Objective To evaluate the efficacy of combining the replenishing qi and nourishing yin empirical formula with anti-vascular endothelial growth factor (VEGF) in diabetic macular edema (DME). Methods A retrospective analysis was conducted on 59 patients diagnosed with DME at Tongji Hospital of Tongji University or Shanghai Nanxiang Hospital, Jiading District from June 2019 to December 2022. Among them, 29 cases received intravitreal injection of ranibizumab (anti-VEGF group), while 30 cases received both intravitreal injection of ranibizumab and oral administration of the replenishing qi and nourishing yin empirical formula (combined treatment group). The best corrected visual acuity (BCVA), central macular thickness (CMT), and the traditional Chinese medicine (TCM) syndrome score were compared between the two groups before treatment and at 4, 8, 12, 16, 20, and 24 weeks after treatment. Results Compared with before treatment, BCVA significantly improved (P＜0.05) and CMT significantly decreased (P＜0.05) at different time points after treatment in both groups. At 16, 20, and 24 weeks after treatment, BCVA in the combined treatment group was superior to that in the anti-VEGF group (P＜0.01). At 12, 16, 20, and 24 weeks after treatment, CMT in the combined treatment group was lower than that in the anti-VEGF group (P＜0.01). Starting from week 8 after treatment, the TCM syndrome scores in the combined treatment group were lower than those in the anti-VEGF group (P＜0.01). Conclusions The replenishing qi and nourishing yin empirical formula could improve the efficacy of anti-VEGF therapy in DME patients, indicating that integrating traditional Chinese and Western medicine has certain clinical application value in treating DME.

Objective To investigate the regulatory effect of suppressor of cytokine signaling 1 (SOCS1) on the proliferation and apoptosis of myelodysplastic syndrome (MDS) cells SKM-1 and its potential mechanisms. Methods SOCS1 was overexpressed in SKM-1 cells by transfection with exogenous SOCS1-overexpressing plasmid. Cell viability, cell cycle and apoptosis were analyzed with CCK-8 and flow cytometry assays, respectively. Western blot was used to evaluate the expression of proteins related to the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway. Additionally, a NOD/SCID mouse model of MDS was established to record mouse body weight and survival time, assessing the impact of the SOCS1 gene on the growth of SKM-1 cells in vivo. Results Transfection of the SOCS1-overexpressing plasmid significantly increased the mRNA and protein expression levels of SOCS1 in the MDS cell line SKM-1. Overexpression of SOCS1 remarkably reduced cell viability, inhibited cell proliferation, and promoted apoptosis of SKM-1 cells, which also decreased the expression of phosphorylated-JAK2 (p-JAK2), phosphorylated-STAT3 (p-STAT3), and p-STAT5 proteins. Furthermore, in vivo experiment results showed that the body weight and survival time of mice in the SOCS1 overexpression group were significantly better than those in the MDS model group, and the number of CD45⁺ SKM-1 cells in the peripheral blood was significantly lower than that in the MDS model group, indicating that SOCS1 overexpression could inhibit the activity of SKM-1 cells in mice. Western blot results verified the protein expression level of SOCS1 in the bone marrow of mice in the SOCS1 overexpression group was significantly higher than that in the MDS model group, while the protein expression levels of p-JAK2, p-STAT3, and p-STAT5 were significantly lower than those in the MDS model group. Conclusion SOCS1 inhibits the proliferation of MDS cell line SKM-1 and promotes its apoptosis by negatively regulating the JAK2/STAT signaling pathway, making it a potential therapeutic target for myelodysplastic syndromes.
Animals ; Humans ; Mice ; Apoptosis ; Body Weight ; Bone Marrow/metabolism* ; Janus Kinase 2/metabolism* ; Mice, Inbred NOD ; Mice, SCID ; Myelodysplastic Syndromes/metabolism* ; Phosphorylation ; STAT3 Transcription Factor/metabolism* ; STAT5 Transcription Factor/metabolism* ; Suppressor of Cytokine Signaling 1 Protein/metabolism* ; Cell Proliferation

