The Application of Bacterial Outer Membrane Vesicles in Tumor Treatment / 生物化学与生物物理进展

Outer membrane vesicles (OMVs) are nanoscale vesicles secreted by Gram-negative bacteria. As a unique bacterial secretion, OMV secretion can help bacteria maintain the outer membrane stability or remove harmful substances. Studies have shown that local separation of outer membrane and peptidoglycan layers led by abnormalities in outer membrane protein function, abnormal structure or excessive accumulation of LPS, and erroneous accumulation of phospholipids in the outer leaflet, which can all lead to bacterial outer membrane protrusion and eventually bud formation of OMVs. Since OMVs are mainly composed of bacterial outer membrane and periplasmic components, the pathogen associated molecular patterns (PAMPs) on their surface can trigger strong immune responses. For example, OMVs can recruit and activate neutrophils, polarize macrophages to secrete large amounts of inflammatory factors. More importantly, OMVs can act as adjuvants to induce dendritic cell (DC) maturation to enhance adaptive immune response in the body. At the same time, OMVs are derived from bacteria, which make it easy to modify. The methods by genetic engineering and others can improve their tumor targeting, give them new functions, or reduce their immunotoxicity, which is conducive to their application in tumor therapy. OMVs not only induce apoptosis or pyroptosis of tumor cells, but also regulate the host immune system, which makes OMVs themselves have a certain killing effect on tumors. In addition, the tendency of neutrophils to inflammatory tumor sites and the formation of neutrophil extracellular traps enable OMVs to target tumor sites, and the suitable size and the characteristic that they are easily taken up by DCs give OMVs a certain lymphatic targeting ability. Therefore, OMVs are often employed as excellent drug or vaccine carriers in tumor therapy. This review mainly discusses the biological mechanism of OMVs, the regulatory effects of OMVs on immune cells, the functional modification strategies of OMVs, and their research progress in tumor therapy.

Application of MXenes in Tumor Therapy / 生物化学与生物物理进展

MXenes is an emerging two-dimensional (2D) material, which was composed of layered transition metal carbides and/or nitrides, have attracted enormous attention in the past decade since their innovative discovery by Gogotsi and Barsoum in 2011. The general formula of MXenes is Mn+1XnTx (n=1-4), where M represents transition metal elements (such as Ti, Nb, Ta, etc.), X represents carbon and/or nitrogen, and Tx represents surface terminations (such as —OH, —F, =O, etc.). In recent years, MXenes have been widely applied in the biological field due to their high biocompatibility, abundant surface groups, good conductivity and photothermal properties. Due to the strong absorption of laser in the near infrared region, strong X-ray attenuation ability and surface easily modified by various molecules or nanoparticles, MXenes have been used as photothermal agents and contrast agents in the tumor therapy and tumor diagnosis. This paper reviews the application of MXenes and MXenes-based composites in tumor therapy and active targeting tumor therapy. According to the modal of action on tumor cells, it was divided into monotherapy, bimodal therapy and trimodal therapy. Among them, the monotherapy mainly used the photothermal properties of MXenes for photothermal therapy, studies have found that MXenes QDs can be used for chemodynamic therapy. In addition, sonodynamic therapy can also be achieved by loading the sonosensitizers on the surface of MXenes. Bimodal therapy and trimodal therapy are mainly used to load anticancer drugs, photosensitizers, metal particles and other substances on the surface of MXenes to achieve combination therapy. In contrast to the limited treatment efficacy and possible side effects arising from monotherapy, the development of bimodal therapy and trimodal therapy may harbor the collective merits of respective individual treatments and give rise to much higher anticancer efficacy at lower dosage of therapeutic agents administered, thus avoiding high-dose-induced side effects. The combined use of multiple treatments displayed superior advantages over monotherapy in producing an improved therapy outcome. According to the modal of entry into tumor cells, it was divided into passive targeting and active targeting. Active targeting therapy was mainly divided into homologous targeting therapy and targeting agents targeting therapy. The strategy of homologous targeting therapy was to coat MXenes with tumor cell membrane and increased the uptake of MXenes by tumor cells. Targeting agents targeting therapy used targeting agents to specifically bind to the receptors on the surface of tumor cells, subsequently, the precise uptake of MXenes by tumor cells was achieved. Finally, the current challenges and future development trends of MXenes in preparation technology and tumor therapy are discussed.

