OBJECTIVE To explore the effects of Tianma xiongling zhixuan tablet on autophagy in vascular endothelial cells of rats and its potential mechanism. METHODS The rat aortic endothelial cells （RAECs） were divided into normal group， model group， blank serum group， traditional Chinese medicine （TCM） medicated serum group， autophagy blocker group， autophagy agonist group， and TCM combined with autophagy agonist group. Except for normal group， other groups were given 10 μg/mL lipopolysaccharide for 24 hours to induce RAECs inflammation injury model. Blank serum group was treated with 10% blank serum； TCM medicated serum group received 10% medicated serum derived from Tianma xiongling zhixuan tablet； autophagy blocker group was treated with 20 μmol/L of PD98059； autophagy agonist group was administered 50 μmol/L Honokiol. Lastly， the TCM combined with autophagy agonist group was given both 10% medicated serum derived from Tianma xiongling zhixuan tablet and 50 μmol/L Honokiol. The morphological characteristics of RAECs in each group were observed. The cell viability of each group， the contents of endothelin-1 （ET-1） and nitric oxide （NO）， mitochondrial reactive oxygen species， mitochondrial membrane potential， and the expression levels of PTEN-induced kinase 1 （PINK1）， Parkin， ubiquitin-binding protein （p62）， and microtubule-associated protein 1 light chain 3 （LC3） were detected. RESULTS Compared with model group， the levels of ET-1， mitochondrial reactive oxygen species， and the relative expressions of PINK1， Parkin， and LC3 proteins in the autophagy blocker group and TCM medicated serum group were decreased or down-regulated significantly （P＜0.05 or P＜0.01）； the cell viability rate （only autophagy blocker group）， NO level， mitochondrial membrane potential， and the E-mail：46164660@qq.com relative expression level of p62 protein were increased or up-regulated significantly （P＜0.05 or P＜0.01）； the pathological damage of RAECs was significantly improved， the number of cells increased significantly， and the typical paving stone-like characteristics were restored. The levels of ET-1， mitochondrial reactive oxygen species， and the relative expression levels of Parkin and LC3 proteins in the autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while cell viability rate was decreased significantly （P＜0.05）， the damage of RAECs was aggravated. Compared with the autophagy agonist group， the cell viability rate and the relative expression level of p62 protein in TCM combined autophagy agonist group were increased or up-regulated significantly （P＜0.05 or P＜0.01）， while the levels of ET-1， the relative expression levels of PINK1， Parkin， and LC3 proteins were down-regulated significantly （P＜ 0.01）， the damage of RAECs was reversed to a certain extent. CONCLUSIONS Tianma xiongling zhixuan tablet protects vascular endothelial function by regulating mitochondrial autophagy， the mechanism of which may be associated with the regulation of PINK1/Parkin signaling pathway and the inhibition of mitochondrial autophagy.

