Dendrobii Caulis Mixture-containing Serum Protects Mice from Podocyte Injury Induced by High Glucose / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Dendrobium mixture （DMix）-containing serum on high glucose-induced podocyte injury in mice. MethodThe MPC5 mouse glomerular podocytes were cultured in vitro， and the optimal glucose concentration for modeling， modeling time， and concentration of DMix-containing serum for administration were determined. The cells were classified into normal （5.5 mmol·L-1 glucose+10% blank serum）， model （30 mmol·L-1 glucose+10% blank serum）， DMix-containing serum （30 mmol·L-1 glucose+10% DMix-containing serum）， ferroptosis inhibitor （Fer-1， 30 mmol·L-1 glucose+10% blank serum+1 μmol·L-1 Fer-1） groups. The corresponding kits were used to measure the levels of Fe2+ and lactate dehydrogenase （LDH） in cells. Enzyme-linked immunosorbent assay was employed to determine the content of glutathione （GSH） and lipid peroxide （LPO） in cells. Fluorescence probe was used to measure the reactive oxygen species （ROS） level. Real-time fluorescence quantitative polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Wilms' tumor-1 （WT-1）， desmin， long chain acyl-CoA synthase 4 （ACSL4）， and glutathione peroxidase 4 （GPX4） in podocytes. ResultCompared with the blank group， the intervention with 30 mmol·L-1 glucose for 48 h reduced podocyte viability （P<0.01）， and the 10% DMix-containing serum showed the most significant improvement in podocyte viability （P<0.01）. Compared with the normal group， the model group presented elevated levels of Fe2+， LDH， LPO， and ROS， lowered GSH level， up-regulated mRNA and protein levels of desmin and ACSL4， and down-regulated mRNA and protein levels of WT-1 and GPX4 （P<0.01）. Compared with the model group， the DMix-containing serum lowered the Fe2+， LDH， LPO， and ROS levels， elevated the GSH level， down-regulated the mRNA and protein levels of desmin and ACSL4， and up-regulated the mRNA and protein levels of WT-1 and GPX4 in podocytes （P<0.05， P<0.01）. ConclusionDMix-containing serum exerts a protective effect on high glucose-induced podocyte injury by inhibiting ferroptosis.

Signal mining and analysis of selinexor adverse events / 中国药房

OBJECTIVE To mine the adverse drug event （ADE） signals of selinexor， and to provide reference for its clinical safety medication. METHODS ADE data for selinexor reported from July 3rd， 2019 to March 31st， 2023 were collected from the FDA adverse event reporting system （FAERS）. Data mining was performed by using the reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods， and categorization statistics were performed by using the system organ class （SOC） and preferred term （PT） from drug ADE terminology set in the MedDRA （version 26.0）. RESULTS A total of 3 084 ADE reports were obtained for selinexor， with a total of 134 ADE-positive signals. Among the reported genders， there were 127 males and 124 females， with a predominant age of ≥65 years old （4.12%）； the United States had the highest number of reports （96.53%）， with consumers being the main reporters （77.27%）； severe ADR was mainly characterized by hospitalization/prolonged hospitalization （26.26%）， followed by death （17.15%）. The top 3 ADE in the list of frequency were nausea （1 162 times）， fatigue （790 times） and anorexia （610 times）， all of which were mentioned in the selinexor’s instructions. The top 3 signals in the list of strength were device-associated bacteremia （ROR＝115.07， PRR＝114.94）， blepharospasm dysfunction （ROR＝106.70， PRR＝106.54）， and salmonella sepsis （ROR＝99.90， PRR＝99.81）， all of which were not mentioned in the selinexor’s instructions. CONCLUSIONS In addition to the ADE of nausea mentioned in the instruction manual， attention should also paid to device-associated bacteremia， blepharospasm dysfunction， salmonella sepsis， and other ADE not mentioned in the instruction manual when using selinexor in clinical practice； weekly rechecking of the patient’s blood routine should be done to monitor the patient’s blood indexes， symptoms of infection， and so on， to ensure that the safety of 1661962346@qq.com drug use.

