OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

Objective By comparison with the surgical resection,to evaluate the relapse-free survival(RFS),overall survival(OS),and clinical safety of transcatheter hepatic arterial chemoembolization(TACE)combined with microwave ablation(MWA)in the treatment of early primary hepatocellular carcinoma(HCC).Methods From January 2013 to January 2018 at authors'hospital,51 HCC patients received TACE combined with MWA(TACE+MWA group)and 58 HCC patients received surgical resection(RES group).The HCC lesions were single tumor with diameter ≤7 cm or multiple tumors with stage Ⅰ a-Ⅱ a meeting the"up-to-7"criteria.The postoperative RFS,OS,and clinical safety were compared between the two groups.Results The one-,3-and 5-year RFS in the TACE+MWA group were 84.3％,37.3％and 13.7％respectively,which in the RES group were 67.2％,27.6％and 13.8％respectively.The difference in the one-year RFS between the two groups was statistically significant(P=0.039),and the differences in the 3-and 5-year RFS between the two groups were not statistically significant(P=0.281 and P=0.992,respectively).The one-,3-and 5-year survival rates in the TACE+MWA group were 98％,62.7％and 45.1％respectively,which in the RES group were 94.8％,75.9％and 44.8％respectively,and the differences between the two groups were not statistically significant(P=0.704,P=0.137 and P=0.977 respectively).No treatment-related death occurred in both groups.In the TACE+MWA group,the main complications included transient embolism syndrome,abdominal pain during ablation procedure,and mild to moderate transient elevation of transaminase after treatment.In the RES group,the main postoperative complications included fever,pleural effusion,abdominal effusion,and intraoperative bleeding;and in one patient the postoperative liver function impairment worsened to Child grade C.The average cost of hospitalization in the TACE+MWA group was(39 834.98±6 717.38)Chinese yuan,which in the RES group was(49 042.59±11 810.69)Chinese yuan,the difference between the two groups was statistically significant(P=0.017).The hospitalization length in the TACE+MWA group was 23 days(19-28 days),which in the RES group was 21 days(17-25 days),and the difference between the two groups was not statistically significant(P=0.196).Conclusion For the treatment of early HCC,TACE combined with MWA has reliable curative effect,and also has the advantages of being safe and economical.Therefore,this therapy can be used as a preferred option of non-surgical treatment for single tumor with ≤7 cm diameter or multiple tumors with stage Ⅰ a-Ⅱa meeting"up-to-7"criteria.(J Intervent Radiol,2024,33:488-494)

Objective To discuss the clinical efficacy and safety of hepatic arterial infusion chemotherapy(HAIC)combined with carrelizumab and sorafenib in treating advanced hepatocellular carcinoma(HCC).Methods The clinical data of 36 HCC patients,who were admitted to the Affiliated Nantong Third Hospital of Nantong University of China to receive HAIC combined with carrelizumab and sorafenib from August 2019 to August 2020,were collected.According to modified Response Evaluation Criteria in Solid Tumors(mRECIST),the objective response rate(ORR)and disease control rate(DCR)of the combination therapy were evaluated.The Common Terminology Criteria Adverse Events Version 5.0 developed by American National Cancer Institute was used to evaluate the clinical safety.Results After receiving 4 cycles of FOLFOX-HAIC,the ORR and DCR of the patients were 38.9％and 77.8％respectively.The patients were followed up for 30 months.The median progression-free survival(mPFS)was 306 days(95％CI:242.7-369.3),and the median overall survival(mOS)was 515 days(95％CI:2 482.5-547.5).After HAIC treatment,one patient was successfully changed to surgical operation.The overall incidence of adverse events were 100％.There were 9 adverse events(25％)above grade m,including severe abdominal pain(n=2,5.6％),nausea(n=1,2.8％),vomiting(n=1,2.8％),elevated alanine aminotransferase(n=3,8.3％),elevated aspartate aminotransferase(n=1,2.8％),and death due to pulmonary failure caused by severe immune-induced pneumonia(n=1,2.8％).Conclusion For the treatment of advanced HCC,HAIC combined with carrelizumab and sorafenib has better ORR and DCR with controllable safety,which provides a new option for the treatment of advanced HCC.However,studies with large sample size need to be conducted before its long-term survival benefit of patients can be further validated.

