BACKGROUND: The American Heart Association recently released a new cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the association between LE8 scores and the risk of chronic kidney disease (CKD) remains uncertain. We aimed to explore the association of LE8 scores with new-onset CKD and examine whether socioeconomic deprivation and genetic risk modify this association. METHODS: A total of 286,908 participants from UK Biobank and without prior CKD were included between 2006 and 2010. CVH was categorized using LE8 scores: low (LE8 scores <50), moderate (LE8 scores ≥50 but <80), and high (LE8 scores ≥80). The study outcome was new-onset CKD, ascertained by data linkage with primary care, hospital inpatient, and death data. Cox proportional hazard regression models were used to investigate the association between CVH categories and new-onset CKD. RESULTS: During a median follow-up of 12.5 years, 8857 (3.1%) participants developed new-onset CKD. Compared to the low CVH group, the moderate (adjusted hazards ratio [HR], 0.50; 95% confidence interval [CI]: 0.47-0.53) and high CVH (adjusted HR, 0.31; 95% CI: 0.27-0.34) groups had a significantly lower risk of developing new-onset CKD. The population-attributable risk associated with high vs. intermediate or low CVH scores was 40.3%. Participants who were least deprived ( vs.  most deprived; adjusted HR, 0.75; 95% CI: 0.71-0.79) and with low genetic risk of CKD ( vs.  high genetic risk; adjusted HR, 0.89; 95% CI: 0.85-0.94) had a significantly lower risk of developing new-onset CKD. However, socioeconomic deprivation and genetic risks of CKD did not significantly modify the relationship between LE8 scores and new-onset CKD (both P -interaction >0.05). CONCLUSION Achieving a higher LE8 score was associated with a lower risk of developing new-onset CKD, regardless of socioeconomic deprivation and genetic risks of CKD.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Male ; Female ; Middle Aged ; Genetic Predisposition to Disease/genetics* ; Aged ; Risk Factors ; Adult ; Proportional Hazards Models ; Socioeconomic Factors

Porcine epidemic diarrhea virus (PEDV) is an intestinal coronavirus that can cause porcine epidemic diarrhea, leading to diarrhea, vomiting, weight loss, and even death in piglets. Due to the diversity of PEDV strains, traditional vaccines are difficult to sustainably and effectively prevent and control PEDV. This article reviews the strategies and mechanisms of active substances in regulating intracellular signaling pathways, viral proteins, and microbial metabolites to enhance the host immune function against PEDV. It emphasizes the prevention of PEDV resistance and the potential harm of PEDV breaking through interspecies barriers to the human society, aiming to provide reliable theoretical support for the development of new antiviral drugs or vaccines.
Porcine epidemic diarrhea virus/immunology* ; Animals ; Swine ; Swine Diseases/prevention & control* ; Antiviral Agents/pharmacology* ; Coronavirus Infections/virology* ; Viral Vaccines/immunology* ; Humans ; Signal Transduction

Objectives:To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer.Methods:Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models.Results:The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS ( P＜0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion:Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.