Differences in Clinical Characteristics and Surgical Outcomes of Patients with Ischemic and Hemorrhagic Pituitary Adenomas

Objective@#: Ischemia and hemorrhage of pituitary adenomas (PA) caused important clinical syndrome. However, the differences on clinical characteristics and surgical outcomes between these two kinds apoplexy were less reported. @*Methods@#: A retrospective analysis was made of patients with pituitary apoplexy between January 2013 and June 2018. Baseline and clinical characteristics before surgery were reviewed. All patients underwent transsphenoidal surgery and were followed up at least 1 year. @*Results@#: Total 67 cases (5.8%) among 1147 pituitary tumor patients were enrolled, which consisted of 28 (~2.4%) ischemic PA and 39 (~3.4%) hemorrhagic PA. There were more male patients in the ischemic group compared with hemorrhagic group (78.6% vs 53.8%, p=0.043). However, the mean age, tumor size and functional tumor ratio were significant higher in the hemorrhagic group. Headache was more common in ischemic PA (82.1%) than that of hemorrhagic PA (51.3%, p=0.011). Magnetic resonance imaging findings found that mucosal thickening and enhancement of the sphenoid sinus was observed in 15 ischemic PA patients (n=27, 55.6%), but none in patients with hemorrhagic PA (n=38, p<0.0001). It was worth noting that the rate of pre-surgical hypopituitarism in ischemic PA patients were seemed higher than that in hemorrhagic PA patients, but not significant. The two groups got a total tumor resection rate at 94.1% and 92.9%, independently. No significant difference on the operative time, blood loss in operation and complications in perioperative period was observed in two groups. After operation, cranial nerve symptoms recovered to normal at 81.8% of ischemic PA patients and 82.6% of hemorrhagic PA patients. Importantly, the incidence of postoperative hypopituitarism partially decreased in both groups, among which the rate of hypothyroidism in ischemic PA patients significantly decreased from 46.4% to 18.5% (p=0.044). @*Conclusion@#: Patients with ischemic PA presented different clinical characteristics to the hemorrhagic ones. Transsphenoidal surgery should be considered for the patients with neuro-ophthalmic deficits and might benefit for pituitary function recovery of the apoplectic adenoma patients, especially pituitary thyroid axis in ischemic PA patients.

Study on in vitro differentiation of human adenoid-derived mesenchymal stem cells into olfactory sensory neurons / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility of isolation and culture of human adenoid-derived mesenchymal stem cells (aMSCs) in vitro, and to observe the differentiation of aMSCs into olfactory sensory neurons. Methods: Adenoid tissues surgically removed from children with adenoid hypertrophy in the Second Xiangya Hospital of Central South University from September to November of 2020 were collected. The adenoid tissues were digested and isolated by trypsin and then cultured with adhesion method. The expressions of cell surface antigens CD45, CD73 and CD90 on aMSCs of P5 generation were tested by flow cytometry, and the ability of osteogenic and adipogenic induction were used to identify cell differentiation ability. Then, aMSCs were induced into differentiation by retinoic acid (RA), sonic hedgehog (SHH), basic fibroblast growth factor (bFGF), RA+SHH, RA+bFGF, SHH+bFGF and RA+SHH+bFGF, respectively. The morphology of differentiated cells was observed under inverted microscope. The expression of β-tubulin 3, which was the specific marker of sensory neuron, the expressions of growth associated protein-43 (GAP43) and olfactory maker protein (OMP), which were the specific markers of olfactory sensory neuron, were detected by immunofluorescence antibody assay. The expression intensities were compared by Chi-square test of four-grid table data. Results: aMSCs were successively isolated and cultured from human adenoid tissues. P0 cells generation had good adhesion and proliferation performance. P2 cells were basically purified. P5 cells expressed CD73 and CD90 with the purity of 99.3% and 99.75% respectively, without CD45 expression. P5 cells had a good ability of osteogenic differentiation and adipogenic differentiation. Neuron-like morphology and expression of β-tubulin 3 were found in differentiated cells after induced by RA, SHH, or bFGF, respectively. An induction of expression of GAP43 was found in differentiated cells of bFGF+SHH group and RA+SHH+bFGF group, without expression of OMP of each group. The intensity of GAP43 expression of RA+SHH+bFGF group was stronger than that of bFGF+SHH group (χ2=17.48, P<0.005). Conclusions: aMSCs can be cultured from human adenoid tissues, with the stably passaged and good differentiation ability. As a new population of mesenchymal stem cells, aMSCs have the neuroregenerative properties and could differentiate into immature olfactory sensory neurons under the induction of RA+SHH+bFGF in vitro.

