AIM: To investigate the changes of retinal nerve fiber layer(RNFL)thickness, retinal thickness and blood flow density in different stages of diabetic retinopathy(DR)patients based on optical coherence tomography angiography(OCTA).METHODS: A retrospective analysis was conducted on 382 patients(382 eyes)diagnosed with DR in our hospital from February 2023 to February 2024. According to the staging criteria, the patients were divided into mild group(n=121), moderate group(n=133), severe group(n=72), and proliferative group(n=56). The general clinical data of the four groups of patients was compared; OCTA was used to scan and collect data from all patients, and the RNFL thickness, retinal thickness, and blood flow density were compared among the four groups of patients.RESULTS: There was no statistically significant difference in age, gender, hypertension, chronic kidney disease, and random blood glucose among patients in the mild, moderate, severe, and proliferative groups(all P>0.05). As the stage of DR worsened, the duration of the disease gradually prolonged(P<0.05). The thickness of the RNFL(superior, inferior, temporal, nasal, and average thickness)and retinal thickness significantly increased with the severity of DR(all P<0.001); however, there was no statistically significant difference in inferior RNFL thickness between the moderate and mild groups(P>0.05). The blood flow density in the superficial and deep retinal layers, as well as in the choroidal capillary layer, significantly decreased with the progression of DR(all P<0.05). Nevertheless, there was no statistically significant difference in superficial retinal blood flow density between the moderate and severe groups(P>0.05).CONCLUSION: OCTA can accurately observe the changes in RNFL thickness, retinal thickness, and blood flow density in patients with DR at different stages, which can serve as sensitive indicators for monitoring DR progression.

Background and purpose:Gallic acid(GA)induces tumor cells apoptosis and inhibits angiogenesis.Beyond directly attacking tumor cells,another crucial aspect of GA is its ability to modulate and enhance immune system function.For example,it can improve T cell metabolism,alleviate T cell exhaustion,and promote the formation of memory T cell phenotypes.Although several chimeric antigen receptor T(CAR-T)cells products have gained market approval,the technology still faces significant challenges.These limitations include off-target effects,a predisposition to T cell exhaustion and so on.Moreover,similar to exhaustion,cellular senescence is a major hindrance that impairs T cell function.This study aimed to investigate the effects of GA on the anti-tumor function of CAR-T cells both in vitro and in vivo.We further evaluated the impact of GA on CAR-T cells senescence and memory phenotypes,as well as the impact of GA and CAR-T cells on immune cell infiltration within the tumor microenvironment(TME).Methods:Second-generation CAR targeting mouse glypican 3(GPC3)and human epidermal growth factor receptor 2(HER2)were constructed to generate CAR-T cells.CAR-T cells were co-cultured with GA at a concentration of 5 μg/mL,and flow cytometry was used to assess the senescence status and memory phenotype of CAR-T cells and their killing ability against tumor cells at different effector-to-target ratios.Senescence markers included p53,p21,γ-H2AX and senescence-associated β-galactosidase(SA-β-gal),while CCR7 served as the memory phenotype marker.A subcutaneous tumor model was established to explore the effects of GA on the anti-tumor function of CAR-T cells and immune cell infiltration within the TME.Results:We successfully generated human HER2 and murine GPC3 CAR-T cells,achieving a purity of 30%-50%.GA enhanced the in vitro killing ability of CAR-T cells targeting mouse GPC3 and human HER2(P＜0.001)at different E:T ratios,delayed the senescence of mouse GPC3 CAR-T cells(p53,p21,γ-H2AX,P＜0.05;SA-β-gal,P＜0.001;CCR7,P＜0.001).And GA promoted the differentiation of CAR-T cells toward a memory phenotype(P＜0.001).Additionally,GPC3 CAR-T cells inhibited tumor cell growth(P＜0.05),prolonged mouse survival(P＜0.001),and enhanced the infiltration capacity of CAR-cells(P＜0.001)and endogenous immune cells[CD4+T cells,P＜0.05;CD8+T cells,P＜0.01;natural killer(NK)cells,P＜0.01].Conclusion:GA can enhance the cytotoxic activity of CAR-T cells in vitro,and delay the senescence of CAR-T cells.Furthermore,by modulating TME,GA improved immune cell infiltration,thereby augmenting the overall anti-tumor efficacy of CAR-T cells.

