BACKGROUND:During tissue repair and regeneration,macrophages exhibit multiple activities such as promoting inflammation,anti-inflammation,fibrosis,and wound healing at various stages of tissue damage.The heterogeneity and balanced polarization of macrophages are decisive in organ repair. OBJECTIVE:To explore the research hotspots and development trends in the field of macrophage polarization in tissue repair through visualization analysis methods,as well as the research level of global scientific and clinical workers in this field. METHODS:Using bibliometric analysis methods,this study employed Citespace literature visualization analysis software and VOSviewer tools,retrieving related literature from 2013 to 2023 in the Web of Science Core Collection's Science Citation Index Expanded(SCI-Expanded)and Social Sciences Citation Index Expanded(SSCI-Expanded)databases.The analysis results were presented in a dynamic map format,revealing the main trends and focuses of the research. RESULTS AND CONCLUSION:The number of publications in this field had dramatically increased from 2013 to 2023,with a significant rise starting in 2017.Chinese researchers had the highest number of publications,with 642 papers,while American researchers began focusing on this field early on.Professor Elisseeff Hennifer H had made a substantial contribution to the research in this area.Shanghai Jiao Tong University had produced the most publications.In recent years,keywords such as"hyaluronic acid"and"regulation"had been prevalent.Macrophage polarization research in tissue repair primarily concentrates on its multifunctional regulatory mechanisms,interactions with other cell types,and its behavior under specific pathological conditions.The main research areas include the role of macrophages in wound healing,cardiovascular diseases,chronic inflammation,tumor microenvironments,and regenerative medicine.A deeper understanding of the multifunctionality and polarization mechanisms of macrophages can lead to the development of new therapeutic strategies to enhance tissue repair and regeneration,thereby improving patient treatment outcomes.

Objective To generate and characterize natural killer cell (NK cell)-conditional Cd226 gene knockout mice using Cre-loxP technology, and to explore the role of CD226 on NK cells in alleviating intestinal inflammation in a murine model of ulcerative colitis (UC). Methods NK cell-conditional Cd226 gene knockout mice were generated by crossing loxP-flanked Cd226 mice with Ncr1-Cre mice via the Cre-loxP system. Polymerase chain reaction (PCR) and agarose gel electrophoresis were used for genotyping. A UC model was established by dextran sulfate sodium (DSS) induction. Flow cytometry was performed to analyze CD226 expression levels on NK cells and the infiltration of related immune cells in colon tissues. Hematoxylin-eosin (HE) staining was performed to assess the degree of colonic inflammation. Results DNA gel electrophoresis and flow cytometry confirmed the successful generation of NK cell-specific Cd226 knockout mice. After conditional knockout of Cd226 in NK cells, inflammation in the UC mouse model was alleviated. Flow cytometry results showed a reduced proportion of NK cells in peripheral blood and the colon lamina propria, while HE staining demonstrated attenuated inflammatory responses. Conclusion Specific knockout of Cd226 in NK cells mitigates intestinal inflammation in UC mice by reducing NK cell numbers and inhibiting their pro-inflammatory functions.
Animals ; Colitis, Ulcerative/pathology* ; Killer Cells, Natural/metabolism* ; Mice, Knockout ; T Lineage-Specific Activation Antigen 1 ; Antigens, Differentiation, T-Lymphocyte/genetics* ; Mice ; Disease Models, Animal ; Mice, Inbred C57BL ; Male