The experience and enlightenment of robotic surgery training course in the University of Pittsburgh Medical Center / 中华医学教育探索杂志

Objective:To introduce the experience of robotic surgery training course in the University of Pittsburgh Medical Center.Methods:The specific process of the training course was introduced in detail, and the results of the training course were summarized and analyzed. A total of 15 surgeons completed the first step of the training (operation table simulation training), 14 (93.3%) completed the second step (pancreatoduodenectomy tissue anastomosis simulation training), and 196 cases of tissue anastomosis simulation training were completed. Statistical analysis was performed using STATA and SPSS software. Wilcoxon rank sum test was used to analyze the data.Results:The average scores of the surface validity Likert scale for anastomosis simulation training were: (15/20) for Pancreaticojejunostomy (PJ), (15/20) for Gastrojejunostomy (GJ), and (17/20) for Hepatocholangiojejunostomy (HJ). In the PJ and GJ simulation training, compared with the gold standard, the error rate and OSATS score were significantly improved ( P > 0.05), and the operation time was not significantly reduced ( P < 0.05). In HJ simulation training, the error rate, OSATS score and operation time did not show significant improvement ( P < 0.05). However, it could be concluded that all the simulation operations performed by the trainees after the training were better than the first time, when linear regression and quadratic fitting models were performed to analyze continuous trainings of the trainees as a group. Conclusion:The training course carried out by the University of Pittsburgh Medical Center is valid and effective, and it can be used for reference to explore a way for the development of robotic surgery fitting to the real conditions of our country.

PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats / 药物分析学报

Epidemiological and animal studies indicate that pre-existing diabetes increases the risk of Parkinson's disease(PD).However,the mechanisms underlying this association remain unclear.In the present study,we found that high glucose(HG)levels in the cerebrospinal fluid(CSF)of diabetic rats might enhance the effect of a subthreshold dose of the neurotoxin 6-hydroxydopamine(6-OHDA)on the development of motor disorders,and the damage to the nigrostriatal dopaminergic neuronal pathway.In vitro,HG promoted the 6-OHDA-induced apoptosis in PC12 cells differentiated to neurons with nerve growth factor(NGF)(NGF-PC12).Metabolomics showed that HG promoted hyperglycolysis in neurons and impaired tricarboxylic acid cycle(TCA cycle)activity,which was closely related to abnormal mito-chondrial fusion,thus resulting in mitochondrial loss.Interestingly,HG-induced upregulation of pyruvate kinase M2(PKM2)combined with 6-OHDA exposure not only mediated glycolysis but also promoted abnormal mitochondrial fusion by upregulating the expression of MFN2 in NGF-PC12 cells.In addition,we found that PKM2 knockdown rescued the abnormal mitochondrial fusion and cell apoptosis induced by HG+6-OHDA.Furthermore,we found that shikonin(SK),an inhibitor of PKM2,restored the mito-chondrial number,promoted TCA cycle activity,reversed hyperglycolysis,enhanced the tolerance of cultured neurons to 6-OHDA,and reduced the risk of PD in diabetic rats.Overall,our results indicate that diabetes promotes hyperglycolysis and abnormal mitochondrial fusion in neurons through the upre-gulation of PKM2,leading to an increase in the vulnerability of dopaminergic neurons to 6-OHDA.Thus,the inhibition of PKM2 and restoration of mitochondrial metabolic homeostasis/pathways may prevent the occurrence and development of diabetic PD.

