Mechanism studies underlying the alleviatory effects of isoliquiritigenin on abnormal glucolipid metabolism triggered by type 2 diabetes / 药学学报

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

The combination of berberine and cinnamon polyphenol can improve glucose metabolism in T2DM rats through Bas-TGR5-GLP-1 / 药学学报

Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.

Comparison of clinical efficacy and stability of Toric implantable collamer lens implantation in different orientations / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the clinical efficacy, vault, and rotational stability of horizontal, oblique, and vertical implantation of Toric implantable collamer lens(TICL).METHODS: Retrospective cohort study. A total of 92 cases(120 eyes)who underwent TICL implantation from July 2018 to March 2022 and had regular follow-up for at least 1 a postoperatively(1 d, 1 wk, 1, 3, 6 mo, and 1 a)at Wuhan Bright Eye Hospital were collected. The patients were divided into three groups, with 34 cases(45 eyes)in horizontal implantation group, 25 cases(29 eyes)in oblique implantation group(29 cases), and 33 cases(46 eyes)in vertical implantation group. Uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA), diopters, vault, and rotation angle(deviation of the actual axis of TICL from the expected axis).RESULTS: All surgeries were uneventful, and there were no complications such as infection, secondary glaucoma, or cataract opacity. Safety and efficacy of the surgery: the CDVA of the three groups of patients was better than or equal to the preoperative CDVA at 1 a postoperatively, and there was no statistically significant differences in postoperative UDVA and CDVA of the three groups(P&#x0026;#x003E;0.05). The safety index at 1a postoperatively was 1.34±0.21, 1.34±0.17, and 1.31±0.18 for the horizontal, oblique, and vertical groups, respectively. The efficacy index was 1.26±0.21, 1.33±0.18, and 1.27±0.16 for the three groups, respectively, both with no statistically significant differences(P&#x0026;#x003E;0.05). Vault: there was a significant difference in postoperative vault among the three groups(P=0.003), with the vertical group having the lowest vault, followed by the horizontal group and the oblique group. The vaults at different follow-up time points within each group showed significant differences(P&#x0026;#x003C;0.001), and all decreased over time. Residual astigmatism: there was no significant difference in residual astigmatism among the three groups(P=0.130), but there were differences at different follow-up time points within each group(P&#x0026;#x003C;0.001). Rotation angle: no significant differences in rotation angle were observed among the three groups(P=0.135), but there were differences at different follow-up time points within each group(P&#x0026;#x003C;0.001).CONCLUSION: The implantation of TICL in different orientations has good safety and efficacy, the postoperative rotational stability is good, and the appropriate angle can be selected to implant TICL according to the clinical situation.

Analysis of three-dimensional visualization imaging of severe portal vein stenosis after liver transplantation and clinical efficacy of portal vein stent implantation / 器官移植

Objective To analyze three-dimensional imaging characteristics and advantages for severe portal vein stenosis after liver transplantation, and to evaluate clinical efficacy of portal vein stent implantation. Methods Clinical data of 10 patients who received portal vein stent implantation for severe portal vein stenosis after liver transplantation were retrospectively analyzed. Imaging characteristics of severe portal vein stenosis, and advantages of three-dimensional reconstruction imaging and interventional treatment efficacy for severe portal vein stenosis were analyzed. Results Among 10 patients, 3 cases were diagnosed with centripetal stenosis, tortuosity angulation-induced stenosis in 2 cases, compression-induced stenosis in 2 cases, long-segment stenosis and/or vascular occlusion in 3 cases. Three-dimensional reconstruction images possessed advantages in accurate identification of stenosis, identification of stenosis types and measurement of stenosis length. All patients were successfully implanted with portal vein stents. After stent implantation, the diameter of the minimum diameter of portal vein was increased [(6.2±0.9) mm vs. (2.6±1.7) mm, P<0.05], the flow velocity at anastomotic site was decreased [(57±19) cm/s vs. (128±27) cm/s, P<0.05], and the flow velocity at the portal vein adjacent to the liver was increased [(41±6) cm/s vs. (18±6) cm/s, P<0.05]. One patient suffered from intrahepatic hematoma caused by interventional puncture, which was mitigated after conservative observation and treatment. The remaining patients did not experience relevant complications. Conclusions Three-dimensional visualization technique may visually display the location, characteristics and severity of stenosis, which is beneficial for clinicians to make treatment decisions and assist interventional procedures. Timely implantation of portal vein stent may effectively reverse pathological process and improve portal vein blood flow.

