative. Conclusions: In the operations of middle and lower ureteral calculi in patients with large-volume prostatic hyperplasia above grade Ⅲ, the ureteral access sheath can be placed first to effectively eliminate the difficult angle and resistance of ureteroscopy caused by severe prostatic hyperplasia, and then semirigid ureteroscopic lithotripsy can be safely performed. It could avoid the treatment of benign prostatic hyperplasia at the same time or by stages.

Mixed responses to first-line alectinib in non-small cell lung cancer patients with rare ALK gene fusions: A case series and literature review.

Anaplastic lymphoma kinase (ALK) fusion is a well-defined biomarker for ALK tyrosine kinase inhibitors (TKIs) treatment in non-small cell lung cancer (NSCLC). Alectinib, a second-generation ALK-TKI, has been shown to have significantly longer progression-free survival (PFS) than first-generation ALK inhibitors in untreated ALK-rearranged NSCLC patients. However, its clinical efficacy on rare ALK fusions remains unclear. Herein, two advanced NSCLC patients received first-line alectinib treatment, given their positive ALK fusion status as determined by immunohistochemistry (IHC) testing results. Patients showed limited clinical response (PFS: 4 months) and primary resistance to alectinib respectively. Molecular profiling using next-generation sequencing (NGS) further revealed a striatin (STRN)-ALK fusion in the first patient accompanied by MET amplification, and a LIM domain only protein 7 (LMO7)-ALK fusion in another patient without any other known oncogenic alterations. Both patients demonstrated improved survival after they switched to second-line crizotinib (PFS: 11 months) and ensartinib (PFS: 18 months), respectively, up till the last follow-up assessment. In conclusion, the clinical efficacy of ALK-TKIs including alectinib for lung cancer with uncommon ALK gene fusions is still under evaluation. This study and literature review results showed mixed responses to alectinib in NSCLC patients who harboured rare ALK fusions. Comprehensive molecular profiling of tumour is thus strongly warranted for precise treatment strategies.

Robust Orthogonal-View 2-D/3-D Rigid Registration for Minimally Invasive Surgery.

Intra-operative target pose estimation is fundamental in minimally invasive surgery (MIS) to guiding surgical robots. This task can be fulfilled by the 2-D/3-D rigid registration, which aligns the anatomical structures between intra-operative 2-D fluoroscopy and the pre-operative 3-D computed tomography (CT) with annotated target information. Although this technique has been researched for decades, it is still challenging to achieve accuracy, robustness and efficiency simultaneously. In this paper, a novel orthogonal-view 2-D/3-D rigid registration framework is proposed which combines the dense reconstruction based on deep learning and the GPU-accelerated 3-D/3-D rigid registration. First, we employ the X2CT-GAN to reconstruct a target CT from two orthogonal fluoroscopy images. After that, the generated target CT and pre-operative CT are input into the 3-D/3-D rigid registration part, which potentially needs a few iterations to converge the global optima. For further efficiency improvement, we make the 3-D/3-D registration algorithm parallel and apply a GPU to accelerate this part. For evaluation, a novel tool is employed to preprocess the public head CT dataset CQ500 and a CT-DRR dataset is presented as the benchmark. The proposed method achieves 1.65 ± 1.41 mm in mean target registration error(mTRE), 20% in the gross failure rate(GFR) and 1.8 s in running time. Our method outperforms the state-of-the-art methods in most test cases. It is promising to apply the proposed method in localization and nano manipulation of micro surgical robot for highly precise MIS.