Research progress on brain functional near-infrared spectroscopy technology in the field of neonates / 中国当代儿科杂志

Functional near infrared spectroscopy (fNIRS) is an emerging neuroimaging tool that reflects the activity and function of brain neurons by monitoring changes in brain oxygen metabolism based on the neurovascular coupling mechanism. It is non-invasive and convenient, especially suitable for monitoring neonatal brain function. This article provides a comprehensive review of research related to the developmental patterns of brain networks concerning language, music, and emotions in neonates using fNIRS. It also covers brain network imaging in neonatal care, resting-state brain network connectivity patterns, and characteristics of brain functional imaging in disease states of neonates using fNIRS.

New advances in stroke and cerebral embolism protection devices in transcatheter aortic valve replacement / 中国介入心脏病学杂志

Stroke is one of the most serious complications of transcatheter aortic valve replacement(TAVR),tremendously increasing mortality and the loss of neurocognitive function.Since TAVR is expected to further spread into lower-risk patient groups,there will be greater emphasis to obviate such serious complications.One possible technique for preventing stroke is using cerebral embolic protection devices(CEPDs).CEPDs are designed for capturing or deflecting emboli that are enter route to the brain and hence to protect the brain from embolism.Since this is a rapidly growing field with recent advances,and the impact of CEPD on preventing neurological events is still limited,there is an urgent need for understanding the role of CEPD in preventing clinically significant strokes.Although their clinical utilization is increasing,the risk factors for stroke related to TAVR and evidence for using CEPDs are not yet clear.In this review,we present an overview of the available literature on TAVR related stroke and CEPD,and outline recent advances within this field.

Screening and identification of CD44v9 specific peptide ligand for gastric cancer detection / 西安交通大学学报(医学版)

【Objective】 To screen and verify a peptide ligand specific for CD44v9. 【Methods】 A 12-mer phage peptide library was screened on CD44v9 coated on solid phase. Candidate sequences emerged after sequencing. Candidate phages were selected using enzyme-linked immunosorbent assay. The best sequence was chosen for further study. Binding of C9-3 to CD44v overexpressed HEK-293 cells was determined using immunofluorescence. Binding affinity and specificity were verified on gastric cancer tissues with immunohistochemistry. 【Results】 Phages significantly were enriched during panning process. After sequencing, nine individual sequences occurred in 30 selected clones. Among the 9 candidate sequences, C9-3 exhibited the highest frequency. Results of ELISA showed that C9-3 had the highest OD value and selectivity. Thus, C9-3 was chosen for peptide probe synthesis. C9-3 probe stained CD44v overexpressed HEK-293 cells, but not empty vector transfected HEK-293 cells. Immunohistochemistry scores of C9-3 were significantly different between gastric cancer and paracancer tissues (t=3.953, P<0.01). A linear positive correlation was observed between C9-3 binding and CD44v9 expression (r=0.823, P<0.01). 【Conclusion】 In this study, peptide ligand of CD44v9 was successfully screened. The peptide can bind to cells and cancer tissues via CD44v9. It has potential for gastric targeting probes.