Methodological Evaluation of Advantages of Traditional Chinese Medicine Treatment of Sjögren's Syndrome / 中国实验方剂学杂志

Screening and evaluating the diseases responding specifically to traditional Chinese medicine （TCM） will help to highlight the advantages of TCM treatment， and the evaluation method should be standardized with consideration to the unique characteristics of the diseases. The incidence of Sjögren's Syndrome （SS） is increasing year by year， while the pathogenesis of this disease remains unclear. Modern therapies for this disease include biological agents and immunosuppressants， which generally have unsatisfactory efficacy. The TCM treatment of SS focuses on the harmony of the physical and mental health. The Rheumatology Branch of the China Association of Chinese Medicine organizes experts in TCM， Western medicine， and evidence-based medicine to form working groups. Delphi method and bibliometric method were used for analysis， and SS was selected as a disease responding specifically to TCM. Furthermore， the evaluation system was established for this disease， and the consensus regarding this disease was reached after seminar discussion. This paper summarized the whole process of the evaluation of the advantages of TCM treatment of SS. First， because TCM atomization is widely used in clinical practice and enriches TCM administration methods， this therapy is included after other non-drug therapies were taken as characteristic therapies. Second， the evaluation indicators of therapeutic effect should be determined with consideration to international acceptance and the current research status. Third， the expression method should be accurate， standardized， and objective， highlight the natural advantages of TCM， and avoid arbitrary extension. This paper provides a reference for clinicians to explore other diseases responding specifically to TCM.

Sputum bacterial culture and drug resistance of 475 patients with pneumonia / 公共卫生与预防医学

Objective To understand the distribution and drug resistance of pathogenic bacteria in sputum culture of pneumonia, and to provide evidence for the rational application of clinical antibacterial drugs . Methods The clinical data of 475 patients with positive sputum bacterial culture admitted to department of respiratory medicine of Neijiang Hospital of Traditional Chinese Medicine from May 2020 to May 2023 were collected. The types and drug resistance of pathogenic bacteria isolated from sputum culture were statistically analyzed . Results A total of 539 strains of pathogenic bacteria were isolated from the sputum culture of 475 patients with pneumonia, including 344 strains (63.82%) of Gram-negative bacteria [mainly Klebsiella pneumoniae (79 strains, 14.66%)] and 195 strains (36.18%) of Gram-positive bacteria [mainly Streptococcus pneumoniae (70 strains, 12.99%)]. Klebsiella pneumoniae was highly sensitive to aztreonam, levofloxacin, amikacin, imipenem, and ertapenem, with the sensitivity rates of 94.67%, 92.41%, 94.87%, 96.00% and 98.67% respectively. Streptococcus pneumoniae was absolutely sensitive to teicoplanin, vancomycin and linezolid, and was highly sensitive to cefpirome, levofloxacin, imipenem and ertapenem, with the sensitivity rates of 94.29%, 91.43%, 97.14% and 98.48%. Conclusions The common pathogenic bacteria of patients with pneumonia in Neijiang Hospital of Traditional Chinese Medicine include Klebsiella pneumoniae and Streptococcus pneumoniae. Various pathogenic bacteria have different degrees of resistance to common antibacterial drugs. It is necessary to combine with the types and drug susceptibility results of pathogenic bacteria for the rational application of antibacterial drugs.