Analysis and Promotion Strategy of Medical Students’ Mental Health Status Based on Healthy Personality Orientation / 中国医学伦理学

To understand the positive mental health status of medical students, improve their mental health level, and cultivate medical talents with sound personality and all-round development. Starting from the positive psychological health concept of healthy personality orientation, the Mental Health Scale with a Healthy Personality Orientation for College Students was used to conduct a random sampling survey on 600 medical students in a medical college. The results showed that the mental health score of medical students was (90.13±15.01), which was lower than that of national college students, and their difference was statistically significant (P=0.001). Medical students scored significantly lower than national college students in the three dimensions of happiness experience (P<0.001), interpersonal harmony (P=0.003), and goal pursuit (P=0.008). Moreover, there were group differences in the level and structure of mental health among medical students of different genders, grades, majors, and family origins (P<0.05). Universities should adopt targeted educational measures for different groups of medical students to guide them to cultivate positive psychological qualities and promote their physical and mental health development.

Clinicopathological Analysis and Treatment of Adult Patients with Inflammatory Myofibroblastic Tumor: A 15-Year Single- Center Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. @*Materials and Methods@#We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. @*Results@#Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. @*Conclusion@#Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Analysis of pathogenic characteristics of enteroaggregative Escherichia coli in children with diarrhea in Shanghai from 2019 to 2021 / 上海预防医学

ObjectiveTo understand the presence of virulence genes， molecular typing characteristics， and antibiotic sensitivity of enteroaggregative Escherichia coli （EAEC） in children with diarrhea in Shanghai， so as to provide a scientific basis for EAEC monitoring and standardized treatment of EAEC infection. MethodsEAEC strains isolated from children （≤5 years old） with diarrhea in six districts of Shanghai were collected as the study subjects. EAEC virulence genes were detected by real-time fluorescence quantitative PCR， molecular typing was performed by pulsed-field gel electrophoresis （PFGE）， and drug susceptibility tests were conducted using the microbroth dilution method. χ2 test and two independent samples t-test were used to compare the differences in virulence genes and antibiotic resistance between suburban and urban EAEC strains. ResultsFrom 2019 to 2021， the overall detection rates of gene aggR， pic and astA of 59 EAEC were 30.5%， 50.8%， and 57.6%， respectively. There was no significant difference in the detection rates of virulence genes between suburban and urban EAEC strains （P>0.05）. PFGE analysis revealed that only two EAEC strains belonged to the same PFGE pattern and were collected from the same hospital， and the overall PFGE patterns were polymorphic. EAEC showed susceptibility to imipenem and colistin E， and the resistance rates to sulfamethoxazole （SXT）， ampicillin （AMP）， nalidixic acid （NAL）， and tetracycline （93.1%， 79.3%， 63.8%， and 58.6%， respectively） were higher than 50.0%. The antibiotic resistance rates of cefazolin （CFZ）， cefotaxime （CTX）， and ciprofloxacin （CIP） were significantly different between EAEC strains from suburban and urban areas （P<0.05）. A total of 47 strains exhibited multi-drug resistance， with the most common resistance spectrum being AMP-SXT-NAL. There was no statistically significant difference in the number of multidrug-resistant EAEC strains between suburban and urban areas （P>0.05）. ConclusionThe EAEC virulence gene assemblages in children with diarrhea in the six districts of Shanghai are diverse， and the molecular typing patterns are relatively scattered， indicating possible cross-infection of homologous strains. Multi-drug resistance in EAEC strains is relatively common， and there is a statistically significant difference in the resistance rates of CFZ， CTX and CIP between urban and suburban EAEC strains. Attention should be given to standardizing the use of clinical antibiotics to effectively control the dissemination of multidrug-resistant EAEC strains.

Research progress of effect of gut microbiota on non-small cell lung cancer / 中国胸心血管外科临床杂志

@#The human gut microbiota regulates many host pathophysiological processes including metabolic, inflammatory, immune and cellular responses. In recent years, the incidence and mortality of lung cancer have increased rapidly, which is one of the biggest challenges in the field of cancer treatment today, especially in non-small cell lung cancer. Animal models and clinical studies have found that the gut microbiota of non-small cell lung cancer patients is significantly changed compared with the healthy people. The gut microbiota and metabolites can not only play a pro-cancer or tumor suppressor role by regulating immune, inflammatory responses and so on, but also be related with radiotherapy and chemotherapy of non-small cell lung cancer and the resistance of immunotherapy. Therefore, gut microbiota and related metabolites can be both potential markers for early diagnosis and prognosis in patients with non-small cell lung cancer and novel therapeutic targets for targeted drugs. This study will review the latest research progress of effect of gut microbiota on non-small cell lung cancer, and provide a new diagnosis and treatment ideas for non-small cell lung cancer.