BACKGROUND: High temperatures are known to be associated with an increased risk of self-harm, but the influence of demographic changes and country-level indicators on the burden of heat-related self-harm remains unclear. This study examined the key factors driving changes in self-harm mortality linked to high temperatures and explored their impact at the country level. METHODS: This is an ecological study that analyzes data from the 2021 Global Burden of Disease (GBD) study, the World Bank, and the Climate Research Unit (CRU) were analyzed. Decomposition analyses were used to identify key factors driving changes in high temperature-related self-harm mortality between 1990 and 2021. A panel data model assessed the impact of national indicators on heat-related self-harm mortality. RESULTS: In 2021, 14,885 deaths globally were attributed to heat-related self-harm, a 41.94% increase from 1990, with low-middle SDI regions accounting for 47.84% of these deaths. While the global death rate from heat-related self-harm declined slightly over this period, South Asia and low-middle SDI regions contributed most to the decline. However, population aging exacerbated mortality rates. Demographic and meteorological factors were also linked to heat-related self-harm. CONCLUSION The global decline in heat-related self-harm mortality is largely driven by reductions in females, low-middle SDI regions, and South Asia. However, population aging and growth in these regions have added to the mortality burden, slowing the overall decline. Factors such as population density are also associated with heat-related self-harm. Targeted measures are needed to mitigate heat-induced self-harm more effectively in future.
Humans ; Self-Injurious Behavior/etiology* ; Hot Temperature/adverse effects* ; Global Health/statistics & numerical data* ; Female ; Male ; Adult ; Middle Aged ; Aged ; Young Adult ; Adolescent

Objective To explore the application effect of ultrasound-assisted localization in spinal anesthesia for elderly patients with hip fractures.Methods A total of 114 elderly patients undergoing hip fracture surgery with spinal anesthesia in our hospital from September 2022 to June 2024 were enrolled.The random number table method was applied to allocate participants into two groups:surface anatomical landmark localization group and ultrasound-assisted localization group,with 57 patients in each group.Both groups of patients underwent spinal anesthesia via the paramedian approach for puncture.The first-attempt puncture success rate,success rate of the initial puncture site,number of skin punctures,number of adjusted epidural needle direction,positioning time of the puncture point,puncture time(puncture success time,anesthesia time,and total time),adverse events during the puncture process(nerve hypersensitivity and accidental puncture of the dura mater),spinal anesthesia related complications(back pain,headache,and nerve injury),patient satisfaction and hospital stay were observed and compared between the two groups.The quality of early postoperative recovery was evaluated by using the 15-Item Quality of Recovery(QOR-15)scale at 24 h after surgery.Results The first-attempt puncture success rate in the ultrasound-assisted localization group was 71.9％(41/57),which was significantly higher than that in the surface anatomical landmark localization group[28.1％(16/57),x2=21.930,P=0.000].The success rate of the initial puncture site in the ultrasound-assisted localization group was 87.7％(50/57),which was significantly higher than that in the surface anatomical landmark localization group[54.4％(31/57),x2=15.396,P=0.000].The number of skin punctures and adjusted epidural needle direction in the ultrasound-assisted localization group were 1(1,1)and 0(0,1)times,while in the surface anatomical landmark localization group were 2(1,3)and 3(0,5)times,with statistically significant differences(all P=0.000).The puncture positioning time in the ultrasound-assisted localization group was 2.2(1.7,3.2)min,which was significantly longer than that in the surface anatomical landmark localization group[0.8(0.5,1.2)min,Z=-8.418,P=0.000].The puncture success time,anesthesia time,and total time of the ultrasound-assisted localization group were 1.9(1.7,2.3),4.9(4.3,5.3),and 7.1(6.3,8.7)min,while of the surface anatomical landmark localization group were 5.1(2.3,8.0),7.9(5.7,11.0),and 8.6(6.6,12.0)min,with statistically significant differences(all P＜0.05).There were no statistically significant differences in the incidence of nerve hypersensitivity during operation(3.5％vs.7.0％,x2=0.176,P=0.675),accidental puncture of the dura mater by epidural needles(0％vs.3.5％,P=0.496),postoperative headache(0％vs.3.5％,P=0.496),and back pain(1.8％vs.10.5％,x2=2.435,P=0.119)between the two groups.Both groups of patients showed no symptoms of nerve injury after surgery.There were no statistically significant differences in QOR-15 scores at 24 h postoperatively[119(115,124)points vs.116(112,121)points,Z=-1.858,P=0.063]and length of hospital stay[10.0(9.0,12.5)dvs.10.0(8.0,13.0)d,Z=-0.043,P=0.966]between the two groups.The satisfaction of patients in the ultrasound-assisted localization group was significantly higher than that in the surface anatomical landmark localization group(P=0.004).Conclusion Application of ultrasound-guided localization in spinal anesthesia for elderly patients with hip fractures significantly improves the first-attempt puncture and initial puncture site success rates,reduces skin puncture attempts and adjustments of the epidural needle direction,shortens time of anesthetic procedure,and enhances patient satisfaction,making it highly recommendable for clinical use.