Application of Animal Models of Corneal Neovascularization Based on Data Mining / 中国实验方剂学杂志

ObjectiveTo provide a reference for the establishment of an ideal corneal neovascularization （CNV） animal model by summarizing the modeling characteristics of CNV animal models. MethodWith "CVN" as the theme word， this paper searched the China National Knowledge Infrastructure （CNKI）， Wanfang， Chinese medical journals full-text database， and PubMed database and screened out relevant literature on CNV animal experiments from 2013 to 2023. The database was established by Excel 2021， and the experimental animal strain， gender， modeling method， detection index， and application category were sorted out. The characteristics of the CNV animal model were analyzed. ResultAfter comparative analysis， it was found that the animal strains were Sprague-Dawley rats （87 times， 29.49%） and New Zealand white rabbits （52 times， 17.63%）. Male animals were recommended. Most modeling methods for efficacy verification and mechanism studies were the alkali burn method. Index detection methods included apparent index observation， histopathological detection， immunohistochemistry （IHC）， Western blot， and various polymerase chain reaction （PCR） tests. Detection indexes included apparent indication， corneal histopathology， CNV regulation， etc. ConclusionThe CNV model of SD rats induced by the alkali burn method is recommended for model replication， and the indexes are mainly selected from the growth of CNV， corneal histopathological test， and vascular endothelial growth factor （VEGF）-related test. In addition， according to the demand， the corneal apparent indication and the basic indexes related to the regulation of CNV， such as vascular endothelial growth factor receptor 2 （VEGFR2）， basic fibroblast growth factor （bFGF）， and secretogranin Ⅲ （Scg3） are also selected. Clinical treatment of CNV relies on anti-inflammatory drugs and anti-VEGF drugs， and there is a lack of application of traditional Chinese medicine （TCM）， so the model needs to be improved by adding elements of TCM syndromes.

Age Discrimination Based on Volatile Components of Arisaema Cum Bile / 中国实验方剂学杂志

ObjectiveTo discriminate the age of Arisaema Cum Bile， the combination of headspace solid-phase microextraction （HS-SPME） with gas chromatography-mass spectrometry （GC-MS） was applied to explore the differences of volatile components of unfermented， 1-year fermented， 2-year fermented， and 3-year fermented Arisaema Cum Bile. MethodSamples with different fermentation durations were collected and HS-SPME-GC-MS technology was employed to detect the volatile components of each sample. The relative contents of detected volatile components were processed and analyzed by chemometrics methods such as principal component analysis （PCA）， hierarchical cluster analysis （HCA）， and partial least squares discriminant analysis （PLS-DA）. ResultThe results showed that 145 volatile components were identified. Among these volatile components， the relative contents of heterocyclic， alcohols， aldehydes and aromatics were high. PCA， HCA， and PLS-DA can effectively separate Arisaema Cum Bile with four different ages. Based on variable importance in projection （VIP） value > 1， 73 markers of differential volatile components were identified. The content of 2，6，11-trimethyldodecane and m-xylene in unfermented samples was the highest， and the content difference between them and those in fermented samples was significant （P<0.05）. 2，3-butanediol was detected only in 1-year samples， octane was detected only in 2-year samples， and ethyl heptanoate was detected only in 3-year samples. These components can be used as odor markers for Arisaema Cum Bile with different fermentation years. ConclusionThe identification method of volatile components of Arisaema Cum Bile was established by HS-SPME-GC-MS technology， which can realize the rapid identification of unfermented， 1-year fermented， 2-year fermented， and 3-year fermented samples， and provide a scientific basis for the standardization of processing technology and quality standards of Arisaema Cum Bile.

One case of myocardial damage caused by carbamate pesticide poisoning / 中华劳动卫生职业病杂志

The data of a patient with carbamate pesticide poisoning were analyzed. Cardiac arrest, oliguria, acute renal injury and pulmonary infection occurred during treatment. After cardiopulmonary resuscitation, tracheal intubation, CRRT, anti-infection and other symptomatic support treatment, the patient recovered and discharged. The myocardial damage caused by carbamate pesticide poisoning is easy to be ignored, and it often causes cardiac manifestations such as arrhythmia and cardiac insufficiency, and the related markers of cardiac injury, electrocardiogram and echocardiogram are also changed. Therefore, the awareness of cardiac damage caused by carbamate pesticide poisoning should be improved.