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0.Methods:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results:The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Objective:To investigate the effect of sevoflurane and propofol on cognitive function, respiratory and circulatory function, and stress response in patients undergoing laparoscopic radical gastrectomy.Methods:A prospective randomized controlled study was conducted. A total of 116 patients who underwent laparoscopic radical gastric cancer surgery in Liangshan Yi Autonomous Prefecture Hospital of Integrated Chinese and Western Medicine from January 2021 to January 2022 were selected, and all patients were divided into the propofol group and the sevoflurane group according to the random number table method, with 58 cases in each group. Propofol anesthesia was used in the propofol group and sevoflurane anesthesia was used in the sevoflurane group. The anesthesia-related indexes and respiratory and circulatory function indexes, oxidative stress parameters and cognitive function indexes neuron-specific enolase (NSE) levels, Mini-Mental State Examination (MMSE) scale score, and complications at different time points were compared between the 2 groups.Results:There were no statistically significant differences in the baseline data between the 2 groups (all P > 0.05). The differences in intraoperative bleeding, pneumoperitoneum time and anesthesia onset time between the 2 groups were not statistically significant (all P > 0.05); eye opening time [(13.2±2.6) min vs. (17.6±3.7) min] and respiratory recovery time [(12.6±2.2) min vs. (16.5±2.3) min] of patients in the sevoflurane group were shorter than those in the propofol group, and the differences were statistically significant ( t values were 7.41 and 9.31, respectively, both P < 0.001). Repeated measurement analysis of variance showed that the temporal, intergroup and temporal-intergroup interaction differences in heart rate, mean arterial pressure and oxygen saturation before induction of anesthesia, immediately after induction of anesthesia, and at the time of anesthesia duration of 10 min, anesthesia duration of 20 min, and anesthesia duration of 30 min between the propofol group and the sevoflurane group were not statistically significant (all P>0.05). The temporal, intergroup and temporal-intergroup interaction differences in the oxidative stress indexes of blood glucose, adrenaline, adrenocorticotropin, and cortisol between the 2 groups were statistically significant (all P < 0.001). The levels of blood glucose, epinephrine, adrenocorticotropin and cortisol in the sevoflurane group were lower than those in the propofol group immediately after induction of anesthesia, and at the time of anesthesia duration of 10 min, anesthesia duration of 20 min, and anesthesia duration of 30 min. The level of NSE before anesthesia in the propofol group and the sevoflurane group was (6.6±0.8) ng/ml and (6.5±0.7) ng/ml, respectively, and there was no statistically significant difference ( P > 0.05). The level of NSE in the sevoflurane group was higher than that in the propofol group immediately after surgery [(8.9±0.8) ng/ml vs. (8.2±0.9) ng/ml], 6 h after surgery [(10.2±1.2) ng/ml vs. (9.5±1.0) ng/ml], and 24 h after surgery [(9.3±1.1) ng/ml vs. (8.2±0.9) ng/ml] and 48 h after surgery [(8.7±0.9) ng/ml vs. (8.1±0.9) ng/ml]; and there were temporal, intergroup and temporal-intergroup interaction differences in NSE level of the 2 groups (all P < 0.001). The MMSE score in the sevoflurane group was lower than that in the propofol group immediately after surgery, 6 h after surgery, 24 h after surgery, 48 h after surgery, the temporal, intergroup and temporal-intergroup interaction differences in MMSE scale score of the 2 groups were statistically significant (all P < 0.001). The incidence of postoperative complications in the propofol group and the sevoflurane group was 24.1% (14/58) and 25.9% (15/58), respectively, and the difference was statistically significant ( χ2 = 2.12, P = 0.833). Conclusions:Sevoflurane and propofol anesthesia have no significant effect on the respiratory and circulatory functions of patients undergoing laparoscopic radical surgery for gastric cancer, whereas propofol has a smaller effect on cognitive functions, and sevoflurane inhibits oxidative stress better. Both of them are worthy of clinical application.

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P＜0.001,P＜0.001,P＜0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P＜0.001,P＜0.001)and invasion(all P＜0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P＜0.001,P＜0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P＜0.001,P＜0.001)and reactive oxygen species accumula-tion(all P＜0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P＜0.001,P＜0.001),heme oxygenase 1(P=0.015,P＜0.001,P＜0.001),and Bc12(P=0.039,P＜0.001,P＜0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P＜0.001)and up-regulated Bax expression(both P＜0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P＜0.001),apoptosis(P＜0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.

Malignant tumors are a major disease threatening human health with disability and mortality rates increasing yearly.Protein tyrosine phosphatase 2(SHP2)of Src homology 2,an important member of the protein tyrosine phosphatase family,has a wide range of functions,and its expression is elevated in a wide range of solid tumors.SHP2 plays an important regulatory role in invasion,metastasis,proliferation,apoptosis,and drug resistance.A large number of studies have shown that SHP2 plays a very important role in the genesis and development of many solid tumors,but no systematic studies have reported on the role of SHP2 in digestive system tumors.Here,we reviewed the biological functions and clinical significance of SHP2 in seven tumor types of the digestive system,explored its roles and mechanisms in cancer development stages,and summarized the development of SHP2 inhibitors to further search for potential targets for effective early diagnosis and gene therapy,which is of great significance to improvement the cancer patient survival rate.

AIM:To evaluate the therapeutic effect of Shen-Xiankang formula on renal interstitial fibrosis in-duced by unilateral ureteral obstruction(UUO)in mice and to elucidate its underlying mechanisms.METHODS:Thirty-two C57BL/6 mice were randomly divided into sham group,UUO model group,and Shen-Xiankang formula intervention groups receiving either a low dose(150 mg·kg-1·d-1)or a high dose(450 mg·kg-1·d-1),with 8 mice in each group.All mice except those in sham group underwent UUO to establish chronic kidney disease(CKD)model.After modeling,cor-responding doses of Shen-Xiankang or an equivalent volume of saline were administered daily for 7 d.Upon completion of treatment,renal tissues were collected for hematoxylin-eosin(HE)and Masson staining to assess tissue damage and fibro-sis.Immunohistochemistry and Western blot analyses were used to detect the markers of fibrosis,oxidative stress,and fer-roptosis.The effect of Shen-Xiankang formula on the interaction between activating transcription factor 3(ATF3)and Smad3 was assessed using co-immunoprecipitation(Co-IP).RESULTS:The untreated UUO model group exhibited nota-ble pathological changes such as expanded renal tubules and collagen deposition.Shen-Xiankang treatment significantly alleviated these changes(P<0.05).It markedly reduced Smad3 phosphorylation,ATF3,4-hydroxynonenal(4-HNE),and NADPH oxidase 4(NOX4)aberrant expression,while increasing glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)expression.Co-IP results indicated a significant modulation of the ATF3-Smad3 interac-tion by Shen-Xiankang.CONCLUSION:Shen-Xiankang formula effectively mitigates UUO-induced renal interstitial fi-brosis in mice.The mechanism may involve modulating the ATF3/Smad3 interaction,which in turn attenuates oxidative stress and ferroptosis,consequently leading to the amelioration of renal fibrosis.These findings provide important insights for further research and clinical application of Shen-Xiankang formula.