Background and purpose:Gallic acid(GA)induces tumor cells apoptosis and inhibits angiogenesis.Beyond directly attacking tumor cells,another crucial aspect of GA is its ability to modulate and enhance immune system function.For example,it can improve T cell metabolism,alleviate T cell exhaustion,and promote the formation of memory T cell phenotypes.Although several chimeric antigen receptor T(CAR-T)cells products have gained market approval,the technology still faces significant challenges.These limitations include off-target effects,a predisposition to T cell exhaustion and so on.Moreover,similar to exhaustion,cellular senescence is a major hindrance that impairs T cell function.This study aimed to investigate the effects of GA on the anti-tumor function of CAR-T cells both in vitro and in vivo.We further evaluated the impact of GA on CAR-T cells senescence and memory phenotypes,as well as the impact of GA and CAR-T cells on immune cell infiltration within the tumor microenvironment(TME).Methods:Second-generation CAR targeting mouse glypican 3(GPC3)and human epidermal growth factor receptor 2(HER2)were constructed to generate CAR-T cells.CAR-T cells were co-cultured with GA at a concentration of 5 μg/mL,and flow cytometry was used to assess the senescence status and memory phenotype of CAR-T cells and their killing ability against tumor cells at different effector-to-target ratios.Senescence markers included p53,p21,γ-H2AX and senescence-associated β-galactosidase(SA-β-gal),while CCR7 served as the memory phenotype marker.A subcutaneous tumor model was established to explore the effects of GA on the anti-tumor function of CAR-T cells and immune cell infiltration within the TME.Results:We successfully generated human HER2 and murine GPC3 CAR-T cells,achieving a purity of 30%-50%.GA enhanced the in vitro killing ability of CAR-T cells targeting mouse GPC3 and human HER2(P＜0.001)at different E:T ratios,delayed the senescence of mouse GPC3 CAR-T cells(p53,p21,γ-H2AX,P＜0.05;SA-β-gal,P＜0.001;CCR7,P＜0.001).And GA promoted the differentiation of CAR-T cells toward a memory phenotype(P＜0.001).Additionally,GPC3 CAR-T cells inhibited tumor cell growth(P＜0.05),prolonged mouse survival(P＜0.001),and enhanced the infiltration capacity of CAR-cells(P＜0.001)and endogenous immune cells[CD4+T cells,P＜0.05;CD8+T cells,P＜0.01;natural killer(NK)cells,P＜0.01].Conclusion:GA can enhance the cytotoxic activity of CAR-T cells in vitro,and delay the senescence of CAR-T cells.Furthermore,by modulating TME,GA improved immune cell infiltration,thereby augmenting the overall anti-tumor efficacy of CAR-T cells.

Objective To explore the application effect of ultrasound-assisted localization in spinal anesthesia for elderly patients with hip fractures.Methods A total of 114 elderly patients undergoing hip fracture surgery with spinal anesthesia in our hospital from September 2022 to June 2024 were enrolled.The random number table method was applied to allocate participants into two groups:surface anatomical landmark localization group and ultrasound-assisted localization group,with 57 patients in each group.Both groups of patients underwent spinal anesthesia via the paramedian approach for puncture.The first-attempt puncture success rate,success rate of the initial puncture site,number of skin punctures,number of adjusted epidural needle direction,positioning time of the puncture point,puncture time(puncture success time,anesthesia time,and total time),adverse events during the puncture process(nerve hypersensitivity and accidental puncture of the dura mater),spinal anesthesia related complications(back pain,headache,and nerve injury),patient satisfaction and hospital stay were observed and compared between the two groups.The quality of early postoperative recovery was evaluated by using the 15-Item Quality of Recovery(QOR-15)scale at 24 h after surgery.Results The first-attempt puncture success rate in the ultrasound-assisted localization group was 71.9％(41/57),which was significantly higher than that in the surface anatomical landmark localization group[28.1％(16/57),x2=21.930,P=0.000].The success rate of the initial puncture site in the ultrasound-assisted localization group was 87.7％(50/57),which was significantly higher than that in the