Pathological classification of malignant peritoneal mesothelioma and comparative analysis with peritoneal carcinomatosis / 中华劳动卫生职业病杂志

Objective: To analyze the pathological classification of malignant peritoneal mesothelioma (MPeM) and screen the immunohistochemical markers that can distinguish MPeM from peritoneal metastatic carcinoma (PC) . Methods: In June 2020, the pathological results of peritoneal biopsy of 158 MPeM and 138 PC patients from Cangzhou Central Hospital, Cangzhou People's Hospital, and Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine from May 2011 to July 2019 were retrospectively analyzed, and the pathological classifications of MPeM in Cangzhou were summarized. Immunohistochemical markers of MPeM and PC patients were analyzed, and receiver operating characteristic curve (ROC curve) was drawn for differential diagnosis of MPeM and PC. Results: There were 55 male and 103 female MPeM patients in Cangzhou, with an average age of 57.1 years old. The asbestos exposure rate was 91.14% (144/158). The most common pathological classifications were cutaneous type, accounting for 90.51% (143/158). There were significant differences in the expression of calreticulum protein, CK5/6, vimentin, D2-40, carcinoembryonic antigen (CEA) and tail type homologous nuclear gene transcription factor 2 (CDX-2) between MPeM and PC (P<0.05). Among the 6 positive markers, the sensitivity of calreticulum protein was the highest (0.905) and CEA was the lowest (0.428) . Conclusion: Calreticulum protein, CK5/6, vimentin, D2-40, CEA and CDX-2 may be used as specific markers to distinguish the diagnosis of MPeM from PC.

Analysis of work stress and its influencing factors among nursing staff in Tianjin City / 中华劳动卫生职业病杂志

Objective: To explore the current situation of work stress among nursing staff in Tianjin City and analyze its influencing factors. Methods: From August to October 2020, 26002 nursing staff from tertiary hospitals, secondary public hospitals, secondary private hospitals, primary hospitals, and other medical institutions in Tianjin City were selected as objects, and their general situation and working stress situation were surveyed by the general information questionnaire and the Nurse's Work Stressor Scale. Single factor analysis and multiple linear regression analysis were used to explore the influencing factors of work stress among nursing staff. Results: The average age of 26002 nursing staff was (33.86±8.28) years old, and the average working years were (11.84±9.12) years. There were 24874 women (95.66%) and 1128 men (4.34%). The total score of work stress was (79.82±21.69), and the average score of workload and time allocation dimension was the highest (2.55±0.79). The results of multiple linear regression analysis showed that marital status (β=-0.015, P=0.014), employment form as contract system (β=0.022, P=0.001), post as clinical nursing (β=0.048, P<0.001), education level (β=0.024, P<0.001), age (β=0.050, P<0.001), working years (β=0.075, P<0.001), and professional title (β=0.036, P<0.001) were the influencing factors of work stress, which explained 22.8% of the total variation in work stress of nursing staff (F=24.25, P<0.001) . Conclusion: The work stress among nursing staff in Tianjin City is high, the corresponding departments and nursing managers should adopt scientific management methods to reduce the workload of nursing staff according to the influencing factors of work stress, so as to create a good atmosphere for further promoting the healthy development of nursing career and nursing industry in the new era.

Dihydroartemisinin Regulates Neuro-microglia to Relieve Neuropathic Pain / 中国实验方剂学杂志

