Objective To explore the relationship between haptoglobin gene polymorphism and disease se-verity and susceptibility in senile vascular dementia patients.Methods A total of 80 patients with senile vas-cular dementia admitted to the hospital from February 2018 to February 2023 were selected as the vascular de-mentia group,and 80 stroke patients with non-vascular dementia admitted to the hospital during the same pe-riod were selected as the control group.The genotype distribution and allele frequency of haptoglobin gene were measured using polymerase chain reaction with sequence-specific primers,and their relationship with the severity and susceptibility of vascular dementia patients was analyzed.Results The proportion of history of hyperlipidemia and diabetes mellitus and the levels of total cholesterol and triglyceride in vascular dementia group were higher than those in control group,the differences were statistically significant(P＜0.05).The distribution of genotypes was in Hardy-Weinberg equilibrium(P＞0.05).The frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele in vascular dementia group were higher than those in control group,and the differences were statistically significant(P＜0.05).There were significant differences in the scores of mini-mental state examination and hachinski ischaemic score among patients with vascular dementia with different haptoglobin genotypes(P＜0.05).Multivariate Logistic regression analysis showed that the carrier of hapto-globin 2-2 genotype and the carrier of haptoglobin 2 allele were independent risk factors for vascular dementia(P＜0.05).Conclusion Haptoglobin 2-2 genotype and haptoglobin 2 allele distribution frequency are associ-ated with the occurrence of vascular dementia after stroke,and those with high frequency of haptoglobin 2-2 genotype and haptoglobin 2 allele distribution suffer a severe disease,which can provide reference for early i-dentification and assessment of vascular dementia.

Objective To investigate the predictive value of inflammatory cells and clinical features in the prognosis of immune checkpoint inhibitors (ICIs) treating non-small cell lung cancer (NSCLC).Methods The data of 163 cases of stage Ⅲ and Ⅳ NSCLC patients treated with the ICIs in this hospital from January 1,2017 to December 31,2022 were collected.The CT examination was conducted after 6-8 weeks treatment.The pa-tients were divided into the objective remission group[complete remission (CR)+partial remission (PR)]and non-objective remission group[stable disease (SD)+progressed disease (PD)],disease control group (CR+PR+SD) and non-disease control group (PD),persistent clinical benefit group (DCB) and non-DCB group.The differences in clinical features and inflammatory cells indicators were compared among the differ-ent groups.The receiver operating characteristic (ROC) curve was adopted to evaluate the predictive efficiency of the inflammatory cells indicators for DCB.The influencing factors analysis of progression free survival (PFS) time and overall survival (OS) time adopted the Cox regression analysis.Results The lymphocyte count (ALC) in the disease control group was higher than that in the non-disease control group.The neutro-phil to lymphocyte ratio (NLR),platelet-lymphocyte ratio (PLR) and mononuclear lymphocyte ratio (MLR) were lower than those in the non-disease control group.The proportions of squamous cell carcinoma,stage Ⅲ,ECOG score 0-1 point,adverse reactions in the DCB group were higher than those in the non-DCB group (P<0.05),the PLT count,NLR,PLR and MLR were lower than those in the non-DCB group (P<0.05). The ROC curve analysis results showed that PLT,NLR,PLR and MLR could serve as the indicators for pre-dicting DCB,the area under of ROC curve (AUC) was 0.633,0.602,0.635 and 0.604 respectively,the opti-mal cut off values were 187×109/L (P=0.004),5.0 (P=0.026),235 (P=0.003) and 0.35 (P=0.024) re-spectively.The multivariate Cox regression analysis showed that non-squamous carcinoma including adenocar-cinoma (HR=1.565,95％CI:1.057-2.316) and other pathologic types (HR=2.285,95％CI:1.326-3.936),ECOG score 2-3 points (HR=2.375,95％CI:1.652-3.415),AMC≥0.65×109/L (HR=1.847,95％CI:1.160-2.938) and PLR≥235 (HR=1.557,95％CI:1.016-2.386) were the independent risk factors for short PFS.The ECOG score 2-3 points (HR=4.615,95％CI:2.882-7.391),AMC≥0.65×109/L (HR=5.161,95％CI:2.984-8.925) and PLR ≥235 (HR=1.732,95％CI:1.059-2.833) were the independent risk fac-tors for short OS (P<0.05),and having adverse reactions (HR=0.472,95％CI:0.294-0.757) was the independ-ent protective factor for short OS (P<0.05).Conclusion Lower PLT,AMC,NLR,MLR and PLR,higher ALC,squamous cell carcinoma,TNM stage Ⅲ,ECOG score 0-1 point and immunotherapy related adverse reactions could prompt that the prognosis is good in ICIs treating advanced NSCLC.PLT,NLR,PLR and MLR could serve as the indicators for predicting DCB.