Objective To observe and compare in-hospital and 1-year survival and prognosis of patients with 4b acute myocardial infarction(AMI)caused by early and late stent thrombosis(ST).Methods A total of 302 patients with 4b acute myocardial infarction caused by ST were enrolled in this study from January 2015 to February 2018.ST patients were confirmed by coronary angiography.These patients were divided into two groups:the early ST group(n=26)and the late ST group(n=276)according to the time of ST occurrence.Endpoint events during hospitalization and one year of follow up were compared between the two groups of patients.The primary endpoint events included cardiac death and recurrent AMI.The secondary endpoint events included target lesion revascularization(TLR),re-stent thrombosis,heart failure and stroke.The incidence of no endpoint events was compared between two groups of patients by Kaplan and Meier survival analysis.Cox regression analysis was used to analyze risk factors for endpoint events in patients with type 4b AMI.Results There was no significant difference in the incidence of the primary endpoint events during hospitalization between the two groups(7.7%vs.3.3%,P=0.243).The incidence of heart failure was higher in the early ST group than that of the late ST group(11.5%vs.1.4%,P=0.016).There was no significant difference in the incidence rates of other secondary endpoint events between the two groups(P＞0.05).After a mean follow-up of 1 year,the incidence rates of primary endpoint events and the secondary eendpoint events were higher in the early ST group(20.0%vs.5.9%,P＜0.05 and 36.0%vs.11.5%,P＜0.01)than that of the late ST group.Kaplan and Meier survival analysis showed that the 1-year cumulative incidences of non-primary(P= 0.022)and non-secondary events(P＜0.001)were lower in the early ST group than those of the late ST group.Cox regression analysis showed that hypertension and history of coronary artery bypass grafting were independent risk factors for primary endpoint events in patients with 4b AMI,and intraoperative implantation of intraaortic balloon pump(IABP)and shortening the time from stent thrombosis to balloon dilation(ST to B)were independent protective factor.Conclusion Early ST patients have similar in-hospital outcomes and poor long-term prognosis compared with late ST induced 4b type AMI patients.Intraoperative implantation of IABP and shortening of ST to B time may improve the prognosis of 4b type AMI patients.

Objective:To discuss the relationship between 18F-FDG PET/CT metabolic parameters and clinical pathological indicators and prognosis in cutaneous malignant melanoma (CMM). Methods:A total of 100 CMM patients (62 males, 38 females, age (56.5±2.5) years) who underwent 18F-FDG PET/CT scans at the Second Xiangya Hospital of Central South University from August 2013 to November 2022 were retrospectively enrolled. Clinical pathological indicators (such as primary site, TNM staging, sentinel lymph node (SLN) status) and metabolic parameters (SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG), whole-body MTV (wb-MTV), and whole-body TLG (wb-TLG)) were collected. ROC curve analyses were used to determine the PET parameters thresholds for progression-free survival (PFS) and melanoma-specific survival (MSS). Kaplan-Meier survival analysis, univariate and multivariate Cox proportional hazards regression models were used to analyze the prognosis of patients′ PFS and MSS, and a nomogram survival prediction model was constructed. Results:Results of ROC curve analyses showed that the thresholds of SUV max of primary tumor (p-SUV max), MTV of primary tumor (p-MTV), TLG of primary tumor (p-TLG), wb-MTV and wb-TLG for predicting PFS and MSS were 7.13, 2.24 cm 3, 6.98 g, 2.57 cm 3, 8.04 g and 9.09, 2.34 cm 3, 7.44 g, 2.24 cm 3, 9.17 g, respectively. Results of univariate analysis indicated that several clinical pathological indicators and metabolic parameters were prognostic risk factors for PFS and MSS. Results of multivariate analysis indicated that metastases of SLN (hazard ratio( HR)=2.54, 95% CI: 1.09-5.90; P=0.030) and wb-TLG>8.04 g( HR=2.58, 95% CI: 1.17-5.72; P=0.019) were independent prognostic risk factors for PFS, while metastases of SLN ( HR=4.53, 95% CI: 1.54-13.35; P=0.006) and wb-TLG>9.17 g ( HR=2.48, 95% CI: 1.26-4.89; P=0.009) were independent risk prognostic factors for MSS. A nomogram survival prediction model based on PET metabolic parameter (wb-TLG) and clinical pathological indicator (SLN status) can effectively predict the prognosis of CMM patients. Conclusions:Clinical pathological parameters and PET parameters are associated with the prognosis of CMM patients. SLN status is critical for prognosis.

