ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

ObjectiveTo investigate the mechanism by which modified Shengjiangsan （MSJS） improves diabetic kidney disease （DKD） by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar， high-fat diet combined with intraperitoneal injection of streptozotocin （STZ）. After successful modeling， the rats were randomly divided into six groups： a normal control group， a model group， low-， medium-， and high-dose MSJS groups （7.7， 15.4， 30.8 g·kg^-1， respectively）， and an irbesartan group （0.384 g·kg^-1）. Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose， body weight， and kidney weight were recorded. Serum creatinine （SCr） and blood urea nitrogen （BUN） levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay （ELISA） was used to determine urinary microalbumin （mALB）， and serum levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6）. Histopathological changes in renal tissues were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy （TEM）. The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta （LC3B） and cytochrome c oxidase subunit Ⅳ （COX Ⅳ）. ResultsCompared with the normal control group， the model group exhibited significant increases in renal index， blood glucose， and 24-hour urinary microalbumin （24 h mALB） （P<0.05， P<0.01）. The levels of serum SCr and BUN were significantly elevated （P<0.01）， and the serum levels of TNF-α， IL-1β， and IL-6 were markedly upregulated （P<0.01）. Histopathological examination revealed glomerular hypertrophy， mesangial expansion and increased deposition， podocyte foot process flattening and fusion， a decreased number of autophagosomes accompanied by mitochondrial swelling， vacuolar degeneration of renal tubular epithelial cells， and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B， PTEN-induced putative kinase 1 （PINK1）， and E3 ubiquitin-protein ligase （Parkin） were significantly decreased （P<0.05， P<0.01）， while expression of the selective autophagy adaptor protein p62 was significantly increased （P<0.01）. Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group， the MSJS treatment groups and the irbesartan group showed significant reductions in renal index， blood glucose， and 24 h mALB （P<0.05， P<0.01）. The serum SCr and BUN levels decreased significantly （P<0.05） and TNF-α， IL-1β， and IL-6 levels were significantly downregulated （P<0.05， P<0.01）. Histopathological damage was alleviated， including reduced glomerular hypertrophy， decreased mesangial deposition， and attenuated podocyte foot process fusion. The number of autophagosomes increased， and mitochondrial swelling was improved. The expression levels of LC3B， PINK1， and Parkin in renal tissues were significantly upregulated， whereas p62 expression was significantly downregulated （P<0.05， P<0.01） in MSJS groups. Immunofluorescence signal intensity was enhanced， and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

Objective To systematically evaluate the efficacy and safety of proximal gastrectomy (PG) versus total gastrectomy (TG) for the treatment of Siewert type Ⅱ/Ⅲ adenocarcinoma of the esophagogastric junction (AEG). Methods PubMed, The Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, and VIP databases were searched for literature comparing the efficacy and safety of PG and TG for the treatment of Siewert type Ⅱ/Ⅲ AEG. The search period was from database inception to March 2023. Meta-analysis was performed using Review Manager 5.4 software. Results A total of 23 articles were included, including 16 retrospective cohort studies, 5 prospective cohort studies, and 2 randomized controlled trials. The total sample size was 2 826 patients, with 1 389 patients undergoing PG and 1 437 patients undergoing TG. Meta-analysis results showed that compared with TG, PG had less intraoperative blood loss [MD=−19.85, 95%CI (−37.20, −2.51), P=0.02] and shorter postoperative hospital stay [MD=−1.23, 95%CI (−2.38, −0.08), P=0.04]. TG had a greater number of lymph nodes dissected [MD=−6.20, 95%CI (−7.68, −4.71), P<0.001] and a lower incidence of reflux esophagitis [MD=3.02, 95%CI (1.24, 7.34), P=0.01]. There were no statistically significant differences between the two surgical approaches in terms of operative time, postoperative survival rate (1-year, 3-year, 5-year), and postoperative overall complications (P>0.05). Conclusion PG has advantages in terms of intraoperative blood loss and postoperative hospital stay, while TG has advantages in terms of the number of lymph nodes dissected and the incidence of reflux esophagitis. There is no significant difference in long-term survival between the two surgical approaches.

Objective To systematically evaluate the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer. Methods PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang, VIP, CNKI and Chinese Biomedical Literature database were searched for literature on the short-term efficacy and safety of McKeown and Sweet methods in the treatment of esophageal cancer published from the establishment to May 2023. Newcastle-Ottawa Scale was used to evaluate the quality of researches, and meta-analysis was performed using RevMan5.4. Results A total of 9 articles were included, involving 3687 patients including 1019 in the McKeown group and 2668 in the Sweet group. NOS score was 8-9 points. There were no statistical differences in the age, sex or American Joint Committee on Cancer stage between the two groups (P>0.05). Patients in the McKeown group had longer operative time and hospital stay, more intraoperative blood loss, and higher Eastern Cooperative Oncology Group scores than those in the Sweet group (P<0.05). However, the McKeown operation could remove more lymph nodes (P=0.001). In terms of safety, the incidences of pulmonary complications [OR=2.20, 95%CI (1.40, 3.46), P=0.001] and postoperative anastomotic leakage [OR=2.06, 95%CI (1.45, 2.92), P=0.001] were higher in the McKeown group than those in the Sweet group. In addition, there were no statistical differences between the two groups in the Karnofsky score, cardiac complications, vocal cord injury or paralysis, chylous leakage, or gastric emptying (P>0.05). Conclusion Compared with McKeown, Sweet method has advantages in operation time, intraoperative blood loss and hospital stay, and has lower incidence of postoperative pulmonary complications and anastomotic leakage. However, McKeown has more lymph node dissection.

Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

L-phosphinothricin (L-PPT) is an efficient broad-spectrum herbicide. To realize the multi-enzyme catalytic preparation of L-PPT, we constructed an engineered strain Escherichia coli YM-1 for efficient expression of D-amino acid transaminase, which could catalyze the generation of the intermediate 2-oxo-4-[(hydroxymethylphosphonyl)] butyric acid (PPO) from D-phosphinothricin (D-PPT). In addition, E. coli pLS was constructed to co-express glutamate dehydrogenase and glucose dehydrogenase, which not only catalyzed the generation of L-PPT from PPO but also regenerated the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH). A fed-batch fermentation process was then established for E. coli YM-1 and pLS, and the apparent activities of D-amino acid transaminase and glutamate dehydrogenase were increased by 22.68% and 100.82%, respectively, compared with those in shake flasks. The process parameters were optimized for the catalytic preparation of L-PPT by whole-cell cascade of E. coli YM-1 and pLS with D, L-PPT as the substrate. After reaction for 8 h, 91.36% conversion of D-PPT was achieved, and the enantiomeric excess of L-PPT reached 90.22%. The findings underpin the industrial production of L-PPT.
Escherichia coli/enzymology* ; Aminobutyrates/metabolism* ; Glutamate Dehydrogenase/biosynthesis* ; Glucose 1-Dehydrogenase/biosynthesis* ; Herbicides/metabolism* ; Multienzyme Complexes/metabolism* ; Transaminases/metabolism* ; Phosphinic Acids/metabolism*

AIM:To investigate the effects of adipose-derived stem cells(ADSCs)with overexpression or si-lencing of long noncoding RNA(lncRNA)SNHG8 on the viability,migration,angiogenesis,and the expression of vasoac-tive factors in human umbilical vein endothelial cells(HUVECs).METHODS:Identification of ADSCs derived from morbidly obese patients(O-ADSCs)was conducted using flow cytometry and induction of lipogenesis and osteogenesis.The expression of lncRNA SNHG8 in healthy human ADSCs(H-ADSCs)and O-ADSCs was detected by RT-qPCR.Tran-swell method was used to establish the indirect co-culture system of ADSCs and HUVECs for 48 h,and the cells were di-vided into O-ADSCs+HUVECs group,H-ADSCs+HUVECs group,and HUVECs alone group.The mRNA and protein ex-pression levels of angiotensin Ⅱ(Ang Ⅱ),endothelin-1(ET-1)and endothelial nitric oxide synthase(eNOS)in HUVECs were detected by RT-qPCR and Western blot.The lncRNA SNHG8 overexpression and silencing lentiviruses were con-structed and used to infect O-ADSCs.The indirect co-cultured ADSCs and HUVECs were divided into O-ADSCs-OE-SNHG8+ HUVECs group,O-ADSCs-OE-NC+HUVECs group,O-ADSCs-sh-SNHG8+HUVECs group,and O-ADSCs-sh-NC+HUVECs group.After co-culture for 48 h,the viability,migration and tubule formation of HUVECs were detected by CCK-8,scratch and angiogenesis assays,respectively.The mRNA and protein expression levels of Ang Ⅱ,ET-1 and eNOS in HU-VECs were detected by RT-qPCR and Western blot,respectively.The nitrate reductase method was used to detect the con-tent of NO in HUVECs.RESULTS:(1)The cultured cells were identified as ADSCs.(2)Compared with H-ADSCs,ln-cRNA SNHG8 expression was significantly up-regulated in O-ADSCs(P<0.01).(3)Compared with H-ADSCs+HUVECs group and HUVECs group,the mRNA and protein expression levels of Ang Ⅱ and ET-1 in HUVECs in O-ADSCs+HU-VECs group were up-regulated(P<0.01).(4)Overexpression of lncRNA SNHG8 in O-ADSCs enhanced the viability,mi-gration and tube formation ability of HUVECs,up-regulated the mRNA and protein expression levels of Ang Ⅱ and ET-1,down-regulated the mRNA and protein expression levels of eNOS,and decreased the content of NO in HUVECs(P<0.05).However,silencing of lncRNA SNHG8 in O-ADSCs exerted opposite results(P<0.05).CONCLUSION:(1)The O-ADSCs can promote endothelial cell viability,migration and tubule formation through paracrine effects.(2)The O-ADSCs with overexpression of lncRNA SNHG8 promote the imbalance of diastolic and contractile factors secreted by endo-thelial cells,and induce the dysfunction of vascular endothelial cells.

