Piper nigrum L. is an evergreen climbing vine, which belongs to the genus Piperia in the Piperaceae family. Piper nigrum L., which known as the “king of spices”, is used as both food and medicine. The main active substances in Piper nigrum L. are alkaloids mainly composed of amides, and essential oil, as well as phenolic compounds. In this paper, the chemical compositions, especially amide alkaloids, and their biological activities of Piper nigrum L. were summarized. These studies showed that Piper nigrum L., as a medicinal and food plant, had a wide range of biological activities and was deserved further research and in-depth utilization.

Glutathione peroxidase （GSH-Px） is a key selenoenzyme that protects the body from oxidative damage. A series of small molecular organic selenium compounds have been designed and synthesized as functional mimics of GPx, among which isoselenazolones are the most widely studied. Taking ebselen as a representative, the catalytic mechanism of isoselenazolones in mimicing GSH-Px activity in vivo, the therapeutic effects of isoselenazolones in stroke, sensorineurium deafness and tinnitus, treatmentresistant depression （TRD） and coronavirus disease 2019 （COVID-19）, and research on their chemical synthesis methods were summarized and discussed in this paper.

The Department of Thoracic Surgery of Shanghai Chest Hospital has performed esophageal function testing for over 30 years, being the only department of its kind in China with this capability. The pressure testing and 24-hour pH/impedance monitoring of the esophagus is of great help to assist in the diagnosis and treatment of benign and malignant esophageal diseases related to it. Thanks to the esophageal function test, in addition to the routine various endoscopic anti-reflux procedures, our hospital has taken the lead in China in recent years to carry out a series of clinical and research work for benign esophageal diseases, such as the development of magnetic ring, double nedoscopic combination and new anti-reflux endoscopic techniques. In recent years, we have carried out high-resolution esophageal manometry and 24-hour pH/impedance monitoring for patients with interstitial pneumonia and pulmonary fibrosis suspected to be caused by gastroesophageal acid reflux. We can better assess the correlation between gastroesophageal reflux and pulmonary fibrosis, and to provide the different clinical treatments and even surgical interventions. The Bravo capsule is used more often in the United States, and it has obvious advantages over traditional approach for acid measurement. We strongly call for the collaboration between industry and academic institutions in this field, and the development of our own related products with independent intellectual property rights.

Most solid tumors suffer from inadequate blood perfusion and oxygenation, leading to a hypoxic microenvironment that accelerates tumor progression and adversely impacts prognosis. Thus, improving oxygenation in tumor tissues is crucial for enhancing the sensitivity and efficacy of tumor therapy. Hemoglobin-based oxygen carriers (HBOCs), as a type of oxygen-carrying nanoparticles, can not only carry and release oxygen but also reach the small blood vessels of obstructive microcirculation to deliver oxygen for anoxic tissues and organs, which are difficult for normal red blood cells to pass through. Studies have demonstrated that the application of HBOCs as a potential nanoscale efficient oxygen carrier in tumor therapy can enhance tissue oxygenation and hold great promise for applications in tumor therapy.This review summarizes the impact of hypoxia in tumors and highlights the progress and potential mechanisms of using HBOCs in tumor radiotherapy, chemotherapy, new kinetic therapy and immunotherapy.

【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) in chemoimmunotherapy for breast cancer in mice. 【Methods】 A 4T1 breast cancer in situ tumor model was established, and 15 mice were randomly divided into 3 groups: blank group: no intervention; Control group: doxorubicin + PD-1 inhibitor was given intraperitoneal injection of doxorubicin 5 mg·kg^-1 once a week and PD-1 inhibitor 12.5 mg·kg^-1 once a week; Experimental group: DOX+ a-PD-1+ PolyCHb, the usage of DOX and a-PD-1 was the same as above, PolyCHb: PolyCHb 600 mg·kg^-1 was injected into the tail vein, three times a week; The administration period was 4 weeks. During the administration, the tumor volume was recorded 3 times per week, the tumor growth curve of each group was drawn and the tumor inhibition rate was calculated. The mice were killed on the 29th day, and the tumor was removed and weighed to calculate the tumor inhibition rate. Immunofluorescence, HE staining, TUNEL method and immunohistochemistry was used to detect the expression of HIF-1α, observe the pathological changes of tumor tissue, detect the apoptosis of tumor cells, and detect the expression of tumor proliferation index Ki67. 【Results】 Compared with the blank group and the control group, the tumor volume in the experimental group decreased significantly (P<0.05) and the tumor inhibition rate (%) increased significantly (P<0.05). The content of HIF-1α in tumor tissue in experimental group decreased (P<0.05). In the experimental group, the growth area of tumor tissue decreased, accompanied by the increase of necrosis area; The positive rates (%) of apoptosis in tumor tissues of blank group, control group and experimental group were 18.79±0.62, 20.68±1.19 and 41.65±2.99 respectively (F=135.2, P<0.001). In addition, the results of tumor proliferation index Ki67 showed that there was a statistical difference between the control group and the experimental group (P<0.05). 【Conclusion】 PolyCHb increases the sensitivity of chemoimmunotherapy in breast cancer mouse model, and the mechanism may be related to the decrease of HIF-1α expression, the promotion of apoptosis and the inhibition of cell proliferation.