Objective:To investigate the efficacy of 99Tc m-pyrophosphate (PYP) SPECT imaging for the differential diagnosis of transthyretin-related cardiac amyloidosis (ATTR-CA) and hypertrophic cardiomyopathy (HCM). Methods:Data of patients who were definitively diagnosed with ATTR-CA (35 patients (28 males, 7 females); age 62.5(58.6, 64.3) years) or HCM (14 patients (13 males, 1 female); age 60.5(57.3, 68.7) years) by extracardiac biopsy and echocardiography in the Second Xiangya Hospital of Central South University between June 2020 and March 2023 were retrospectively analyzed. All patients underwent planar and SPECT imaging 1 h after injection of 370-720 MBq 99Tc m-PYP. Visual scoring was performed (0-1 was negative, 2-3 was positive), and heart-to-contralateral lung uptake ratio (H/CL) was calculated based on planar images. The χ2 test was used to compare the difference in visual scores between ATTR-CA and HCM groups, and the diagnostic efficacy of the visual score was calculated. The H/CL differences between ATTR and HCM groups were compared with Mann-Whitney U test, and the ROC curve was used to analyze the efficacy of H/CL for the differential diagnosis of ATTR-CA and HCM. Results:There were 34 patients with visual scores≥2 and 1 patient with visual score<2 in the ATTR-CA group, 6 patients with visual scores =2 and 8 patients with visual scores <2 in HCM group, and there were significant differences between the 2 groups ( χ2=16.20, P<0.001). The diagnostic sensitivity of the visual score was 97.1%(34/35), and the specificity was 8/14. The H/CL in the ATTR-CA group was significantly higher than that in the HCM group (2.08(1.97, 2.20) vs 1.26 (1.17, 1.35), z=-5.09, P<0.001). The ROC curve analysis suggested that the optimal cut-off value was 1.45 (AUC: 0.980, 95% CI: 0.946-1.000; P<0.001); the sensitivity of H/CL differential diagnosis between HCM and ATTR-CA was 97.1%(34/35), and the specificity was 14/14. Conclusion:99Tc m-PYP SPECT imaging is useful in differentiation of ATTR-CA and HCM, and the optimal cut-off value of H/CL for differential diagnosis of these 2 diseases is 1.45.

Objective:To evaluate the diagnostic value of PSA and the f/t PSA ratio in prostate cancer screening in Chinese people.Methods:Original articles on the application of PSA and f/t PSA ratio in prostate cancer screening among Chinese population were retrieved from Pubmed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang data and VIP databases from the establishment of the database to June 2023. The literature quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2(QUADAS-2) tool. A meta-analysis was performed with Stata 15.1 software.Results:A total of 26 articles were included, encompassing 18 407 individuals, of whom 4 095 were diagnosed with prostate cancer based on biopsy and postoperative pathological examination, while the rest were patients with other prostate diseases or healthy individuals. 24 used a PSA threshold of>4.0 ng/ml as the cutoff for prostate cancer screening, the pooled sensitivity was 0.88(95% CI: 0.84-0.91), the specificity was 0.42(95% CI: 0.34-0.50), and the area under the summary receiver operating characteristic (SROC) curve (AUC) was 0.7(95% CI: 0.73-0.81). Four articles considered a PSA threshold of>10.0 ng/ml for prostate cancer screening (three of which used the above two cutoff values), the pooled sensitivity was 0.83(95% CI: 0.74-0.89), the specificity was 0.67(95% CI: 0.45-0.84), and the AUC of the SROC was 0.79(95% CI: 0.75-0.83). Eleven articles used the f/t PSA ratio as a screening tool for prostate cancer. When the f/t PSA ratio was<0.16, the pooled sensitivity was 0.82(95% CI: 0.76-0.87), the specificity was 0.76(95% CI: 0.67-0.83), and the AUC of the SROC was 0.86(95% CI: 0.83-0.89). Conclusion:In the screening for prostate cancer in China, PSA has a relatively high sensitivity, and the f/t PSA ratio has a better specificity. Combined application of the two indices is recommended.

Objective:To observe the efficacy of cosmetic suturing techniques combined with topical recombinant human basic fibroblast growth factor (rh-bFGF) in repairing facial trauma.Methods:A prospective study was conducted on 140 patients with facial trauma admitted to the Department of Burn and Plastic Surgery, Northern Jiangsu People＇s Hospital from January to December 2022. Patients were divided into two groups based on different treatment methods using a random number table method: treatment group (70 cases), including 38 males and 32 females aged 3 to 54 (23.1±8.2) years, received cosmetic suturing techniques combined with topical rh-bFGF for wound repair; control group (70 cases), including 36 males and 34 females aged 2 to 49 (22.3±7.5) years, only received cosmetic suturing techniques for wound repair. Patients were followed up 2 weeks post-surgery to evaluate wound healing quality. Patient satisfaction was assessed using the visual analogue scale (VAS). Six months post-surgery, scar conditions were evaluated using the Vancouver scar scale (VSS).Results:In the treatment group, 65 cases were directly sutured, and 5 cases were repaired with skin flaps, with a first-class healing rate of 100% (70/70). In the control group, 66 cases were directly sutured, and 4 cases were repaired with skin flaps, with a first-class healing rate of 91.4% (64/70). The first-class healing rate in the treatment group was higher than that in the control group, with a statistically significant difference ( P=0.037). Two weeks post-surgery, the VAS score for surgical satisfaction in the treatment group was (1.13±0.52) scores, which was lower than that in the control group (2.56±1.32) scores, with a statistically significant difference ( P<0.001). Six months post-surgery, the VSS score for the treatment group was (2.49±1.27) scores, which was lower than that in the control group (4.67±1.93) scores, with a statistically significant difference ( P<0.001). Conclusions:In repairing facial trauma, the combination of cosmetic suturing techniques and topical rh-bFGF can improve wound healing quality, reduce wound scarring, and enhance patient satisfaction with surgery.