Prognostic factors of spontaneous rupture hemorrhage in primary liver cancer / 中华肝胆外科杂志

Objective:To explore the independent influencing factors of patients with spontaneous rupture hemorrhage of primary liver cancer (PLC).Methods:A retrospective cohort study was conducted. The clinical data of 128 patients with PLC spontaneous rupture hemorrhage in Ningxia Medical University General Hospital from January 2017 to March 2022 were analyzed, including 108 males and 20 females, aged (53.4±10.6) years. According to different treatment, 128 patients were divided into liver resection group (LR, n=28), interventional group [ n=39, transcatheter arterial chemoembolization (TACE) and transcatheter arterial embolization (TAE)], and conservative group ( n=61). Univariate and multivariate Cox regression was performed to analyze prognostic factors. The LR and TACE groups were subdivided into LR (aLR, n=15), TACE/TAE (aTACE, n=33) and LR+ TACE ( n=19) groups. Kaplan-Meier analysis was performed, and the survival rate was compared by log-rank test. Results:The median survival time of LR group and TACE group was 23 months and 21 months, respectively, with no statistical significance ( P>0.05). The median survival time (38 months) in LR+ TACE group was significantly longer than that in aLR group (10 months) and aTACE group (9 months), and the difference was statistically significant ( P<0.05). Univariate analysis showed that Barcelona Clinical Liver Cancer (BCLC)staging, tumor length ≥10.0 cm, vascular invasion, α-fetoprotein ≥400 μg/L, total bilirubin, prothrombin time and treatment affected overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Multivariate analysis showed that BCLC staging, tumor length ≥10.0 cm, Child-Pugh grade and treatment were independent influencing factors for overall survival of PLC spontaneous rupture hemorrhage patients (all P<0.05). Conclusion:BCLC stage, tumor length ≥10.0 cm, Child-Pugh grade and treatment method are independent predictors of overall survival in patients with spontaneous rupture of PLC. LR combined with TACE therapy can improve the survival and prognosis of patients with spontaneous rupture of primary liver cancer.

Construction of a High-Throughput Mutation Library of Mycobacterium Rifampin Resistance Gene rpoB / 中山大学学报(医学科学版)

ObjectiveTo establish a mutation library of rifampicin resistance gene rpoB. MethodsThe ΔrpoB attB：：rpoB strain of Mycobacterium smegmatis （M. smegmatis） be constructed by homologous recombination and L5 attB phage integration site exchange. Based on the L5 attB plasmid exchange system and resistance selection medium， 48 clones are selected to verify plasmid replacement efficiency. Degenerate primers are designed every 3 bases in the rifampicin resistance determining region （RRDR）， and a full-coverage mutation library of 81 bases in RRDR region is obtained by PCR amplification. The library fragments are seamlessly cloned into the vector and transformed into Escherichia coli （E. coli）to form an E. coli mutation library. Based on the principle of plasmid exchange， the mutant plasmid library is transformed into the M. smegmatis strain ΔrpoB attB：：rpoB， and the original L5 attB site plasmid is replaced to form the M. smegmatis mutant library. The genotype of the library are determined by genome extraction， library construction and high-throughput sequencing. ResultsCompared with the wild-type rpoB gene （5 600 bp）， the amplified fragment of the rpoB knockout strain is 2 200 bp， which proved that the ΔrpoB attB：：rpoB conditional knockout strain of M. smegmatis is successfully constructed. The success rate of plasmid replacement is 100%. There were 540 kinds of single amino acid mutations in both E. coli library and M. smegmatis library， 5 301 kinds of multi-point mutations in E. coli library， and 853 kinds of multi-point mutations in M. smegmatis library. The correlation coefficient between E. coli library and M. smegmatis library is 0.84. ConclusionsWe have developed a strategy to construct a library of mutants targeting the essential mycobacterial gene rpoB， and successfully established a mutant library of rifampicin resistance gene rpoB.