Clinicopathological characteristics and prognosis of patients with small bowel tumors: A single center analysis of 220 cases / 中华胃肠外科杂志

Objective: To analyze the clinicopathological characteristics and prognosis of patients with small bowel tumors. Methods: This was a retrospective, observational study. We collected clinicopathological data of patients with primary jejunal or ileal tumors who had undergone small bowel resection in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University between January 2012 and September 2017. The inclusion criteria included: (1) older than 18 years; (2) had undergone small bowel resection; (3) primary location at jejunum or ileum; (4) postoperative pathological examination confirmed malignancy or malignant potential; and (5) complete clinicopathological and follow-up data. Patients with a history of previous or other concomitant malignancies and those who had undergone exploratory laparotomy with biopsy but no resection were excluded. The clinicopathological characteristics and prognoses of included patients were analyzed. Results: The study cohort comprised 220 patients with small bowel tumors, 136 of which were classified as gastrointestinal stromal tumors (GISTs), 47 as adenocarcinomas, and 35 as lymphomas. The median follow-up for all patient was 81.0 months (75.9-86.1). GISTs frequently manifested as gastrointestinal bleeding (61.0%, 83/136) and abdominal pain (38.2%, 52/136). In the patients with GISTs, the rates of lymph node and distant metastasis were 0.7% (1/136) and 11.8% (16/136), respectively. The median follow-up time was 81.0 (75.9-86.1) months. The 3-year overall survival (OS) rate was 96.3%. Multivariate Cox regression-analysis results showed that distant metastasis was the only factor associated with OS of patients with GISTs (HR=23.639, 95% CI: 4.564-122.430, P<0.001). The main clinical manifestations of small bowel adenocarcinoma were abdominal pain (85.1%, 40/47), constipation/diarrhea (61.7%, 29/47), and weight loss (61.7%, 29/47). Rates of lymph node and distant metastasis in patients with small bowel adenocarcinoma were 53.2% (25/47) and 23.4% (11/47), respectively. The 3-year OS rate of patients with small bowel adenocarcinoma was 44.7%. Multivariate Cox regression-analysis results showed that distant metastasis (HR=4.018, 95%CI: 2.108-10.331, P<0.001) and adjuvant chemotherapy (HR=0.291, 95% CI: 0.140-0.609, P=0.001) were independently associated with OS of patients with small bowel adenocarcinoma. Small bowel lymphoma frequently manifested as abdominal pain (68.6%, 24/35) and constipation/diarrhea (31.4%, 11/35); 77.1% (27/35) of small bowel lymphomas were of B-cell origin. The 3-year OS rate of patients with small bowel lymphomas was 60.0%. T/NK cell lymphomas (HR= 6.598, 95% CI: 2.172-20.041, P<0.001) and adjuvant chemotherapy (HR=0.119, 95% CI: 0.015-0.925, P=0.042) were independently associated with OS of patients with small bowel lymphoma. Small bowel GISTs have a better prognosis than small intestinal adenocarcinomas (P<0.001) or lymphomas (P<0.001), and small bowel lymphomas have a better prognosis than small bowel adenocarcinomas (P=0.035). Conclusions: The clinical manifestations of small intestinal tumor are non-specific. Small bowel GISTs are relatively indolent and have a good prognosis, whereas adenocarcinomas and lymphomas (especially T/NK-cell lymphomas) are highly malignant and have a poor prognosis. Adjuvant chemotherapy would likely improve the prognosis of patients with small bowel adenocarcinomas or lymphomas.

Expression of high-mobility group B1 released by exosome in nonalcoholic fatty liver disorder and regulated by TLR4 signal / 解放军医学杂志