surface anatomical landmark localization group[54.4％(31/57),x2=15.396,P=0.000].The number of skin punctures and adjusted epidural needle direction in the ultrasound-assisted localization group were 1(1,1)and 0(0,1)times,while in the surface anatomical landmark localization group were 2(1,3)and 3(0,5)times,with statistically significant differences(all P=0.000).The puncture positioning time in the ultrasound-assisted localization group was 2.2(1.7,3.2)min,which was significantly longer than that in the surface anatomical landmark localization group[0.8(0.5,1.2)min,Z=-8.418,P=0.000].The puncture success time,anesthesia time,and total time of the ultrasound-assisted localization group were 1.9(1.7,2.3),4.9(4.3,5.3),and 7.1(6.3,8.7)min,while of the surface anatomical landmark localization group were 5.1(2.3,8.0),7.9(5.7,11.0),and 8.6(6.6,12.0)min,with statistically significant differences(all P＜0.05).There were no statistically significant differences in the incidence of nerve hypersensitivity during operation(3.5％vs.7.0％,x2=0.176,P=0.675),accidental puncture of the dura mater by epidural needles(0％vs.3.5％,P=0.496),postoperative headache(0％vs.3.5％,P=0.496),and back pain(1.8％vs.10.5％,x2=2.435,P=0.119)between the two groups.Both groups of patients showed no symptoms of nerve injury after surgery.There were no statistically significant differences in QOR-15 scores at 24 h postoperatively[119(115,124)points vs.116(112,121)points,Z=-1.858,P=0.063]and length of hospital stay[10.0(9.0,12.5)dvs.10.0(8.0,13.0)d,Z=-0.043,P=0.966]between the two groups.The satisfaction of patients in the ultrasound-assisted localization group was significantly higher than that in the surface anatomical landmark localization group(P=0.004).Conclusion Application of ultrasound-guided localization in spinal anesthesia for elderly patients with hip fractures significantly improves the first-attempt puncture and initial puncture site success rates,reduces skin puncture attempts and adjustments of the epidural needle direction,shortens time of anesthetic procedure,and enhances patient satisfaction,making it highly recommendable for clinical use.

Objective To compare the clinical characteristics of cirrhosis with or without portal vein thrombosis(PVT),and to analyze the therapeutic effect of transjugular intrahepatic portosystemic shunt(TIPS)in treating cirrhosis with or without PVT.Methods The clinical data of 193 patients with cirrhosis complicated by gastrointestinal bleeding,who received TIPS from October 2018 to October 2022,were retrospectively analyzed.According to the presence or absence of PVT before TIPS,the patients were divided into non-PVT group(n=118)and PVT group(n=75).After TIPS,the patients were followed up at one,3,6 months and every 6 months thereafter.The effect of PVT on the clinical characteristics of cirrhosis patients and on the therapeutic efficacy after TIPS were analyzed.Results The success rate of TIPS was 100％in both groups.The proportion of carrying out splenectomy or partial splenic artery embolization(PSE)in PVT group was 26.7％(20/75),which was obviously higher than 13.6％(16/118)in non-PVT group,the difference between the two groups was statistically significant(x2=5.192,P=0.023).In PVT group the preoperative Child-Pugh score,the model of end-stage liver disease(MELD)score and serum sodium model of end-stage liver disease(MELD-Na+)score were(8.1±1.9)points,(9.2±8.0)pointsand(9.2±8.0)points respectively,which in non-PVT group were(7.4±1.9)points,(7.7±5.8)points and(7.7±5.8)points respectively,the differences between the two groups were statistically significant(all P＜0.05).The incidence of overt hepatic encephalopathy in PVT group was 33.3％(25/75),which was strikingly higher than 19.5％(23/118)in non-PVT group,the difference between the two groups was statistically significant(P=0.030).No statistically significant differences in postoperative survival rate,rebleeding rate and stent dysfunction rate existed between the two groups(all P＞0.05).Conclusion For the treatment of cirrhotic patients with PVT complicated by gastrointestinal bleeding,TIPS is clinically safe and effective.In cirrhotic patients with PVT,the worse the liver function is,the higher the incidence of overt hepatic encephalopathy after TIPS will be.