Objective To compare the diagnostic value of ultrasound,thyroglobulin measurement in fine-needle aspiration biopsy(FNA-Tg),and their combination in the diagnosis of cervical lymph node metastasis in papillary thyroid carcinoma(PTC).Methods The clini-cal data of 130 patients(144 lymph nodes in total)with PTC in Tangshan Gongren Hospital from January 2017 to March 2023 were retro-spectively analyzed.Patients were divided into metastatic and non-metastatic groups according to the pathological findings of the cervical lymph nodes.The ultrasonic characteristics,serum Tg,and eluate Tg levels were compared between the two groups.The diagnostic efficacy of ultrasound,FNA-Tg,and the combination for cervical lymph node metastasis was assessed using the receiver operating characteristic(ROC)curve.Results Among 144 cervical lymph nodes,64 comprised the metastatic group and 80 comprised the non-metastatic group.Compared with the non-metastatic group,the lymph nodes in the metastatic group had indistinct cortical-medullary demarcation,uneven echogenicity,cystic changes,microcalcifications,and abnormal blood flow,and the differences were statistically significant(all P＜0.05);however,there was no statistically significant difference between the two groups in transverse to longitudinal ratios and whether the margins were clear(all P＞0.05).Serum Tg in the metastatic and non-metastatic groups was 19.5(1.9-70.7)ng/mL and 20.4(8.9-38.3)ng/mL,respectively,and the difference between the two groups was not statistically significant(P＞0.05);eluate Tg in the metastatic and non-metastatic groups was 500.0(49.4-500.0)ng/mL and 2.4(0.6-6.5)ng/mL,and the difference between the two groups was statisti-cally significant(P＜0.05),with an optimal FNA-Tg critical value of 11.7 ng/mL.FNA-Tg diagnosed cervical lymph node metastasis with the highest specificity,accuracy,and positive predictive value,whereas the combination of ultrasound and FNA-Tg diagnosed cervical lymph node metastasis with the highest sensitivity and negative predictive value.Conclusion Ultrasound manifestations of PTC cer-vical meta-static lymph nodes include poorly demarcated corticomedullary stroma,uneven echogenicity accompanied by cystic changes,microcalcifications,and abnormal blood flow and have high diagnostic efficacy for PTC metastatic lymph nodes.When PTC cervical lymph node abnormalities are suspected on ultrasound,further FNA-Tg should be performed.The combination of ultrasound with FNA-Tg could improve the diagnostic efficacy of PTC cervical lymph node metastasis.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