Aldehyde dehydrogenase 2 (ALDH2) is one of important factors against from the damage under oxidative stress in human body. A high proportion of East Asians carry ALDH2 inactive mutation gene. There are many diseases closely related to ALDH2, such as cardiovascular diseases, neurodegenerative diseases and liver diseases. Recent studies also have found that ALDH2 is associated with ferroptosis. Therefore, ALDH2 has becoming a potential target for the treatment of the above related diseases. Several types of small molecule activators with potential value of clinical application have been reported. The research progress on the structure and function of ALDH2 , the relationship with human diseases and its activators were summarized in this paper.

Objective:To investigate the causality between intestinal flora and hypertrophic scars (HS) of human.Methods:This study was a study based on two-sample Mendelian randomization (TSMR) analysis. The data on intestinal flora ( n=18 473) and HS ( n=208 248) of human were obtained from the genome-wide association study database. Genetically variable genes at five levels (phylum, class, order, family, and genus) of known intestinal flora, i.e., single nucleotide polymorphisms (SNPs), were extracted as instrumental variables for linkage disequilibrium (LD) analysis. Human genotype-phenotype association analysis was performed using PhenoScanner V2 database to exclude SNPs unrelated to HS in intestinal flora and analyze whether the selected SNPs were weak instrumental variables. The causal relationship between intestinal flora SNPs and HS was analyzed through four methods of TSMR analysis, namely inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode. Scatter plots of significant results from the four aforementioned analysis methods were plotted to analyze the correlation between intestinal flora SNPs and HS. Both IVW test and MR-Egger regression test were used to assess the heterogeneity of intestinal flora SNPs, MR-Egger regression test and MR-PRESSO outlier test were used to assess the horizontal multiplicity of intestinal flora SNPs, and leave-one-out sensitivity analysis was used to determine whether HS was caused by a single SNP in the intestinal flora. Reverse TSMR analyses were performed for HS SNPs and genus Intestinimonas or genus Ruminococcus2, respectively, to detect whether there was reverse causality between them. Results:A total of 196 known intestinal flora, belonging to 9 phyla, 16 classes, 20 orders, 32 families, and 119 genera, were obtained, and multiple SNPs were obtained from each flora as instrumental variables. LD analysis showed that the SNPs of the intestinal flora were consistent with the hypothesis that genetic variation was strongly associated with exposure factors, except for rs1000888, rs12566247, and rs994794. Human genotype-phenotype association analysis showed that none of the selected SNPs after LD analysis was excluded and there were no weak instrumental variables. IVW, MR-Egger regression, weighted median, and weighted mode of TSMR analysis showed that both genus Intestinimonas and genus Ruminococcus2 were causally associated with HS. Among them, forest plots of IVW and MR-Egger regression analyses also showed that 16 SNPs (the same SNPs number of this genus below) of genus Intestinimonas and 15 SNPs (the same SNPs number of this genus below) of genus Ruminococcus2 were protective factors for HS. Further, IVW analysis showed that genus Intestinimonas SNPs (with odds ratio of 0.62, 95% confidence interval of 0.41-0.93, P<0.05) and genus Ruminococcus2 SNPs (with odds ratio of 0.62, 95% confidence interval of 0.40-0.97, P<0.05) were negatively correlated with the risk of HS. Scatter plots showed that SNPs of genus Intestinimonas and genus Ruminococcus2 were protective factors of HS. Both IVW test and MR-Egger regression test showed that SNPs of genus Intestinimonas (with Q values of 5.73 and 5.76, respectively, P>0.05) and genus Ruminococcus2 (with Q values of 13.67 and 15.61, respectively, P>0.05) were not heterogeneous. MR-Egger regression test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity (with intercepts of 0.01 and 0.06, respectively, P>0.05); MR-PRESSO outlier test showed that the SNPs of genus Intestinimonas and genus Ruminococcus2 had no horizontal multiplicity ( P>0.05). Leave-one-out sensitivity analysis showed that no single intestinal flora SNP drove the occurrence of HS. Reverse TSMR analysis showed no reverse causality between HS SNPs and genus Intestinimonas or genus Ruminococcus2 (with odds ratios of 1.01 and 0.99, respectively, 95% confidence intervals of 0.97-1.06 and 0.96-1.04, respectively, P>0.05). Conclusions:There is a causal relationship between intestinal flora and HS of human, in which genus Intestinimonas and genus Ruminococcus2 have a certain effect on inhibiting HS.