ObjectiveTo evaluate the intervention effect of dihydroartemisinin （DHA） on hippocampal nerve injury in L5 spinal nerve ligation （SNL） model and tumor necrosis factor-α （TNF-α） hippocampal continuous injection model. In primary cultured microglia-hippocampal neurons， the regulatory pattern of DHA on microglia-hippocampal neuronal interactions was confirmed. MethodThe experimental animals were divided into Sham group， SNL group， and DHA group （16 mg·kg-1）， with 3 mice in each group. The hippocampal CA3 glutamatergic neurons were labeled with adeno-associated virus ［Calmodulin-dependent protein kinase Ⅱ（CaMKⅡ） dTomato AAV］， and their contributions to the hippocampal CA1， prefrontal cortex （Frc）， anterior cortex （ACC）， projections of nucleus accumbens （Nac）， and Basolateral Amygdala （BLA） were traced by immunofluorescence staining. The experimental animals were divided into a Sham group， a TNF-α hippocampus continuous injection model group， DHA-L， DHA-M， and DHA-H groups （4， 8， 16 mg·kg-1）， and pregabalin group （25 mg·kg-1）， with 4 mice in each group. The morphology of pyramidal neurons in the hippocampal CA1 and CA3 regions was counted by Golgi staining. The continuous activation of hippocampal primary neurons and microglia was induced， DHA intervention was given by co-culture， and the cell soma area and the expression of postsynaptic density protein 95 （PSD95） inside and outside the primary and secondary dendritic spines of neurons were counted by immunofluorescence. ResultCompared with the Sham group， the projection of CA3 glutamatergic neurons to CA1 region， Frc， and ACC in the SNL group was significantly reduced （P<0.01）， while the projection to Nac and BLA was significantly increased （P<0.01）. As compared with the SNL group， the projection of hippocampal CA3 glutamatergic neurons to CA1 region， Frc， and ACC was significantly increased in the DHA group （P<0.01）， while the projection to Nac and BLA was significantly reduced （P<0.01）. Golgi staining results showed that as compared with the Sham group， the density of dendritic spines and the number of dendritic branches in the CA1 and CA3 pyramidal neurons in the TNF-α hippocampal continuous injection model group were significantly reduced （P<0.01）. As compared with the TNF-α hippocampal continuous injection model， the density of dendritic spines and the number of dendritic branches in hippocampal CA1 and CA3 pyramidal neurons in the DHA-M and DHA-H groups were significantly increased （P<0.05， P<0.01）. Compared with DHA-M group， the total dendrite length of CA1 pyramidal neurons in hippocampus in DHA-H group was significantly increased （P<0.01）， while the total dendrite length of CA1 neurons and the total dendrite base length of CA3 neurons in DHA-L group was significantly decreased （P<0.01）. Compared with the blank control group， the cell soma area of the glycine group and glutamate group increased significantly （P<0.01）. As compared with the glycine group and glutamate group， the cell area of the glycine + glutamate group was significantly increased （P<0.01）， and as compared with the glutamate group， the cell soma area of the glutamate + DHA group was significantly reduced （P<0.01）. As compared with the glycine acid + glutamate group， the cell soma area of the glycine + glutamate + DHA group was significantly reduced （P<0.01）， and as compared with the glutamate + DHA group， the cell soma area of the glycine + glutamate + DHA group was also significantly reduced （P<0.05）. Compared with the blank control group， the cell soma area of the glutamate group was significantly increased （P<0.01）. As compared with the glutamate group， the cell soma area of the glutamate + DHA-L， glutamate + DHA-M， and glutamate + DHA-H groups was significantly reduced （P<0.01）. As compared with the blank control group， the expression of the resting primary microglia + glycine group in primary and secondary dendritic internal and external postsynaptic density protein 95 （PSD95） was significantly increased （P<0.01）. As compared with the resting primary microglia + glycine group， the expression of PSD95 in the primary and secondary dendritic spinous and external neurons of the activated primary microglia + glycine group was significantly reduced （P<0.01）. As compared with the activated primary microglia + glycine group， the expression of PSD95 in the primary and secondary dendritic spinous and external neurons in the activated primary microglia + glycine + DHA group was significantly increased （P<0.01）. As compared with the activated primary microglia + DHA group， the expression of PSD95 in the primary and secondary dendritic spines and outside neurons in the activated primary microglia + glycine + DHA group was significantly increased （P<0.01）. ConclusionDHA has a significant repair effect on vertebral neuronal damage caused by hippocampal microglia and TNF-α overexpression in NP pathology， and this repair is closely related to the dual inhibition of neuronal-microglia by DHA.