Objective To investigate the release of enterogenic and hepatogenic high mobility group protein B1(HMGB1)through exosomes and its regulatory pathway.Methods We used wild-type(WT)and ASC-/-mice for this study.We randomly selected five mice per group from each strain and fed them either a normal diet(ND)or a high-fat diet(HFD)for eight weeks.The control group consisted of WT mice fed with the normal diet;the HFD group were WT mice with the HFD;the microflora disturbance(MD)group were ASC-/-mice fed with the normal diet;the high-lipid microflora disturbance(HLMD)group were ASC-/-mice with HFD.We used confocal microscopy to detect the co-localization of liver and intestinal exosome markers with HMGB1.We then measured the expression level of HMGB1 content in exosomes by Western blotting and PCR.The AML12 cells were treated with palmitic acid(PA)and lipopolysaccharide(LPS)for 24 h to build an in vitro model.We also detected HMGB1/CD63 levels using Western blotting.To understand the regulatory mechanism of exosome release,we employed siRNA intervention.Results The secretion of exosomes increased significantly in HFD group compared with control group[(3.5±0.2)ng/ml vs.(1.1±0.3)ng/ml,P<0.05],HLMD group compared with those in MD group[(3.2±0.2)ng/ml vs.(1.9±0.4)ng/ml,P<0.05].Using immunofluorescence detection,we observed increased co-localization of exosome markers(ALP or VPS16)with HMGB1 in HFD group compared with control group.We also observed this in AML12 cells treated with PA and LPS compared with blank control.The PCR data showed that HMGB1 in hepatocyte exosomes was higher in HFD group compared with control group(41.5±10.2 vs.1.3±0.3,P<0.05),HLMD group was significantly higher than that in MD group(48.6±7.2 vs.1.5±0.5,P<0.05).TLR4 expression was higher in HFD group compared with control group(13.8±6.2 vs.2.8±0.9,P<0.05),HLMD group compared with MD group(22.6±4.1 vs.2.5±1.5,P<0.05).In intestinal mucosal cells,the co-location of HMGB1 and exosome marker CD63 was significantly higher in HFD group compared with control group(0.6±0.2 vs.0.4±0.1,P<0.05),and HLMD group compared with MD group(0.9±0.2 vs.0.5±0.1,P<0.05).In vitro,the HMGB1 of exosomes was increased in endotoxin group(5.1±0.8)and high lipid endotoxin group(5.5±0.7)compared with control group(3.8±0.6,P<0.05).On the other hand,the HMGB1 of exosomes in the cell siRNA intervention group was not increased compared with control group(3.7±0.6 vs.3.8±0.6,P>0.05).Conclusion HMGB1 is released by exosomes in hepatocytes and intestinal cells,and regulated by Toll-like receptor 4(TLR4)under a high-fat diet and intestinal flora disorder,which may be one of the contributing factors in promoting the development of steatohepatitis.

Evaluation system of ideological and political education in clinical medicine courses based on analytic hierarchy process and fuzzy comprehensive evaluation models / 中华医学教育探索杂志

Objective:To explore the construction and application of the evaluation system for ideological and political education in clinical medicine courses based on analytic hierarchy process (AHP) and fuzzy comprehensive evaluation (FCE) models.Methods:The evaluation system for ideological and political education in clinical medicine courses was constructed based on AHP and FCE models in the Yaahp software. Ideological and political education checklist teaching that places equal emphasis on medical ethics and skill was implemented in internal medicine course taken by 185 students in The First Affiliated Hospital of Xi'an Jiaotong University. At the end of the course, the evaluation system was used to obtain quantitative comprehensive evaluation results.Results:Based on AHP and FCE models, the evaluation system for ideological and political education in clinical medicine courses was established. The goal was education of students with both medical ethics and skill, the criteria included teachers' ethics, curriculum design, students' experience and development assessment, and thirteen alternatives were used in the system. The implementation effect of ideological and political education in internal medicine course of the first semester in the 2020-2021 academic year was evaluated by the evaluation system. The quantitative comprehensive evaluation score was 4.080 (range 1-5), which showed that the ideological and political education checklist teaching with equal emphasis on medical ethics and skill achieved good educating effect.Conclusion:The evaluation system for the implementation effect of ideological and political education in clinical medicine courses can be constructed based on the AHP and FCE models. The evaluation system is scientific, quantitative, comprehensive, and improvable.

Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Update on salivary gland transplantation in severe dry eye / 中华实验眼科杂志

As a chronic eye disease caused by multiple factors, the treatment of dry eye disease (DED) should be individualized according to the cause and severity of the disease.In patients with severe DED who have lost lacrimal secretion but have not suffered severe damage to the salivary glands, autologous salivary gland transplantation may help bring hope to these patients if conventional treatments are not effective enough.According to the literature, the three major salivary glands and the minor salivary glands have been used as lacrimal gland replacements.Studies have shown that submandibular glands not only have a high gland survival rate after transplantation, but also maintain secretory activity after transplantation and therefore successfully serve as lacrimal gland replacement.During the up to 180-month follow-up period, the subjective symptoms and signs of DED such as dryness, foreign body sensation, and other objective indicators related to DED such as visual acuity and tear film break-up time are effectively improved.Among the minor salivary glands, the labial glands have been proven to maintain secretory function during the up to ten-year follow-up period after transplantation according to the literature, and have therefore become an alternative lacrimal gland replacement.This review summarized the indications, surgical techniques, efficacy evaluation, modulation of salivary flow and complications of the surgery, involving three major salivary glands, parotid, submandibular and sublingual glands, and minor salivary glands among which labial glands are most commonly used.

Clinical value of circadian clock related biomarkers for the diagnosis of chronic pancreatitis with pancreatic exocrine insufficiency / 中华胰腺病杂志

Objective:To examine the expression of core clock genes in the peripheral blood mononuclear cells (PBMCs) and the level of circadian disturbance-related proteins in the serum of chronic pancreatitis (CP) patients with pancreatic exocrine insufficiency (PEI), and explore their potential diagnostic value in clinical practice.Methods:The peripheral blood samples and related clinical data from 68 patients diagnosed with CP in Shanghai General Hospital from Jan 2015 to Jan 2022 were collected. Peripheral blood samples from 30 healthy individuals were used for control. The M-ANNHEIM classification system was used to stratify the clinical stages of patients with CP. The mRNA expression of the core clock genes, including Clock, Bmal1, Per1/2/3 and Cry1/2 in PBMCs was analyzed using realtime qPCR, and the expression of circadian disturbance-related proteins like TrkB, CD 36 and Rbp in serum was measured with ELISA. The receiver operating characteristic curve(ROC) and the area under curve (AUC) was used to test the efficiency for diagnozing PEI. Results:The mRNA expression of Per1 in CP patients was significantly decreased (0.76 vs 1, P<0.05), and the AUC for diagnozing PEI was 0.744 (95% CI 0.628-0.860), with a cut-off value of 0.72; and the sensitivity and specificity was 84.8% and 57.1%, respectively. The protein abundance of serum CD 36 was significantly increased in CP patients (33.85±19.74ng/ml vs 24.71±11.53 ng/ml, P<0.05); the AUC for diagnozing PEI was 0.834 (95% CI 0.735-0.932), with a cut-off value of 29.75 pg/ml; and the sensitivity and specificity was 74.3% and 84.8%, respectively. The expression of CD 36 was increased with the increase of CP clinical stage, and there were statistically significant differences between either two stages (all P value <0.05). The mRNA expression of Per1 in patients with CP in Stage Ⅰ was significantly higher than that in patients with CP in Stage Ⅱ or Ⅲ, and the differences were statistically significant ( P<0.05), but no statistical difference was found between Stage Ⅱ and Stage Ⅲ. Conclusions:The decreased expression of Per1 mRNA in PBMCs and increased level of CD 36 in serum are significantly related to the occurrence of PEI in CP, suggesting that they may have potential value for diagnozing PEI and guiding the clinical practice.

Effects of different auricular point therapies on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy / 针灸推拿医学（英文版）