Background and Purpose:The early prediction of local tumor progression-free survival(LTPFS)after radiofrequency ablation(RFA)for colorectal cancer(CRC)lung metastases has significant clinical importance.The application of radiomics in the prediction of tumor prognosis has been explored.This study aimed to construct a radiomics-based nomogram for predicting LTPFS after RFA in CRC patients with lung metastases.Methods:This study retrospectively analyzed 172 CRC patients with 401 lung metastases admitted to Department of Interventional Radiology,Fudan University Shanghai Cancer Center from August 2016 to January 2019.This study was reviewed by the medical ethics committee of Fudan University Shanghai Cancer Center(ethics number:2402291-24).After augmentation of pre-ablation and immediate post-ablation computed tomography(CT)images,the target metastases and ablation regions were segmented manually to extract the radiomic features.Maximum relevance and minimum redundancy algorithm(MRMRA)and least absolute shrinkage and selection operator(LASSO)regression models were applied for feature selection.The clinical model,the radiomics model,and the fusion model were constructed based on the selected radiomic features and clinical variables screened by the multivariate analysis.The Harrell concordance index(C-index)and area under receiver operating characteristic(ROC)curves(AUC)were calculated to evaluate the prediction performance.Finally,the corresponding nomogram of the best model was drawn.Results:Among all the lung metastases,102(25.4%)had final recurrence,and 299(74.6%)had complete response(CR).The median follow-up time was 21 months(95%CI:19.466-22.534),and the LTPFS rates at 1,2,and 3 years after RFA were 76.5%(95%CI:72.0-80.4),72.1%(95%CI:66.6-76.9)and 69.9%(95%CI:64.0-75.1).In both the training and test dataset,the fusion model based on the final 12 radiomic features through the LASSO regression and 4 clinical variables screened by multivariate analysis achieved the highest AUC values for LTPFS,with C-index values of 0.890(95%CI:0.854-0.927)and 0.843(95%CI:0.768-0.916),respectively.Conclusion:The fusion model based on radiomic features and clinical variables is feasible for predicting LTPFS after RFA of CRC patients with lung metastases,whose performance is superior to the single radiomic and clinical model.At the same time,the nomogram of the fusion model can intuitively predict the prognosis of CRC patients with lung metastases after RFA,thus assisting clinicians in developing individualized follow-up review plans for patients and adjusting treatment strategies flexibly.

Objective:This study compiled a comprehensive overview of the academic misconduct cases handled by the National Natural Science Foundation of China (NSFC) over the past decade, and took it as a representative to analyze the current situation of China′s academic research integrity to propose further enhancement suggestions.Methods:We collected data on academic misconduct cases notified by the NSFC between 2013 and 2022, and conducted a statistical analysis to gain insights into the time of occurrence, the way of discovery, the distribution of disciplines, the types of misconduct, and the handling measures of the NSFC.Results:Between 2013 to 2022, the Funding Committee notified 273 decisions regarding misconduct cases, indicating a general upward trend over time. Among the 158 cases with a labeled discovery pathway, the most common way was funding paper retraction by scientific journals, followed by reporting, and then review by the Funding Committee. The majority of individuals involved were from universities (44.81%) and hospitals affiliated with universities (45.45%). The top three most frequent types of misconduct were plagiarism, manipulation of reviews, and falsification. The Fund Committee's handling measures primarily involved in restrictions on applying for national funds within 2~7 years, notifications and criticisms, project withdrawals, and fund recoveries.Conclusions:Over the past ten years, the number of investigations of academic misconduct by the Fund Committee has been increasing, and the way of discovery has shifted from reporting and retraction by research journals to self-investigation by the Fund Committee. Biomedicine is a key field where misconduct occurs, and universities are the primary institutions where such cases are detected. Common causes of academic misconduct include plagiarism, manipulated peer review, and falsification. The foundation typically imposes punishments that restrict funding applications and issues public criticisms. To strengthen the academic integrity system, it is essential to establish and implement an early warning mechanism for academic integrity, reform the scientific research evaluation system, and establish an academic integrity management platform.

Objective To analyze the clinical efficacy of Yunnan Baiyao in middle aged and elderly lung cancer patients undergoing the uniportal video-assisted thoracoscopic.Methods A total of 90 patients with non-small cell lung cancer meeting the criterias were screened and divided into two groups according to random number table method,which respectively received conventional treatment(control group)and Yunnan Baiyao treatment(experimental group).The perioperative period related indexes,coagulation function related indexes,and the occurrence rate of complications were observed and compared between the two groups.Results The intraoperative bleeding volume and thoracic drainage volume for the first day of experimental group were significantly lower than control group(P＜0.05).However,there were no significant difference in the coagulation function related indexes between two groups before and after surgery(P＞0.05).Additionally,there were also no significant difference in the occurrence rate of complication between two groups(P＞0.05).Conclusion Yunnan Baiyao can reduce intraoperative bleeding volume and chest tube drainage volume for the first day,promots the recovery of patients,and has a good clinical application value.