Objective:To study the clinical value of left ventricle Tei index in evaluating hemodynamics after interventional therapy of patent ductus arteriosus (PDA).Methods:From May 2017 to May 2019, 50 children with PDA who underwent interventional therapy (PDA group) and 27 healthy children (healthy control group) in Anhui Provincial Children’s Hospital were selected. The left ventricle Tei index, plasma brain natriuretic peptides (BNP), left ventricular end-diastolic dimension (LVDD), left ventricular ejection fraction (LVEF) were compared between 2 groups.Results:The left ventricle Tei index was not correlated with heart rate and age in 2 groups ( P>0.05). The left ventricle Tei index before operation in PDA group was significantly lower than that in healthy control group: 0.20(0.16, 0.25) vs. 0.27(0.20, 0.30), and there was statistical difference ( P<0.05). In PDA group, the left ventricle Tei index immediately, 3 d, 1 month and 3 months after operation was significantly higher than before operation: 0.38(0.29, 0.47), 0.32(0.26, 0.40), 0.30(0.27, 0.35) and 0.32(0.26, 0.37) vs. 0.20(0.16, 0.25), and there was statistical difference ( P<0.05); the plasma BNP immediately after operation was significantly lower than before operation: 288 (126, 433) ng/L vs. 582 (303, 1 675) ng/L, and there was statistical difference ( P<0.05); the LVDD 3 months after operation was significantly lower than before operation: (3.03 ± 0.54) cm vs. (3.38 ± 0.51) cm, and there was statistical difference ( P<0.05); the LVEF immediately after operation was significantly lower than before operation: (54.24 ± 6.09)% vs. (59.45 ± 5.93)%, the LVEF 1 and 3 months after operation was significantly higher than that immediately after operation: (63.18 ± 4.71)% and (65.46 ± 4.78)% vs. (54.24 ± 6.09)%, and there were statistical differences ( P<0.05). The left ventricle Tei index before operation was negatively correlated with inner diameter of PDA and plasma BNP ( r = -0.362 and -0.388, P = 0.013 and 0.009), and there was no correlation between LVDD and LVEF ( r = -0.192 and -0.283, P = 0.229 and 0.053); the differences of Tei index before operation and immediately after operation (ΔTei) was positively correlated with inner diameter of PDA ( r = 0.325, P = 0.030), and there was no correlation with BNP, LVDD and LVEF ( r = 0.234, 0.283 and -0.039, P = 0.126, 0.076 and 0.798). Conclusions:The left ventricle Tei index can quickly and accurately assess the change of hemodynamics after interventional therapy of PDA.

Objective:To investigate the efficacy and safety of programmed death-1 (PD1) inhibitor combined with transcatheter arterial chemoembolization (TACE) in the treatment of huge primary liver cancer.Methods:From June 2016 to December 2019, the clinical data of 31 patients with huge primary liver cancer enrolled in the Central Hospital of Lishui were retrospectively collected and analyzed. The tumor size ranged from 10.1 to 18.8 cm, with an average of (14.2±2.3) cm. The patients were divided into TACE group (TACE treatment, 18 cases) and combined group (one week after TACE, patients receiving a dose of 200 mg PD1 inhibitor administration every 21 days, 13 cases), according to whether patients receiving PD1 inhibitors. The patients were followed up. The disease control rate (DCR) were compared between the two groups using Mann-Whitney U test. The median overall survival (OS) and progression free survival (PFS) were calculated by Kaplan-Meier method. Results:The DCR in combined group (53.8%, 7/13) was higher than that in TACE group (22.2%, 4/18), and the difference was statistically significant ( Z=-2.13, P=0.04). The median PFS (5.0 months) in combined group was longer than that in TACE group (3.0 months), the difference was statistically significant (χ2=4.39, P=0.04). The median OS (15 months) in combined group was longer than that in control group (9 months), and the difference was statistically significant (χ2=5.51, P=0.02). Conclusion:The combine PD1 inhibitors with TACE is an effective and safe therapy for huge primary liver cancer.

Objective:To compare the clinical effects of microwave ablation (MWA) and surgical resection in the treatment of small hepatocellular carcinoma(SHCC).Methods:Sixty five SHCC patients with intact clinical data, treated in the Center of Hepatobiliary Surgery, Peking University People's Hospital between Feb 2005 and Aug 2012, were enrolled in this study. Among them, 30 patients were treated by MWA, and the other 35 by hepatectomy. Follow-up was conducted from Mar 2013 to Feb 2021. The differences in long-term survival, intraoperative blood loss, operative time, postoperative complications, performance status (PS), and postoperative hospital stay were compared between the two groups.Results:The survival probability at 1, 3, 5 and 10 years was 93.2%, 82.5%, 55.6% and 41.2%, respectively, in the MWA group, and 97.1%, 82.6%, 67.2% and 48.3%, in the resection group ( P=0.347). The MWA group had less perioperative complications, less blood loss, shorter operation time, better PS score and better hospital stay than the surgical resection group (all P<0.001).There was no statistically significant difference in the survival rate between BCLC stage 0~A1 and A2~A4 patients( P=0.773, 0.536). Conclusions:Microwave ablation in the treatment of small hepatocellular carcinoma can achieve similar results as hepatectomy with less traumatic,better postoperative PS score and shorter postoperative hospital stay.