Contamination status and molecular typing of Legionella pneumophila in artificial water environment in Shanghai hospitals from 2019 to 2020 / 环境与职业医学

Background The incidence of Legionnaires' disease is increasing globally and artificial water environment is becoming a common source of outbreaks. Molecular typing techniques can help prevent and control Legionella. Objective To understand the molecular epidemiological characteristics of Legionella pneumophila in artificial water environment of Shanghai hospitals, and provide a scientific basis for the prevention and control of Legionnaires' disease. Methods Water samples were collected from artificial water environment in 14 hospitals from May to October each year from 2019 to 2020 in Shanghai. A total of 984 water samples were collected from 8 Grade-A tertiary hospitals and 6 non-Grade-A tertiary hospitals, including 312 samples of cooling water, 72 samples of chilled water, and 600 samples of tap water. The water samples were isolated and serotyped for Legionella pneumophila and preserved, and the positive rate of Legionella pneumophila in the samples was used as an indicator of contamination. The preserved strains were resuscitated and 81 surviving strains were obtained for pulsed field gel electrophoresis (PFGE) typing analysis. Results A total of 124 Legionella pneumophila positive water samples were detected, with a positive rate of 12.60%. The positive rate was higher in the Grade-A tertiary hospitals (16.54%, 87/526) than in the non-Grade-A tertiary hospitals (8.08%, 37/458) (χ2=15.91, P<0.001). The positive rate of cooling water (23.40%) was the highest among different types of water samples, and the difference was statistically significant (χ2=61.19, P<0.001). The difference in positive rate of tap water was statistically significant among different hospital departments (χ2=11.37, P<0.05). The positive rate in 2019 (15.06%) was higher than that in 2020 (9.84%) (χ2=6.23, P<0.05). From May to October, August had the highest annual average positive rate (16.46%) and October had the lowest (8.54%), but the difference in positive rates among months was not statistically significant (χ2=5.39, P=0.37). The difference in positive rate among districts was statistically significant (χ2=24.88, P<0.001). A total of 131 strains of Legionella pneumophila were isolated, with serotype 1 (80.15%, 105/131) predominating. Among the 81 surviving strains of Legionella pneumophila subjected to PFGE typing, the band-based similarity coefficients ranged from 41.30% to 100%. Among the 29 PFGE band types (S1-S29) recorded, each band type included 1-10 strains, and S28 was the dominant band type. Four clusters (I-IV) of PFGE band types were identified, accounting for 66.67% (54/81) of all strains and containing 13 band types. Conclusion Legionella pneumophila contamination is present in the artificial water environment of hospitals in Shanghai from 2019 to 2020, and the contamination in tap water deserves attention. The detected serotype of Legionella pneumophila is predominantly type 1, and PFGE typing reveals the presence of genetic polymorphism. Therefore, the monitoring and control of Legionella pneumophila in hospital artificial water environment should be strengthened.

Research progress of furmonertinib for EGFR-mutated non-small cell lung cancer / 中国药房

Lung cancer is mainly non-small cell lung cancer （NSCLC）. NSCLC is often associated with epidermal growth factor receptor （EGFR） gene mutations. Currently， epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） are the preferred first-line treatment option for EGFR-mutated NSCLC. Furmonertinib is the second third-generation EGFR-TKI marketed in China， which is developed independently by China. In this review， it is found that furmonertinib has dual activity， strong tumor suppression， high selectivity， and high safety profile， and is effective in the treatment of EGFR-sensitive mutation， EGFR exon 20 T790M resistance mutation， EGFR exon 20 insertion mutation， and central nervous system metastasis NSCLC， and its relevant clinical trials are only enrolled in Chinese patients， which is more guidance for Chinese NSCLC patients in China.