Objective:To investigate the clinical efficacy of different surgical approaches for repairing eyelid coloboma.Methods:Patients with the divided nevus of eyelid treated at Hypospadias Plastic Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2005 to January 2022 were included. The surgeries were categorized into 4 types. (1) Direct excision and suture. (2) Local skin grafts: covering the defect with split- or full-thickness skin grafts according to the size of the defect on the upper and lower eyelids. (3) Combined skin grafts with orbicularis oculi myocutaneous flap: grafting skin flaps for defects on the upper eyelid and near the lower eyelid, and temporal area skin flaps based on the same side orbicularis oculi muscle pedicle for lower eyelid defects. (4) Temporal area expanded flap based on the orbicularis oculi muscle combined with skin grafts: the surgery was divided into two stages, the first stage involves the placement of an expander in the temporal area of the affected side, and the second stage involves the removal of the expander, excision of eyelid lesion tissue and formation of an island-shaped skin flap with the orbital part of the orbicularis oculi muscle pedicle as the pedicle, which was rotated 180° to cover the lower eyelid defect. Defects near the upper and lower eyelid margins were still covered with skin grafts. Follow-up was conducted through outpatient visits, telephone calls, and WeChat messaging to assess facial appearance postoperatively. SPSS 22.0 statistical software was used for analysis, and the measurement data were expressed as Mean±SD, the count data were expressed as percentage, and the comparison of preoperative and postoperative was calculated by aesthetic and functional status of facial soft-tissue deformities (A&F scores) within the group was performed by paired t-test, the difference was considered statistically significant at P<0.05. Results:A total of 34 patients were included; average age was 17.7±15.3 years. The size of the lesions varied from the smallest nevus measuring 0.3 cm × 0.2 cm and the largest measuring 14.0 cm × 14.0 cm. Direct excision with suturing was performed in 6 cases, among which 2 cases received simultaneous double eyelid surgery, the postoperative A&F score (4.54 ± 1.32) was higher than the preoperative (3.28 ± 0.98) score, the difference was not statistically significant ( P>0.05). The skin graft was performed in 10 cases, the postoperative A&F score (5.13 ± 1.59) was higher than the preoperative (2.25 ± 1.59), the difference was not statistically significant ( P>0.05). The skin graft combined with using orbicularis oculi muscle skin flap was performed in 7 cases, the postoperative A&F score of our patients (5.54 ±1.46) was significantly higher than the preoperative (2.18 ±1.61 ), the difference was statistically significant ( P<0.05). The skin graft combined with the expanded temporal area flap based on the orbicularis oculi muscle was performed in 11 cases, the A&F score of our patients after repair (4.95 ±0.60) was improved compared with the preoperative (2.18±1.48) score, and the difference was not statistically significant ( P>0.05). Twenty-eight patients were followed up for 8 to 81 months while 6 cases lost due to change of contact information, among whom three developed secondary ectropion of the lower eyelid, three experienced recurrence of nevi in the incision and grafting area, two exhibited significant pigmentation in the grafting area, and one developed secondary ptosis of the upper eyelid, while the rest of the patients were satisfied with the repair results. Conclusion:Surgical excision is the only effective treatment for eyelid cleft nevi with different clinical presentations. Covering defects on the upper and lower eyelids with different tissue transplantation method can disperse the entire nevus, resulting in more stable long-term repair effects and a more natural appearance. The combination of an orbicularis muscle flap and a free skin graft provides more stable result in the plastic surgery of medium to large eyelid split nevi. Free skin grafting of the upper and lower lids near the margins, and flap grafting of the lower lids are more consistent with the physiological state of the upper and lower lids, and the combination of different tissue grafting method can make the appearance of the face more reasonable.

Indocyanine green ( ICG ) is a water-soluble biological fluorescent contrast agent with infrared absorption and emission characteristics. Indocyanine green angiography ( ICGA ) takes advantage of this biological property. After ICG is injected into the vascular system, the blood flow dynamic map is captured by high-speed photography or real-time photography, which can realize the visualization of vascular structure and tissue blood supply. Currently, ICGA is the only technique for intraoperative quantitative evaluation of flap blood perfusion, and it is widely used in plastic surgery and microsurgery. According to the relevant literature reports at home and abroad in recent years, this review introduced the working principle and method of ICGA and its research progress in evaluating the blood perfusion of pedicled skin flaps. It is considered that this technique still has some limitations in methodology and accuracy of result, and it is still necessary to combine the clinical experience of doctors in the evaluation of tissue perfusion of pedicled skin flaps.

Objectives:To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer.Methods:Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models.Results:The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS ( P＜0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion:Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.