Background: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. Methods: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. Results: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. Conclusion BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

OBJECTIVE: To explore the prognosis and influencing factors of ST-segment elevation myocardial infarction (STEMI) due to late stent thrombosis (LST) and very late stent thrombosis (VLST). METHODS: Patients who underwent percutaneous coronary intervention (PCI) for STEMI caused by LST and VLST at Tianjin Chest Hospital from January 2016 to June 2021 were selected as the study subjects, and long-term follow-up was conducted. The baseline clinical features, laboratory examination indicators, echocardiography results, coronary angiography and intervention treatment characteristics, and antiplatelet treatment status of patients were collected. The study endpoint was major adverse cardiovascular event (MACE), including all-cause mortality, target vessel revascularization (TVR), myocardial infarction, and recurrent stent thrombosis (RST). Patients were divided into MACE group and non-MACE group based on the occurrence of MACE. Cox regression analysis was used to determine the univariate and multivariate predictive factors for MACE occurrence in STEMI patients caused by LST and VLST during long-term follow-up after PCI. Kaplan-Meier survival curves were plotted to analyze the cumulative survival rate without MACE during follow-up in subgroups of patients with different levels of fibrinogen (Fib) and initial number of stents. The incidence of MACE among patients receiving different drug-eluting stent (DES) treatments was compared. RESULTS: A total of 418 patients diagnosed STEMI caused by LST and VLST through coronary angiography were enrolled, of which 115 had MACE and 303 did not. Among them, 404 cases (96.65%) completed follow-up, with a median follow-up time of 27.25 (18.00, 37.00) months. Cox regression analysis showed that Fib [hazard ratio (HR) = 2.840, 95% confidence interval (95%CI) was 1.329-6.066, P = 0.007], non-culprit vascular stenosis > 50% (HR = 5.974, 95%CI was 1.634-21.848, P = 0.007), initial stent quantity (HR = 3.314, 95%CI was 1.677-6.552, P = 0.001), B2/C lesions (HR = 5.463, 95%CI was 1.396-21.373, P = 0.015), and cardiogenic shock (HR = 4.141, 95%CI was 1.101-15.568, P = 0.035) were independently associated with the occurrence of MACE. The Kaplan-Meier survival curve showed that the higher the Fib level, the lower the cumulative survival rate without MACE (82.8%, 70.1%, 40.5%, P < 0.01); the more initial stents, the lower the cumulative survival rate without MACE (75.0%, 57.7%, 36.5%), with patients with initial stents ≥ 3 having the lowest cumulative survival rate without MACE (P < 0.001). A total of 210 patients (50.2%) received secondary stent treatment, and there was no significant difference in the incidence of MACE between patients receiving first and second generation DES treatment (27.3% vs. 24.7%, P > 0.05), but patients receiving first generation DES had a higher proportion of all-cause mortality (22.3% vs. 10.1%, P < 0.05). Compared with patients receiving smaller diameter DES treatment (< 2.75 mm), patients receiving larger diameter DES treatment (≥2.75 mm) had a significantly lower incidence of MACE (20.5% vs. 35.9%, P < 0.05). CONCLUSIONS Long-term clinical outcomes after PCI for STEMI due to LST and VLST are unfavorable, with a high rate of MACE. The treatment of this particular type STEMI remains challenging, re-implantation of second generation DES or a larger diameter DES (≥2.75 mm) may be beneficial.
Humans ; Percutaneous Coronary Intervention/methods* ; ST Elevation Myocardial Infarction/therapy* ; Stents ; Prognosis ; Thrombosis/etiology* ; Female ; Male ; Coronary Angiography ; Treatment Outcome ; Risk Factors ; Middle Aged ; Drug-Eluting Stents ; Proportional Hazards Models