Recent Progress of Tertiary Lymphoid Structure in Prognosis and Immunotherapy of Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is the leading cause of cancer death, and non-small cell lung cancer (NSCLC) accounts for 85%. Immunotherapy has significantly improved the clinical prognosis of patients with NSCLC. However, because of the complexity and heterogeneousness of the tumor microenvironment, only a subset of individuals can benefit from immunotherapy. Therefore, it is necessary to explore effective predictive biomarkers for immunotherapy of NSCLC. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ that is highly similar to secondary lymphoid organs (SLO), and the presence of TLS has been found to be closely associated with a good prognosis in immunotherapy for a variety of solid tumors, including NSCLC. This article provides a review of the prognostic role of tertiary lymphoid structures in immunotherapy of NSCLC, in order to offer references for screening suitable candidates for immunotherapy of NSCLC and develop personalized and precise treatment plans.
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Novel CD19-KIRS2/Dap12-BB CAR-T Treatment for 3 Patients with Relapsed and Refractory B-Cell Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM).@*METHODS@#Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed.@*RESULTS@#After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively.@*CONCLUSION@#The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.

Automatic sleep staging model based on single channel electroencephalogram signal / 生物医学工程学杂志

Sleep staging is the basis for solving sleep problems. There's an upper limit for the classification accuracy of sleep staging models based on single-channel electroencephalogram (EEG) data and features. To address this problem, this paper proposed an automatic sleep staging model that mixes deep convolutional neural network (DCNN) and bi-directional long short-term memory network (BiLSTM). The model used DCNN to automatically learn the time-frequency domain features of EEG signals, and used BiLSTM to extract the temporal features between the data, fully exploiting the feature information contained in the data to improve the accuracy of automatic sleep staging. At the same time, noise reduction techniques and adaptive synthetic sampling were used to reduce the impact of signal noise and unbalanced data sets on model performance. In this paper, experiments were conducted using the Sleep-European Data Format Database Expanded and the Shanghai Mental Health Center Sleep Database, and achieved an overall accuracy rate of 86.9% and 88.9% respectively. When compared with the basic network model, all the experimental results outperformed the basic network, further demonstrating the validity of this paper's model, which can provide a reference for the construction of a home sleep monitoring system based on single-channel EEG signals.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Immunophenotype and function of peripheral blood lymphocyte subsets in Chinese rhesus macaques / 中华微生物学和免疫学杂志

Objective:To provide data reference for using Chinese rhesus macaques as research model by studying the immunophenotype and function of peripheral blood lymphocytes in Chinese rhesus macaques.Methods:By optimizing antibody clones and fluorescent colors, the lymphocyte subset assay and T cell function assay panels were determined. Then the panels were used to analyze the proportion of T, B, NK and other cell subsets in peripheral blood mononuclear cells (PBMCs) in 15 healthy Chinese rhesus monkeys, and the ability of T cells to secrete cytokines after non-specific stimulation.Results:Two multi-color flow cytometry analytic panels were established. Panel 1 could simultaneously detect a variety of lymphocyte subsets, including cytotoxic T lymphocytes, follicular helper T cells, regulatory T cells, B cells and NK cells. Panel 2 could detect the functions of multiple T cell subsets and the expression of immune checkpoint moleculars. The mean percentages of T, B, NK, Tfh, Treg, CD16 + NK and CD56 + NK cells in PBMCs of the Chinese rhesus macaques were (75.32±7.73)%, (13.22±7.50)%, (0.88±0.48)%, (0.73±0.27)%, (0.75±0.43)%, (47.87±22.35)% and (10.69±12.41)%. After non-specific stimulation, the proportion of CD4 + T cells secreting IL-2 and TNF-α was higher than that of CD8 + T cells, and the proportion of CD8 + T cells secreting CD107a and IFN-γ was higher than that of CD4 + T cells, while the proportion of CD4 + and CD8 + T cells secreting IL-17A was low. Conclusions:This study established a multi-color flow detection scheme that could simultaneously detect multiple cellular surface molecules and cytokines at the single cell level and could accurately and comprehensively analyze the immune cell subsets, functions and the immune checkpoint molecules in peripheral blood of Chinese rhesus macaques, providing a new experimental method and basic data for the development of vaccines and drugs against infectious diseases.