Quality evaluation of Qilong Zhuang'er oral liquid based on UHPLC-Q-exactive orbitrap MS and chemometrics analysis / 药学学报

An UHPLC-Q-exactive orbitrap MS method for the simultaneous determination of 19 chemical components in Qilong Zhuang'er oral liquid was established and the quality differences between different batches of samples was compared by chemometric analysis to provide a basis for the quality evaluation of the preparation. The contents of allantoin, L-proline, pyroglutamic acid, hordenine, adenosine, L-phenylalanine, guanosine, L-tryptophan, caffeic acid, calycosin-7-glucoside, verbascoside, isoacteoside, ononin, calycosin, 3-hydroxy-9,10-dimethoxyptercarpan, formononetin, atractylenolide III, atractylenolide II and astragaloside A were analyzed by cluster heat map, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) using Hiplot platform and MarkerlynxXS software to comprehensively evaluate the quality difference of different batches of Qilong Zhuang'er oral liquid. The 19 chemical compounds showed good linearity in their respective concentration ranges (r ≥ 0.999). The RSD of precision, repeatability and stability (24 h) tests were all less than 1.94%. The average recovery was 97.24%-102.75% (RSD < 2.74%, n = 6). The 10 batches of samples were divided into two categories by cluster heat map and PCA analysis. 3-Hydroxy-9,10-dimethoxyptercarpan, atractylenolide III, calycosin, atractylenolide II, formononetin, allantoin and caffeic acid were identified as differential markers by PLS-DA. The established multi component quantitative method of Qilong Zhuang'er oral liquid combined with chemometric analysis can provide reference for the quality evaluation of the preparation.

Developing a development index system of Shanghai district-level disease prevention and control institutions using the Delphi method / 上海预防医学

ObjectiveTo construct an evaluation index system for the development of district-level disease prevention and control centers according to the requirements of the modernization of Shanghai’s disease control system and public health work practices， and to comprehensively assess the construction and development of district-level disease prevention and control institutions. MethodsAccording to the national and municipal requirements for the development of disease prevention and control institutions， an index framework was proposed through literature search and expert interviews. 39 representative experts in the field of public health at the national， provincial， and municipal （district） levels were selected to participate in the consultation and construction of the index system. The authority coefficient， the coefficient of variation， etc. were used to carry out quality control and determination of each index on the Delphi method. ResultsThe questionnaire response rate was 100%， the expert authority coefficient was 0.86，the degree of familiarity was 0.79， and the judgment basis was 0.92. The coefficients of variation of the necessary indicators in the index system were all <0.25 in the dimension of importance， and there were statistical differences in the statistical test of Kendall’s W coordination coefficients at all levels and dimensions （all P<0.001）. After multiple rounds of consultation， experts reached a consensus， forming a development evaluation index system of district-level CDCs with 6 first-level indicators， 24 second-level indicators， and 105 third-level indicators （including 63 necessary indicators and 42 recommended indicators）. ConclusionThe evaluation index system of Shanghai district-level CDCs based on the Delphi method has good authority， reliability， sensitivity and operability. This indicator system can effectively support the development of Shanghai district-level CDCs， and can be used for evaluation at multiple levels and in an all-round way in the future. The evaluation results can provide an evidence-based basis for the modernization of the disease prevention and control system and the continuous and dynamic updating of the development goals in the future.

Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy / 中华胃肠外科杂志

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

Pathological features of early gastric cancer and its background mucosa after eradication of Helicobacter pylori and their implications for biopsy diagnosis / 中华病理学杂志

Objective: To investigate the clinicopathological changes of early gastric cancer, especially its background mucosa, after the eradication of Helicobacter pylori (H. pylori), and to investigate the causes of underdiagnosis in preoperative biopsy pathology. Methods: Ninety cases of early gastric cancer after H. pylori eradication and 120 cases of endoscopic submucosal dissection (ESD) specimens without H. pylori eradication and their corresponding biopsy specimens were collected from Beijing Friendship Hospital Affiliated to Capital Medical University during 2016-2021. The clinicopathological data of the patients were analyzed, and the histopathological characteristics and immunophenotypic results compared. Results: Compared with the early gastric cancer without H. pylori eradication history, the histopathological type of early gastric cancer after H. pylori eradication was differentiated adenocarcinoma, with staggered distribution of cancerous and non-cancerous epithelium in the tumor area. The morphologic characteristics of gastric mucosa in the background of early gastric cancer after H. pylori eradication, were distinctive, including widening of the opening of enterosylated glandular ducts, serrated change of luminal margin, eosinophilic and microvesicular cytoplasm of enterosylated epithelium. Low-grade atypia existed in gastric cancer epithelial cells after sterilization, which might lead to underdiagnosis or missed diagnosis in biopsy pathology. Conclusions: Early gastric cancer and its background mucosa after H. pylori eradication have unique morphological characteristics, which can be used as a clue for pathological diagnosis, improve the accuracy of biopsy pathology and reduce the underdiagnosis.