Objective:To investigate the efficacy and safety of short-term transcatheter arterial chemoembolization （TACE）-radiofrequency ablation （RFA） sequential therapy for advanced hepatocellular carcinoma (HCC).Methods:The clinical data of 117 patients with advanced HCC enrolled in the Central Hospital of Lishui from March 2010 to January 2019 were retrospectively analyzed. All patients received TACE and RFA sequential therapy. The patients were divided into 2 groups including short interval group (interval≤7 d, 61 cases) and long interval group (interval>7 d, 56 cases) according to interval between TACE and RFA. The difference of response rate was analyzed by Wilcoxon test. Kaplan-Meier survival curve was used to calculate the overall survival (OS) time and progression free survival (PFS) time.The risk factors of TACE-RFA sequential therapy were tested using Cox multivariate analysis. The complications in the two groups were compared using χ 2 test. Results:The response rate in the short interval group (72.1%, 43/61) was significantly higher than that in the long interval group (41.1%，23/56) with significant difference ( Z=-2.50, P=0.01). The median PFS in the short interval group (14.9 months) was longer than that in the long interval group (9.1 months). The difference of PFS survival curve between the 2 groups was statistically significant (χ2 =5.90, P=0.01).The median OS in the short interval group (34.7 months) was longer than that in the long interval group (20.3 months). The difference of OS survival curve between the 2 groups was statistically significant (χ2 =6.60, P=0.01). Cox multivariate analysis showed that tumor size [hazard ratio (HR)=2.42, P<0.01], cirrhosis (HR=2.04, P<0.01), interval (HR=0.44, P<0.01), aspartate aminotransferase (HR=1.71, P=0.03) were the independent risk factors for advanced HCC.There were no significant differences in the complication incidence between the 2 groups ( P>0.05). Conclusion:Short-term interval TACE-RFA sequential therapy as a protective factor is efficient and safe for advanced HCC treatment.

Objective: To investigate the value of contrast-enhanced ultrasound(CEUS) in differential diagnosis of complex renal cysts and clear renal cell carcinoma with cystic change(CRCCC). Methods: The ultrasonographic datas of 82 lesions in 82 patients with complicated renal cysts or CRCCC confirmed by pathology were analyzed. The characteristics of conventional ultrasound and CEUS were observed and evaluated. The lesions were graded according to Bosniak classification criteria. Results: Pathological examination showed that 36 cases were complicated renal cysts and 46 cases were CRCCC. Routine ultrasound showed there were 9 cases (25.0%) with cystic masses and 27 cases (75.0%) with solid and cystic masses in complex renal cysts, of which 14 cases (38.9%) could detect color flow signals. In CRCCC, 2 cases (4.3%) were with cystic masses and 44 cases (95.7%) were with solid and cystic masses, of which 33 cases (75.0%) could detect color flow signals. CEUS showed that only 18 cases (50.0%) of the complex renal cysts showed enhancement of cystic wall or septum, with equal or low enhancement at the peak, 9 cases (50.0%) accompanied by decrease of renal cortex, 35 cases (97.2%) had thin and regular cystic wall, no enhancement of cystic wall in all lesions, and 33 cases (91.7%) had septal thickness less than 1 mm. Forty-five cases (97.8%) of CRCCC showed enhancement of cystic wall or septum, 40 cases (88.9%) showed equal or high enhancement at peak, 30 cases (66.7%) were faster than the decrease of renal cortex, 37 cases (80.4%) showed uneven thickness of cystic wall, 24 cases (52.2%) showed enhancement of cystic wall nodules, and 28 cases (60.9%) showed uneven thickness of septum. After CEUS, 33 cases (91.7%) of complex renal cysts were classified as grade Ⅰ and Ⅱ, while 42 cases (91.3%) of CRCCC were classified as grade Ⅲ and Ⅳ. Conclusions The CEUS manifestations of complex renal cysts are different from those of CRCCC. The application of Bosniak criteria in CEUS is helpful for the differential diagnosis of complex renal cysts and CRCCC.