Effectiveness of pelvic floor muscle biofeedback electrical stimulation combined with pelvic floor muscle training for mild to moderate postpartum stress urinary incontinence / 中华围产医学杂志

Objective:To analyze the effects of pelvic floor muscle biofeedback electrical stimulation (PEMS) combined with pelvic floor muscle training (PFMT) and PFMT alone on mild to moderate stress urinary incontinence (SUI) after delivery.Methods:This retrospective study involved 1 087 postpartum women with mild or moderate SUI who were admitted to the Affiliated Hospital of Jining Medical University from January 2017 to January 2021. According to the treatment approaches, they were divided into two groups: the PMES+PFMT group ( n=504) and the PFMT group ( n=583). Chi-square test, independent sample t-test and rank sum test were used to compare the objective indicators (pelvic floor muscle strength test, vaginal dynamic pressure value test, 1-h pad test) and subjective indicators [incontinence impact questionnaire short form (IIQ-7), incontinence questionnaire-urinary incontinence short form (ICI-Q-SF), pelvic organ prolapse/urinary incontinence sexual function questionnaire (PISQ-12)] before, immediate and three months after treatment between the two groups. Results:There was no significant difference between the two groups in the values of vaginal dynamic pressure before treatment, 1-h pad test results and subjective indicators (all P>0.05). Comparison within groups: Indicators were improved in both groups immediate and three months after treatment compared with before treatment, including strength of type Ⅰ muscle [PMES+PFMT group: grade 4 and 5 (normal): 43.5% (219/504) and 42.1% (212/504) vs 1.2% (6/504), χ 2=864.27 and 861.46; PFMT group: grade 4 and 5:19.2% (112/583) and 20.1% (117/583) vs 1.5% (9/583), χ 2=1 148.26 and 1 038.29] and class Ⅱ muscle strength [PMES+PFMT group: 48.4% (244/504) and 50.8% (256/504) vs 4.8% (24/504), χ 2=862.96 and 819.24; PFMT group: 37.4% (218/583) and 38.9% (227/583) vs 5.0% (29/583), χ 2=1 029.47 and 998.54; all P < 0.05].Vaginal dynamic pressure increased [PMES+PFMT group: (89.3±5.4) and (82.2±4.6) vs (67.5±12.7) cmH 2O (1 cmH 2O=0.098 kPa), t=802.13 and 845.54; PFMT group:(80.2±4.3) and (78.6±4.5) vs (66.9±14.2) cmH 2O, t=288.37 and 244.94], and 1-hour urine leakage reduced [PMES+PFMT group: 2.0 g (2.0-3.0 g) and 2.0 g (1.0-3.0 g) vs 6.0 g (5.0-6.0 g), Z=825.39 and 802.13; PFMT group: 4.0 g (3.0-5.0 g) and 3.0 g (3.0-4.0 g) vs 5.0 g (4.0-6.0 g), Z=836.34 and 811.25], and IIQ-7 scores [PMES+PFMT group: scores of 3 (2-4) and 4 (3-4) vs 8 (7-9), Z=959.52 and 825.87; PFMT group: 5 (4-5) and 5 (4-6) vs 8 (7-10), Z=916.27 and 903.18], and ICI-Q-SF score [PMES+PFMT group: 3.5 (3-4) and 4 (3-5) vs 10 (9-12), Z=952.79 and 924.94; PFMT group: 6 (4-7) and 6 (5-7) vs 11 (10-12), Z=1 049.89 and 998.15], and PISQ-12 score [PMES+PFMT group: 10 (7-12) and 9 (7-12) vs 21 (17-24), Z=862.55 and 887.17; PFMT group: 13 (11-16) and 14 (12-16) vs 22 (18-25), Z=1 026.73 and 934.86, all P<0.05) decreased. Compared with the PFMT group, the above indexes were all better in the PMES+PFMT group (all P<0.05). Conclusion:PFMT alone or in combination with PMES can both enhance pelvic floor muscle strength, increase vaginal dynamic pressure, alleviate urine leakage and improve the quality of life and PMES+PFMT is better and more effective.