Objective:To compare the effects of auricular point intradermal needling with auricular point sticking on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy regimens. Methods:Ninety-six patients receiving platinum-based chemotherapy were randomly assigned to three groups using the random number table method,with 32 cases in each group.The control group received conventional nursing care plus 5-hydroxytryptamine receptor antagonist,and the other two groups received additional auricular point intradermal needling or sticking.For the three groups of participants,the acute and delayed vomiting and nausea severity,quality of life,and the additional antiemetic consumption rate were observed. Results:The three groups had no significant differences in the acute vomiting frequency and nausea severity and appetite(P>0.05)but had significant differences in the delayed vomiting frequency and nausea severity(P<0.05);the auricular point intradermal needling group won over the auricular point sticking group.The three groups showed significant differences in comparing the appetite in the delayed stage(P<0.05);both auricular point intradermal needling and sticking groups showed advantages over the control group(P<0.05),but no significant difference existed between the auricular point intradermal needling and sticking groups(P>0.05).There were significant differences in comparing the functional living index-emesis(FLIE)score in both acute and delayed stages among the three groups(P<0.05)and the result favored the auricular point intradermal needling group over the auricular point sticking group(P<0.05).The additional antiemetic consumption rate was higher in the control group than in the other groups(P<0.05). Conclusion:Based on the conventional nursing and 5-hydroxytryptamine receptor antagonist,adding either auricular point intradermal needling or auricular point sticking can lower the vomiting frequency and nausea severity in the delayed stage and improve appetite in patients receiving platinum-based chemotherapy regimen,but they have no notable impact on digestive symptoms in the acute stage;auricular point intradermal needling is superior to auricular point sticking in comparing the overall efficacy.Both auricular point intradermal needling and auricular point sticking can enhance the quality of life in patients undergoing chemotherapy and reduce their additional antiemetic consumption.

Searching for potential biomarkers reflecting early injury and progressive of podocytes in nephropathy based on cellular metabolomics combined with ROC analysis / 药学学报

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Prevention and treatment of lung cancer by regulating tumor-associated macrophages with traditional Chinese medicine / 中国中药杂志

Lung cancer is one of the common malignant tumors in the world, and its incidence and mortality is increasing year by year. Interactions between tumor cells and immune cells in the tumor microenvironment(TME) affect tumor proliferation, infiltration, and metastasis. Tumor-associated macrophages(TAMs) are prominent components of TME, and they have dual regulation effects on malignant progression of lung cancer. The number, activity, and function of M2 macrophages are related to the poor prognosis of lung cancer, and M2 macrophages participate in tumor angiogenesis and immune escape. It has been proved that traditional Chinese medicines(TCMs) and their active ingredients can enhance the antitumor effects, reduce the toxicity of chemotherapy and radiotherapy, and prolong the survival rates of patients with cancer. This paper summarized the role of TAMs in the lung cancer initiation and progression, explored the molecular mechanism of TCM in regulating the recruitment, polarization phenotype, activity, and expression of related factors and proteins of TAMs, and discussed related signal pathways in the prevention and treatment of lung cancer based on the TCM theory of "reinforcing healthy qi and eliminating pathogen". This paper is expected to provide new ideas for the immunotherapy of targeted TAMs.

Research progress in targeting autophagy of traditional Chinese medicine and natural compounds to regulate atherosclerosis / 中国中药杂志

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.

Reinforced radiculoplasty for the treatment of symptomatic sacral Tarlov cysts: A clinical analysis of 71 cases / 北京大学学报(医学版)