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Objective To discuss the clinical value of flat head CT of two-way digital flat angiography system(DSA)in predicting symptomatic intracranial hemorrhage in patients with acute anterior circulation-large vessel occlusion cerebral infarction occurring within 24 hours after operation.Methods A total of 264 patients with acute anterior circulation-large vessel occlusion cerebral infarction,who were admitted to the Shanghai Changhai hospital to receive treatment from January 2020 to January 2023,were selected for this study.Mechanical thrombectomy was carried out in all the patients,and DSA flat head CT examination was performed 24 hours after operation.According to whether the postoperative DSA plate head CT scan showed high-density shadow or not,the patients were divided into observation group(showing high-density shadow,n=176)and control group(showing no high-density shadow,n=88).The clinical data,therapeutic regimen,and intracranial hemorrhage within 24 hours after operation were compared between the two groups.Taking head CT results as the standard,the clinical value of DSA flat head CT scan performed immediately after operation in predicting symptomatic intracranial hemorrhage occurring within 24 hours after operation was evaluated.Results Among the 264 patients with acute anterior circulation-large vessel occlusion cerebral infarction,118 patients developed intracranial hemorrhage within 24 hours after operation,including 24 patients(20.34％)having symptomatic intracranial hemorrhage.No statistically significant differences in clinical data and therapeutic regimen existed between the two groups(P＞0.05).The sensitivity,specificity and accuracy of DSA flat head CT scan performed immediately after operation in predicting intracranial hemorrhage occurring within 24 hours after operation in the observation group were 97.46％,58.22％and 75.76％respectively.The detection rate of symptomatic intracranial hemorrhage occurring within 24 hours after operation in the observation group was higher than that in the control group,the difference between the two groups were statistically significant(P＜0.05).The sensitivity,specificity and accuracy of DSA flat head CT scan performed immediately after operation in predicting symptomatic intracranial hemorrhage occurring within 24 hours after operation were 87.50％,57.48％and 40.15％respectively.The sensitivity,specificity and accuracy of DSA flat head CT scan in predicting the transformation of cerebral hemorrhage were 95.67％,63.12％and 80.23％respectively.Conclusion In patients with acute anterior circulation-large vessel occlusion cerebral infarction,who develop intracranial hemorrhage within 24 hours after mechanical thrombectomy,DSA flat head CT scan performed immediately after operation often shows high-density shadow,which is very helpful in predicting the risk of postoperative intracranial hemorrhage,the clinicians should make an early diagnosis and response to a possible symptomatic intracranial hemorrhage.

Acute myocardial infarction is caused by continuous ischemia and hypoxia of myocardial cells,leading to myocardial cell necrosis.Reperfusion therapy is the standard strategy for reducing infarct size and improving the prognosis of myocardial infarction.However,myocardial injury caused by reperfusion therapy is accompanied by various pathophys-iological processes,such as oxidative stress,inflammatory response,myocardial fibrosis,extracellular matrix remodeling,etc.Transcription factor EB(TFEB)is a central regulatory factor in the autophagy-lysosome signaling pathway,involved in signaling pathways such as stress response,myocardial energy metabolism,autophagy,and lysosomal biogenesis.It is closely related to the repair of myocardial injury after myocardial infarction.This review aims to elucidate the mechanism of TFEB in myocardial ischemic injury.

Objective:To observe the effects of 12.5% carbohydrate (CHO) solution and medium chain triglycerides (MCT) solutions at various concentrations on gastric emptying, in order to determine the optimal MCT-CHO combination for enhanced recovery after surgery.Methods:This study was a prospective study. Ten healthy volunteers were selected to ingest 400 ml of the following 5 solutions every day: water, 12.5% CHO, 1% MCT, 2% MCT and 4% MCT. According to the above results, the optimal concentration of MCT solution was 2% MCT, showing comparable gastric emptying rate compared with 12.5% CHO solution. On this basis, combinations of MCT and CHO solutions were determined to be 30 energy % (EN%) MCT+70 EN% CHO and 20 EN% MCT+80 EN% CHO according to the energy distribution ratio. Then the volunteers were given 400 ml of the following 4 solutions every day: 12.5% CHO, 2% MCT, 30 EN% MCT+70 EN% CHO (equivalent to 2% MCT+8% CHO), and 20 EN% MCT+80 EN% CHO (equivalent to 4.4% MCT+10% CHO). Gastric emptying during fasting (T m) and immediately (T 1), 30 min (T 2), 60 min (T 3), 90 min (T 4) and 120 min after ingestion (T 5) were observed by antral ultrasonography. The degree of thirst, hunger, and anxiety was assessed by Visual Analogue Scale, and the taste was rated. Results:The gastric emptying rate in descending order was 20%EN MCT+80%EN CHO group>30%EN MCT+70%EN CHO group≈2％MCT group≈12.5%CHO group. There was no significant difference in gastric emptying rate between 30 EN% MCT+70 EN% CHO group and 12.5% CHO group ( P>0.05). The scores of thirst, hunger and anxiety in 30 EN% MCT+70 EN% CHO group at T 1 to T 5 were significantly lower than those at T m ( P<0.05). 30 EN% MCT+70 EN% CHO group showed the highest taste score. Conclusion:30 EN% MCT+70 EN% CHO solution has similar gastric emptying rate compared with 12.5% CHO solution. It can relieve thirst, hunger, anxiety and other subjective feelings caused by fasting, with tastes better than 12.5% CHO solution.