Objective:To investigate the clinical efficacy of different surgical approaches for repairing eyelid coloboma.Methods:Patients with the divided nevus of eyelid treated at Hypospadias Plastic Surgery Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from January 2005 to January 2022 were included. The surgeries were categorized into 4 types. (1) Direct excision and suture. (2) Local skin grafts: covering the defect with split- or full-thickness skin grafts according to the size of the defect on the upper and lower eyelids. (3) Combined skin grafts with orbicularis oculi myocutaneous flap: grafting skin flaps for defects on the upper eyelid and near the lower eyelid, and temporal area skin flaps based on the same side orbicularis oculi muscle pedicle for lower eyelid defects. (4) Temporal area expanded flap based on the orbicularis oculi muscle combined with skin grafts: the surgery was divided into two stages, the first stage involves the placement of an expander in the temporal area of the affected side, and the second stage involves the removal of the expander, excision of eyelid lesion tissue and formation of an island-shaped skin flap with the orbital part of the orbicularis oculi muscle pedicle as the pedicle, which was rotated 180° to cover the lower eyelid defect. Defects near the upper and lower eyelid margins were still covered with skin grafts. Follow-up was conducted through outpatient visits, telephone calls, and WeChat messaging to assess facial appearance postoperatively. SPSS 22.0 statistical software was used for analysis, and the measurement data were expressed as Mean±SD, the count data were expressed as percentage, and the comparison of preoperative and postoperative was calculated by aesthetic and functional status of facial soft-tissue deformities (A&F scores) within the group was performed by paired t-test, the difference was considered statistically significant at P<0.05. Results:A total of 34 patients were included; average age was 17.7±15.3 years. The size of the lesions varied from the smallest nevus measuring 0.3 cm × 0.2 cm and the largest measuring 14.0 cm × 14.0 cm. Direct excision with suturing was performed in 6 cases, among which 2 cases received simultaneous double eyelid surgery, the postoperative A&F score (4.54 ± 1.32) was higher than the preoperative (3.28 ± 0.98) score, the difference was not statistically significant ( P>0.05). The skin graft was performed in 10 cases, the postoperative A&F score (5.13 ± 1.59) was higher than the preoperative (2.25 ± 1.59), the difference was not statistically significant ( P>0.05). The skin graft combined with using orbicularis oculi muscle skin flap was performed in 7 cases, the postoperative A&F score of our patients (5.54 ±1.46) was significantly higher than the preoperative (2.18 ±1.61 ), the difference was statistically significant ( P<0.05). The skin graft combined with the expanded temporal area flap based on the orbicularis oculi muscle was performed in 11 cases, the A&F score of our patients after repair (4.95 ±0.60) was improved compared with the preoperative (2.18±1.48) score, and the difference was not statistically significant ( P>0.05). Twenty-eight patients were followed up for 8 to 81 months while 6 cases lost due to change of contact information, among whom three developed secondary ectropion of the lower eyelid, three experienced recurrence of nevi in the incision and grafting area, two exhibited significant pigmentation in the grafting area, and one developed secondary ptosis of the upper eyelid, while the rest of the patients were satisfied with the repair results. Conclusion:Surgical excision is the only effective treatment for eyelid cleft nevi with different clinical presentations. Covering defects on the upper and lower eyelids with different tissue transplantation method can disperse the entire nevus, resulting in more stable long-term repair effects and a more natural appearance. The combination of an orbicularis muscle flap and a free skin graft provides more stable result in the plastic surgery of medium to large eyelid split nevi. Free skin grafting of the upper and lower lids near the margins, and flap grafting of the lower lids are more consistent with the physiological state of the upper and lower lids, and the combination of different tissue grafting method can make the appearance of the face more reasonable.

Indocyanine green ( ICG ) is a water-soluble biological fluorescent contrast agent with infrared absorption and emission characteristics. Indocyanine green angiography ( ICGA ) takes advantage of this biological property. After ICG is injected into the vascular system, the blood flow dynamic map is captured by high-speed photography or real-time photography, which can realize the visualization of vascular structure and tissue blood supply. Currently, ICGA is the only technique for intraoperative quantitative evaluation of flap blood perfusion, and it is widely used in plastic surgery and microsurgery. According to the relevant literature reports at home and abroad in recent years, this review introduced the working principle and method of ICGA and its research progress in evaluating the blood perfusion of pedicled skin flaps. It is considered that this technique still has some limitations in methodology and accuracy of result, and it is still necessary to combine the clinical experience of doctors in the evaluation of tissue perfusion of pedicled skin flaps.