OBJECTIVE@#To investigate the safety and efficacy of reinforced radiculoplasty in the treatment of symptomatic sacral Tarlov cysts (TCs).@*METHODS@#A retrospective analysis was performed on the clinical data and follow-up data of 71 patients with symptomatic sacral TCs who underwent reinforced radiculoplasty in the Neurosurgery Department of Peking University Third Hospital from June 2018 to March 2021. All the operations were performed under neuroelectrophysiological monitoring. Intraoperative cyst exploration, partial resection of the cyst wall, narrowing of the leak, nerve root sleeve radiculoplasty and artificial dural reinforcement were performed. The incidence of postoperative complications and new neurological dysfunction was analyzed. Visual analogue scale (VAS) was used to assess the changes of pain before and after surgery. The Japanese Orthopedics Association (JOA) low back pain score was used to evaluate the changes in nerve function before and after surgery.@*RESULTS@#In the study, 71 patients had 101 TCs, 19 (18.8%) TCs originated from the left S1 nerve, 26 (25.7%) originated from the left S2 nerve, 3 (3.0%) originated from the left S3 nerve, 14 (13.9%) originated from the right S1 nerve, 33 (32.7%) originated from the right S2 nerve, 6 (5.9%) originated from the right S3 nerve, all the TCs underwent reinforced radiculoplasty. Deep infection (1 case), subcutaneous effusion (1 case), fat li-quefaction (1 case) and urinary tract infection (4 cases) were recorded postoperatively. The patients were followed up for 12-43 months (median, 26 months). Two cases had new urinary retention after operation, and the catheter was removed at the end of the first and second months respectively. One case had new fecal weakness, which improved after 3 months. Compared with preoperation, VAS decreased significantly at the last follow-up [median, 6 (4-9) vs. 1 (0-5), Z=-7.272, P < 0.001], JOA score increased significantly [median, 20 (16-25) vs. 27 (18-29), Z=-7.265, P < 0.001]. There were 18 cured cases (25.4%), 41 excellent cases (57.7%), 8 effective cases (11.3%), and 4 invalid cases (5.6%). The total efficiency was 94.4% (67/71). Two (1.98%) cysts recurred.@*CONCLUSION@#For patients with symptomatic sacral TCs, reinforced radiculoplasty can significantly improve the pain and nerve function, which is safe and reliable.

Functional characterization and enzymatic properties of flavonoid glycosyltransferase gene CtUGT49 in Carthamus tinctorius / 中国中药杂志

Carthami Flos, as a traditional blood-activating and stasis-resolving drug, possesses anti-tumor, anti-inflammatory, and immunomodulatory pharmacological activities. Flavonoid glycosides are the main bioactive components in Carthamus tinctorius. Glycosyltransferase deserves to be studied in depth as a downstream modification enzyme in the biosynthesis of active glycoside compounds. This study reported a flavonoid glycosyltransferase CtUGT49 from C. tinctorius based on the transcriptome data, followed by bioinformatic analysis and the investigation of enzymatic properties. The open reading frame(ORF) of the gene was 1 416 bp, encoding 471 amino acid residues with the molecular weight of about 52 kDa. Phylogenetic analysis showed that CtUGT49 belonged to the UGT73 family. According to in vitro enzymatic results, CtUGT49 could catalyze naringenin chalcone to the prunin and choerospondin, and catalyze phloretin to phlorizin and trilobatin, exhibiting good substrate versatility. After the recombinant protein CtUGT49 was obtained by hetero-logous expression and purification, the enzymatic properties of CtUGT49 catalyzing the formation of prunin from naringenin chalcone were investigated. The results showed that the optimal pH value for CtUGT49 catalysis was 7.0, the optimal temperature was 37 ℃, and the highest substrate conversion rate was achieved after 8 h of reaction. The results of enzymatic kinetic parameters showed that the K_m value was 209.90 μmol·L~(-1) and k_(cat) was 48.36 s~(-1) calculated with the method of Michaelis-Menten plot. The discovery of the novel glycosyltransferase CtUGT49 is important for enriching the library of glycosylation tool enzymes and provides a basis for analyzing the glycosylation process of flavonoid glycosides in C. tinctorius.

Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-β and Prevents Alzheimer's Disease-Type Pathology and Cognitive Deficits / 神经科学通报·英文版

Deficiencies in the clearance of peripheral amyloid β (Aβ) play a crucial role in the progression of Alzheimer's disease (AD). Previous studies have shown that the ability of blood monocytes to phagocytose Aβ is decreased in AD. However, the exact mechanism of Aβ clearance dysfunction in AD monocytes remains unclear. In the present study, we found that blood monocytes in AD mice exhibited decreases in energy metabolism, which was accompanied by cellular senescence, a senescence-associated secretory phenotype, and dysfunctional phagocytosis of Aβ. Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβ in vivo and in vitro. Moreover, enhancing blood monocyte Aβ phagocytosis by improving energy metabolism alleviated brain Aβ deposition and neuroinflammation and eventually improved cognitive function in AD mice. This study reveals a new mechanism of impaired Aβ phagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