ObjectiveTo investigate the serotype distribution and antimicrobial resistance characteristics of foodborne Salmonella in infectious diarrhea cases in Minhang District, Shanghai, and to provide evidence for clinical diagnosis, treatment, prevention, and control of salmonellosis. MethodsFecal or anal swab samples were collected from foodborne diarrhea cases at sentinel hospitals between 2019 and 2023 in Minhang District of Shanghai. Salmonella was isolated, biochemically identified, and serotyped. Antimicrobial susceptibility testing was performed via the microbroth dilution method. ResultsA total of 4 294 samples were collected, from which 224 Salmonella strains were isolated, with an isolation rate of 5.22%. There was no gender difference in the positive rate of Salmonella. The positive rate showed seasonal fluctuations (χ²=160.475, P<0.001), with a higher positive rate in summer and autumn than in spring and autumn. Among different occupational groups, the positive rate was the highest among retired people (7.30%) (χ²=20.023, P=0.001). Among different age groups, the positive rate was the highest among those aged 80 years and above (7.33%) (χ²=13.491, P=0.009). A total of 28 serotypes were identified, with Salmonella Enteritidis being the most predominant, followed by Salmonella Typhimurium. Among them, 154 strains were multi-drug resistant to three or more types of antibiotics (68.75%). The most common drug resistance patterns among multi-drug resistant strains were ampicillin (AMP)-ampicillin/sulbactam (AMS)-sulfamethoxazole/trimethoprim (SXT)-chloramphenicol (CHL)-tetracycline (TET)-streptomycin (STR), AMP-TET-STR and AMP-AMS-TET-STR, with 9 strains being detected in each isolates. ConclusionThe positive rate of foodborne Salmonella in Minhang District, Shanghai, is high in summer and autumn, with a higher infection rate among retired people and those aged 60 years and above being the high-risk group. It is recommended to strengthen the protection for high-risk groups, implement targeted prevention and control measures in summer and autumn to reduce the risk of infection, and pay attention to guiding clinical medication and infection control.

AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1～4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.

Objective To observe the effectiveness and safety of DiaSphere embolized microsphere TACE for treating primary hepatocellular carcinoma(HCC).Methods Totally 188 patients with HCC were prospectively enrolled and randomly assigned to research group(n=93)and control group(n=95),who underwent TACE with DiaSphere embolized microspheres and Embosphere embolized microspheres,respectively.The incidence of TACE-related adverse events were recorded.The therapeutic efficacy 1 month after the first TACE,also 1 and 3 months after the last TACE,and liver functions 1 month after the first and last TACE were compared between groups.Results In research group,there were 69 cases underwent 1 time TACE,22 cases underwent 2 times and 2 cases underwent 3 times TACE,while in control group,there were 82 cases underwent 1 time and 13 cases underwent 2 times TACE,respectively.No statistical difference of the incidence of adverse events was found between groups(77.42%[72/93]vs.76.84%[73/95],P=1.000).One month after the first TACE,7 cases in research group and 11 cases in control group were lost to follow-up,respectively.One month after the last TACE,12 cases were lost to follow-up in both groups,and 3 months after the last TACE,28 cases were lost to follow-up in both groups.No significant difference of objective response rate nor disease control rate was found between groups at the above time points(all P＞0.05).One month after the first and last TACE,liver function indicators were not different between groups(all P＞0.05).Conclusion Both the short-term efficacy and safety of TACE with DiaSphere embolized microspheres for treating HCC were good.