Survey on the views of general practitioners on developing special interests in the context of county medical community / 中华全科医师杂志

Objective:To explore the views of general practitioners (GPs) on developing special interests in the context of the county medical community.Methods:A survey was conducted using self-designed questionnaire from November and December 2019, among 49 general practice residents trained in the First Affiliated Hospital of Zhejiang University School of Medicine. Meanwhile, structured interviews were undertaken with 14 general practice residents.Results:Forty-nine valid questionnaires were collected with a response rate of 100.0%. All participants were from the county medical community units. The survey showed that 91.8% (45/49) of respondents were willing to develop special interests and 79.6% (39/45) chose one subject, and the top three subjects were endocrinology, gastroenterology and cardiology. The structured interviews demonstrated that most participants did not understand meaning of general practitioners with special interests (GPwSIs) clearly and were unable to distinguish GPwSIs from specialists; they were confused about the status, training mode, and assessment standards of GPwSIs. The interviews also showed that the demand for developing special interests for them was derived from the needs of patients for diagnosis and treatment, the target population of health care services, peer advice and personal interests.Conclusions:Most general practice residents are willing to develop special interests, and internal medicine is the first choice; however, their understanding of the GPwSIs is insufficient. The survey suggests that the position, training model, assessment and certification of GPwSI need to be further clarified.

The clinical characteristics and prognostic value of PSA dynamic features in patients with metastatic castration resistant prostate cancer received abiraterone acetate / 中华泌尿外科杂志

Objective:To analyze the clinical characteristics and prognostic value of prostate-specific antigen (PSA) dynamic features in patients with metastatic castration resistant prostate cancer (mCRPC) received abiraterone acetate (AA) therapy.Methods:The data of 89 patients with mCRPC who received AA therapy from January 2017 to June 2021 in Shanghai Tongji Hospital were retrospectively reviewed. The age of patients was (75.7 ± 8.3) years old, median PSA before AA was 56.88 (19.31, 143.75) ng/ml. The PSA dynamic features included PSA nadir (PSAN) and PSAN time. PSAN was defined as the lowest value of PSA after treatment, and PSAN time was defined as time to PSAN after AA treatment. PSAN was divided into 3 groups: PSAN1 (<0.1 ng/ml), PSAN2 (0.1- 4.0 ng/ml) and PSAN3 (>4.0 ng/ml) groups. PSA response was defined as a maximum PSA decline rate ≥50%, and no PSA decline after treatment was defined as primary resistance. Cox regressions adjusted to clinical factors were performed to evaluate the influence of PSA dynamic features on patients' radiographic progression-free survival (rPFS) and overall survival (OS). Log-rank test was used to evaluate the survival time of patients in different PSAN groups. Receiver operator characteristic (ROC) curve and area under the curve (AUC) were performed to analyze the predictive value of PSA dynamic features on survival outcomes of patients.Results:The follow-up time was 17 (12, 23) months, and 75 (84.3%) patients showed PSA responses. The median PSAN was 1.82 (0.01, 11.70) ng/ml, median PSAN time was 5.0(3.0, 9.5)months. Multivariate Cox regression indicated that PSAN was an independent risk factor for rPFS ( PSAN2: HR=5.308, P=0.017; PSAN3: HR=13.209, P<0.001), and PSAN time ≥ 5 months( HR=0.309, P<0.001)was an independent protective factor for rPFS. Also, the PSAN3 was an independent risk factor for OS( HR=9.459, P=0.048). Log-rank test indicated that the rPFS of PSAN1 group (median not reached) was significantly longer than PSAN2 [median 13.0(95% CI 8.2-17.8) months, P=0.001] and PSAN3 [8.0 (95% CI 4.1-11.9) months, P<0.001] groups. ROC curve and AUC showed that PSAN had a higher predictive value in rPFS outcomes compared with T stage, metastatic disease volume, and Eastern Cooperative Oncology Group (ECOG) score (0.82 vs. 0.69, 0.68, 0.53, P<0.05). PSAN had a higher predictive value in OS outcomes than metastatic disease volume and ECOG(0.83 vs. 0.63, 0.58, P<0.05). Conclusions:Lower PSAN needs longer PSAN time. PSAN is an independent risk factor for rPFS and OS, and PSAN time is an independent protective factor for rPFS.