AIM: To explore retinal microvascular changes in migraine patients using meta-analysis.METHODS: The National Library of Medicine PubMed, Embase, and Cochrane Library were searched to find relevant studies, and the search period was from the creation of database to June 2023. Two investigators independently screened the literatures, extracted data, and evaluated the quality of included studies using the NOS scale. STATA15.0 was used for Meta-analysis and publication bias evaluation, sensitivity analysis was performed for results with large heterogeneity, and the funnel plot and Egger were used to assess the publication bias of the literature.RESULTS:A total of 12 studies, including 217 patients(252 eyes)with migraine with aura(MA), 283 patients(388 eyes)with migraine without aura(MO), and 374 healthy individuals(479 eyes), were included in this Meta-analysis. Several optical coherence tomography angiography(OCTA)indicators, including foveal avascular zone(FAZ)macular or optic disc perfusion density were compared and analyzed. The Meta-analysis results showed that compared with healthy controls, patients with MA had a significant increase in FAZ area and perimeter, a significant decrease in perfusion density of the macular deep capillary plexus(mDCP)except for the fovea, and a significant decrease in perfusion density of the radial peripapillary capillaries(RPC)around the optic disc; the FAZ parameters were significantly increased in MO, while the differences in perfusion density of the macular superficial capillary plexus(mSCP), mDCP and RPC were not statistically significant, except for the perfusion density in the parafovea mDCP.CONCLUSIONS: Both MA and MO patients had an enlarged FAZ area, patients with MA had a significant decrease in mDCP perfusion density, and migraine patients had some degree of retinal ischemia.

AIM:To systematically evaluate the changes in retinal and choroidal thickness in patients with internal carotid artery stenosis by using optical coherence tomography(OCT)through Meta-analysis.METHODS: Literatures on the measurement of retinal and choroidal structure in patients with internal carotid artery stenosis by using OCT from CNKI, VIP, WF, PubMed, the Cochrane Library, SinoMed, and Embase databases were searched for relevant studies. The retrieval time was from the establishment of the databases to January 2024. In addition, quality of the included literatures was assessed by the Newtle-Ottawa scale(NOS), and RevMan 5.4.1 and Stata 16.0 were used for statistical analysis.RESULTS: A total of 17 articles(including 18 studies)were included, and the Meta-analysis results showed that, patients with internal carotid artery stenosis had significantly thinner peripapillary retinal nerve fiber layer(pRNFL), ganglion cell complex(GCC), center macular thickness(CMT), and subfoveal choroidal thickness(SFCT)than the healthy control group(age matched normal population). The pRNFL and SFCT of the ipsilateral eye in patients with internal carotid artery stenosis become thinner compared with the contralateral eye.CONCLUSION:To a certain extent, the morphological structure of the retina and choroid can be altered by stenosis of the internal carotid artery. OCT can non-invasively detect the microstructural changes of the retina and choroid in patients with internal carotid artery stenosis, and can be used for the evaluation of internal carotid artery stenosis.

Objective To explore the anti-depression mechanism of Kai-Xin-San(KXS)via regulation of neurogenesis in hippocampus of depression-like mice.Methods The extracts of KXS were prepared and the anti-depression effects of KXS were evaluated by behavioral tests on chronic unpredictable mild stress(CUMS)induced depression-like mice.Evaluating depression-like behavior in CUMS mice through sucrose preference test,forced swimming test,tail suspension test,and other methods.Neurogenesis in hippocampus were determined by immunofluorescence assay.In addition,effects of KXS on regulating nestin expression and Wnt/b-catenin signaling pathway were explored by western blotting analysis.Amounts of cortisol,corticotropin-releasing factor(CRF),adrenocorticotropic hormone(ACTH),brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)were determined by ELISA tests.Mouse primary neural stem cells(NSC)was used to evaluate the effect of KXS on promoting its proliferation by immunofluorescence assay.In addition,effects of KXS on regulating nestin and Wnt/β-catenin signaling pathway were also explored by Western blotting analysis.Results KXS significantly ameliorated the depression-like behaviors in presence of increased sucrose preference rate and decreased immobile time of tail suspension and forced swimming.KXS significantly promoted the neurogenesis in the hippocampus and expressions of nestin,reduced the expressions of cortisol,CRF,ACTH,increased the expressions of BDNF,NGF,and regulated Wnt/β-catenin signaling pathway.KXS also promoted the proliferation of NSCs and expressions of nestin,enhanced the translocation of b-catenin into nucleus,and regulated the expressions of proteins of Wnt/β-catenin signaling pathway.Conclusion KXS promoted neurogenesis in hippocampus and regulated Wnt/β-catenin pathway,which might contribute to its antidepressant effect.