Killing effect of anti-MSLN-iCAR-NK cells derived from induced pluripotent stem cells on ovarian epithelial cancer cells / 中华妇产科杂志

Objective: To investigate the cytotoxic effects of induced pluripotent stem (iPS) cells of anti-mesothelin (MSLN)-chimeric antigen receptor natural killer (CAR-NK) cells (anti-MSLN-iCAR-NK cells) on ovarian epithelial cancer cells. Methods: Twenty cases of ovarian cancer patients who underwent surgical treatment at Henan Provincial People's Hospital from September 2020 to September 2021 were collected, and 20 cases of normal ovarian tissues resected during the same period due to other benign diseases were also collected. (1) Immunohistochemistry and immunofluorescence were used to verify the expression of MSLN protein in ovarian cancer tissues. (2) Fresh ovarian cancer tissues were extracted and cultured to obtain primary ovarian cancer cells. Recombinant lentiviral vectors targeting anti-MSLN-CAR-CD244 were constructed and co-cultured with iPS cells to obtain anti-MSLN-iCAR cells. These cells were differentiated into anti-MSLN-iCAR-NK cells using cytokine-induced differentiation method. The cell experiments were divided into three groups: anti-MSLN-iCAR-NK cell group, natural killer (NK) cell group, and control group. (3) Flow cytometry and live cell staining experiment were used to detect the apoptosis of ovarian cancer cells in the three groups. (4) Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), granzyme B (GZMB), perforin 1 (PRF1), interleukin (IL)-6, and IL-10 in the three groups of ovarian cancer cells. Results: (1) Immunohistochemistry analysis showed that a positive expression rate of MSLN protein in ovarian cancer tissues of 65% (13/20), while normal ovarian tissues had a positive rate of 30% (6/20). The comparison between the two groups was statistically significant (χ2=4.912, P=0.027). Immunofluorescence analysis revealed that the positive expression rate of MSLN protein in ovarian cancer tissues was 70% (14/20), while normal ovarian tissues had a positive rate of 30% (6/20). The comparison between the two groups was statistically significant (χ2=6.400, P=0.011). (2) Flow cytometry analysis showed that the apoptotic rate of ovarian cancer cells in the anti-MSLN-iCAR-NK cell group was (29.27±0.85)%, while in the NK cell group and control group were (8.44±0.34)% and (6.83±0.26)% respectively. There were statistically significant differences in the comparisons between the three groups (all P<0.01). Live cell staining experiment showed that the ratio of dead cells to live cells in the anti-MSLN-iCAR-NK cell group was (36.3±8.3)%, while in the NK cell group and control group were (5.4±1.4)% and (2.0±1.3)% respectively. There were statistically significant differences in the comparisons between the three groups (all P<0.001). (3) ELISA analysis revealed that the expression levels of IFN-γ, TNF-α, GZMB, PRF1, IL-6, and IL-10 in ovarian cancer cells of the anti-MSLN-iCAR-NK cell group were significantly higher than those in the NK cell group and the control group (all P<0.05). Conclusion: The anti-MSLN-iCAR-NK cells exhibit a strong killing ability against ovarian cancer cells, indicating their potential as a novel immunotherapy approach for ovarian cancer.

Research progress on potential therapeutic targets of chronic cough / 中国药理学通报

Chronic cough is caused by low levels of heat, mechanical or chemical exposure, which is characterized by the disorders of channels and receptors in neuroregulation such as the peripheral and central nerves. Potential regulatory targets of peripheral nerves include P2X3 receptors and transient receptor potential channels, while potential regulatory targets of central nerves include voltage-gated sodium channels, neurokinin-1 receptors, α-7acetylcholine receptors and gamma aminobutyric acid receptors. This paper focuses on the principle and clinical research evidence of several ongoing targeted therapy strategies, in order to provide new ideas for the development of drugs for the treatment of chronic cough.