Purpose To examine the clinicopathologic,immunohistochemical,and molecular genetic characteristics and differential diagnosis of low-grade oncocytic tumor(LOT)of kidney with CK7 positive and CD117 negative,so as to enhance the understanding of this tumor among pathologists.Methods A total of five cases of renal LOT from the First Affiliated Hospi-tal of Soochow University between December 2016 and February 2023 were included in this analysis.The clinicopathological fea-tures,immunophenotype,genetic characteristics,and prognosis were evaluated using HE staing,immunohistochemical staining,and Sanger sequencing.Additionally,relevant literature was re-viewed to supplement the findings.Results Among the cohort of five patients,four were female and one was male,aged 57-70 years with a median age of 65 years and an average age of 64.8 years.Clinical presentation revealed that only the first case exhibited frequent urination accompanied by intermittent lumba-go,while the remaining cases were asymptomatic and incidental-ly discovered.Imaging studies demonstrated space-occupying le-sions with clear boundaries and even internal echoes on B-ultra-sonography,and patchy low-density shadows in the center with obvious edge enhancement on CT.Grossly,the tumor was nodu-lar,with a maximum diameter ranging from 2.1 to 7.6 cm,and an average diameter of 4.04 cm,with a solid section.Micro-scopically,the boundary of LOT was consistently well-defined,with a thick capsule.The arrangement of tumor cells was ob-served to be both dense and sparse,accompanied by fresh bleed-ing foci and proteinoid secretions.Focal lymphocyte aggrega-tion,hepatic plate like and hepatic sinusoid like structures,thick-walled blood vessels,false nodules of tumor cells,and old hemorrhage were also noted.The tumor cells exhibited uniformi-ty in shape,appearing round or polygonal,with eosinophilic and fine granular cytoplasm.The nuclei were of similar size and shape,appearing round or oval with a clear nuclear membrane.The histological features of the tumor included 2-grade small nu-cleoli,perinuclear halos,binuclear cells,and nuclear shrink-age,but no mitotic figures were detected.The immunophenotyp-ic analysis revealed strongly diffuse expression of CK7 in the tumor cells,while CD117 was negative.The Ki67 proliferation index was low.Sanger sequencing identified mutations in mTORC1 pathway genes in four cases,including three mutations in MTOR and one mutation in RHEB.The patients underwent either local or radical nephrectomy,and were followed up for a period ranging from 2 to 52 months,during which all patients re-mained free of recurrence.Conclusion The low-grade,eosino-philic,and rare renal tumor known as LOT exhibits inert behav-ior.At present,the follow-up results show that complete resec-tion of local operation is sufficient,and the prognosis is good.It is important to distinguish this lesion from other eosinophilic re-nal tumors.

Tumor microenvironment(TME)is a complex cellular environment where tumor cells reside,along with various types of cells and extracellular components surrounding the tumor cells.Immune cells are key components of TME,including tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),lymphocytes,regulatory T cells(Tregs),natural killer cells(NK cells),dendritic cells(DCs),and many others.It is worth noting that drug resistance is currently a major factor limiting the efficacy of cancer treatment methods such as chemotherapy,radiotherapy,targeted therapy,and immunotherapy,and a leading cause of treatment failure.Research has found that the development of drug resistance in tumor cells is the result of interactions between tumor cells and TME.Consequently,overcoming drug resistance in tumors caused by TME is considered a significant challenge in cancer treatment.In recent years,with in-depth research into immune cells within TME,significant progress has been made in understanding the specific mechanisms by which immune cells regulate drug resistance in tumor cells.Furthermore,therapeutic strategies that target these immune cells,signaling pathways,or cytokines have been shown to effectively combat tumor drug resistance and enhance the therapeutic outcomes of cancer treatment.This article reviews the research advancements regarding the roles of TAMs,MDSCs,Tregs,and NK cells in tumor drug resistance within TME and discusses the development of targeting strategies to overcome this resistance.Additionally,we explore the relationship of tumor-associated neutrophils(TANs)and B regulatory cells(Bregs)with tumor drug resistance.It is hoped that this review will offer insights and serve as reference for reducing tumor drug resistance and improving the efficacy of anti-tumor therapies.