Objective To investigate the mechanism of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair in the treatment of hypertension based on the network pharmacology method and animal experiment verification.Methods(1)TCMSP,BATMAN and TCMIP databases were used to screen the active components and targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair.The hypertension-related targets were obtained by searching the Drugbank,Genecard,TTD and Disgenet databases.The intersection(common target)of the active component target and the target related to hypertension disease was taken,and the obtained intersection target was the potential target of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair for the treatment of hypertension.The active ingredients and their targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair were imported into Cytoscape 3.9.1 software to construct a'Chinese medicines-active ingredients-targets'network and screen key active ingredients.The protein-protein interaction(PPI)network of potential targets was constructed to screen potential core targets.The Metascape platform was used to analyze the GO function and KEGG pathway enrichment of potential targets.The key active components and potential core targets were selected for molecular docking verification.(2)Thirty male spontaneously hypertensive rats(SHR)were randomly divided into model group,western medicine group(Candesartan Cilexetil,0.72 mg·kg-1)and low-,medium-and high-dose groups of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma(2.25,4.50,9.00 g·kg-1).Another male WKY rats were selected as blank group,with 6 rats in each group,once a day for 8 weeks.The systolic blood pressure of rat tail artery was detected before administration and 2,4,6 and 8 weeks after drug intervention.The pathological changes of thoracic aorta were observed by HE staining.The protein expression levels of GRP78,CHOP and Caspase-12 in aorta abdominalis were detected by Western Blot.Results(1)A total of 83 active components of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma were obtained,and 158 potential targets(intersection targets)for the treatment of hypertension were screened out.Five key active ingredients:p-hydroxybenzoic acid,4-hydroxybenzylamine,tanshinone I,tanshinone,γ-sitosterol;6 potential core targets:IL6,TNF,CASP3,JUN,PTGS2,IL1B;GO functional enrichment analysis obtained 1 826 biological process items,89 cell component items,and 199 molecular function items.KEGG pathway enrichment analysis obtained 186 pathways,mainly involving neuroactive ligand-receptor interaction,calcium signaling pathway,inflammatory response(such as TNF and MAPK signaling pathway),vascular protection(such as HIF-1 and cAMP signaling pathway),oxidative stress(such as PI3K-Akt signaling pathway)and other signaling pathways.Tanshinone I and tanshinone had strong binding force to 6 potential core targets,and γ-sitosterol had strong binding force to IL6,CASP3,JUN,PTGS2 and IL1B.(2)Compared with the blank group,the systolic blood pressure of the model group was significantly increased(P＜0.01).The thoracic aortic endothelial injury was obvious,the endothelial cell morphology was abnormal,swelling and exfoliated cells could be seen,the intima of the tissue was disordered,the intima structure was incomplete,and the intima was thickened.The protein expressions of GRP78,CHOP and Caspase-12 in abdominal aorta were significantly increased(P＜0.01).Compared with the model group,the systolic blood pressure of the rats in the administration group was significantly decreased(P＜0.01);the injury of thoracic aorta was alleviated,and the morphology,intima structure and thickness of endothelial cells were improved to varying degrees.The protein expressions of GRP78,CHOP and Caspase-12 in abdominal aorta were significantly decreased(P＜0.01).Conclusion Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair may act on core targets such as IL6,TNF,CASP3,JUN,PTGS2,and IL1B through key active components such as p-hydroxybenzoic acid,tanshinone,and γ-sitosterol,and regulate key signaling pathways such as TNF signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,and PERK signaling pathway to improve vascular endothelial dysfunction,inhibit endoplasmic reticulum stress,and lower blood pressure.

Objective To assess the efficacy and safety of ascending aorta banding technique combined with typeⅠhybrid aortic arch repair for the aortic arch diseases. Methods The clinical data of patients undergoing ascending aorta banding technique combined with type Ⅰ hybrid arch repair for aortic arch diseases from March 2019 to March 2022 in Beijing Anzhen Hospital were retrospectively analyzed. The technical success, perioperative complications and follow-up results were evaluated. Results A total of 44 patients were collected, including 35 males and 9 females, with a median age of 63.0 (57.5, 64.6) years. The average EuroSCORE Ⅱ score was 8.4%±0.7%. The technical success rate was 100.0%. All patients did not have retrograde type A aortic dissection and endoleaks. One patient died of multiple organ failure 5 days after operation, the in-hospital mortality rate was 2.3%, and the remaining 43 patients survived and were discharged from hospital. The median follow-up period was 14.5 (6-42) months with a follow-up rate of 100.0%. One patient with spinal cord injury died 2 years after hospital discharge. One patient underwent thoracic endovascular aortic repair at postoperative 3 months due to new entry tears near to the distal end of the stent. Conclusion Ascending aorta banding combined with typeⅠhybrid arch repair for the aortic arch diseases does not need cardio-pulmonary bypass. Ascending aorta banding technique strengthens the proximal anchoring area of the stent to avoid risks such as retrograde type A dissection, endoleak and migration. The operation owns small trauma, rapid recovery, low mortality and a low rate of reintervention, which may be considered as a safe and effective choice in the treatment of the elderly, high-risk patients with complex complications.