Research on hypoglycemic activity of Osmanthus fragrans var. thunbergii extract / 药学学报

This study aimed to assess the hypoglycemic activity, and in vitro inhibition of α-glucosidase, inhibition of the advanced glycation end products (AGEs), and total antioxidant capacity were used to clarify its bioactivity. Furthermore, the potential hypoglycemic active chemical constituents in the aqueous extract of Osmanthus fragrans var. thunbergii flower were characterized using high performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) method. The result showed that in vitro inhibition of α-glucosidase of the extract (IC50 = 2.11 ± 0.26 mg·mL-1) were similar to acarbose (IC50 = 2.88 ± 0.32 mg·mL-1), and it inhibited the AGEs formation and the total antioxidant capacity in a certain extent. Based on the MS fragmentation pathway analysis of reference chemical acteoside contained in this extract, and related references, 73 constituents were tentatively identified from the aqueous extract of Osmanthus fragrans var. thunbergii flower, including 58 phenylethanoids, 8 caffeoylquinic acids, 1 flavonoid vicenin-2, and 6 common organic chemicals in plant. Furthermore, 8 unknown alkaloids were characterized in this work. Among of these chemicals, 61 phenylethanoids were supposed to be detected for the first time. In conclusion, this work disclosed the potential hypoglycemic active constituents of Osmanthus fragrans var. thunbergii flower.

Non-coding RNA-mediated TGF-β1/Smads Signaling Pathway and Liver Fibrosis， and Intervention by Active Components of Chinese Medicinal： A Review / 中国实验方剂学杂志

Liver fibrosis is a wound healing response that occurs in the setting of chronic liver injury and is caused by imbalance in the synthesis and degradation of extracellular matrix （ECM）. If left untreated， it can progress to liver cirrhosis and hepatocellular carcinoma. The activation of hepatic stellate cell （HSC） is now well established as a central driver of liver fibrosis. The activated HSC will transform into myofibroblasts that produce ECM protein. Transforming growth factor-β1 （TGF-β1） can induce the activation of hepatic stellate cell （HSC）， and TGF-β1/Smads signaling pathway is one of the important pathways to promote liver fibrosis. Non-coding RNA （ncRNA） does not encode proteins during the transcription but plays an important regulatory role in the post-transcriptional process of genes. Accumulating evidence shows that the occurrence of liver fibrosis is closely related to the abnormal expression of ncRNA which participates in the activation of HSC by regulating TGF-β1 signal transduction and then affects the process of liver fibrosis. MiRNA-mediated TGF-β1/Smads signaling pathway can not only promote liver fibrosis but also play a role in anti-fibrosis. Long non-coding RNA （lncRNA） not only promotes the development of liver fibrosis by binding to target genes but also enhances TGF-β1 signal transduction by acting as competitive endogenous RNA. circular RNA （circRNA） acts as a ''sponge'' to regulate TGF-β1/Smads pathway， thereby inhibiting HSC activation and exerting the anti-liver fibrosis effect. Chinese medicinal plays an essential part in the prevention and treatment of liver fibrosis， and the active components can inhibit TGF-β1/Smads pathway by regulating the expression of miRNA， thus alleviating liver fibrosis. This article reviews the role and mechanism of miRNA-， lncRNA- and circRNA-mediated TGF-β1/Smads signaling pathway in liver fibrosis and summarizes the anti-liver fibrosis effect of active components of Chinese medicinals by regulating miRNA-mediated TGF-β1/Smads signaling pathway， which can serve as a reference for clinical treatment of liver fibrosis and the development of new drugs.