Objective:To investigate the clinical efficacy and safety of programmed death protein 1 (PD-1) inhibitos combined with Fuzheng Kang'ai Decoction in patients with stage Ⅲ or Ⅳ non-small cell lung cancer (NSCLC) and identify factors that influence progression and prognosis in real world.Methods:Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), total survival time (OS) and adverse events of patients with advanced or metastatic NSCLC who received PD-1 inhibitors for the first time in the Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine from August 2018 to March 2021 were retrospectively analyzed, and was prospectively followed up until September 2022. Kaplan-Meier method was used to plot survival curves and evaluate median PFS and median OS, while Cox proportional hazards regression model was used for multivariate analysis.Results:The final 66 patients were included in the study, with an ORR of 33.3% (22/66), a DCR of 86.4% (57/66), a median PFS of 9.90 months, and a median OS of 31.83 months. Univariate analysis showed that median PFS was associated with TNM stage, liver metastasis, PD-L1 expression level, lung immune prognostic index (LIPI), and traditional Chinese medicine syndrome types ( P values were 0.004, 0.033, 0.040, 0.004, and 0.001, respectively). Multivariate Cox regression analysis showed that TNM stage [ HR (95% CI)=4.179 (1.781, 9.804)], PD-L1 expression level 1%-49% [ HR (95% CI)=0.346 (0.127, 0.940)] or ≥ 50% [ HR (95% CI)=0.074 (0.019, 0.288)], LIPI [ HR (95% CI)=14.515 (2.939, 71.681)], and TCM characteristics of deficiency of yang qi [ HR (95% CI)=5.954 (2.093, 16.940)] were independent influencing factors for PFS. The overall and grade 3-5 treatment-related adverse events were 68.2% (45/66) and 9.1% (6/66), respectively. Conclusions:Fuzheng Kang'ai Decoction combined with PD-1 inhibitors is an effective and tolerable therapy for patients with advanced or metastatic NSCLC. TNM stage, liver metastasis, PD-L1 expression, LIPI and TCM characteristics are early predictors of clinical efficacy for patients with stage Ⅲ/Ⅳ NSCLC that receive traditional Chinese medicine combined with immunotherapy .

Objective:To investigate the risk factors of olfactory dysfunction (OD) of female patients with primary Sj?gren′s syndrome (pSS) and a prediction model was constructed.Methods:A total of 252 female pSS patients in the Third Municipal Hospital of Huzhou, from January 2021 to 2023 were recruited. According to the olfactory function,they were divided into OD group (144 cases) and without OD group (108 cases).The independent risk factors of OD were evaluated and the clinical prediction efficiency of the model was analyzed by receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test and the decision curve analysis (DCA) curve.Results:The rate of OD was 57.1%((144/252)) in female pSS patients. Hyposmia was the main olfactory disorder in OD group (140/144, 97.2%). Univariate analysis showed that there were significant differences between OD and without OD groups, including disease course ( t=-2.05, P=0.040), RF( t=2.90, P=0.004), IgG( t=4.41, P=0.001), C3( t=5.47, P=0.001), ESSPRI( t=2.55, P=0.011), ESSDAI( t=3.80, P=0.001), HAMD ( t=3.38, P=0.001). Logistic regression analysis showed that high serum RF, IgG and low complement 3, high scores of ESSDAI and HAMD high scores were independent risk factors for pSS patients with OD patients[ OR(95% CI)=1.01(1.01, 1.03), 1.21(1.06, 1.38), 0.98(0.96, 0.89), 1.52 (1.20, 1.92), 1.13(1.03, 1.23)] ( P value were 0.016, 0.005, 0.004, <0.001 and 0.007 respectively). Based on the above independent risk factors, we constructed the prediction model nomogram and performed the internal data validation. The ROC curve AUC (95% CI) of the modeling group was 0.83(0.77, 0.89) and validation group was 0.69(0.57, 0.82), the prediction model was well differentiated.Hosmer-Lemeshow goodness-of-fit test showed that the prediction model had good calibration ability ( P=0.083), and the DCA curve display model is clinically valuable. Conclusion:The clinical prediction model developed in this study can be used to assess the risk of pSS-OD development, which is helpful for early detection and timely interention so can improve the quality of life of pSS-OD patients in turn.

Objective:To determine the effect of miR-122-5p on microglia polarization, apoptosis and inflammation after traumatic brain injury (TBI).Methods:A mouse model and an in vitro TBI model were established. Astrocytes were stimulated to synthesize and release exosomes by brain extracts. microRNA microarray analysis was used to analyze the significantly altered microRNAs. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to detect the expression of miR-122-5p in the in vivo and in vitro TBI model. TUNEL, immunofluorescence, and Western blot were performed to detect the effects of miR-122-5p inhibitors on microglia apoptosis, microglia M1/M2 phenotype transformation and the activation of NLRP3 inflammasome pathway and the phosphorylation of NF-κB after TBI.Results:The results of microRNA microarray analysis showed that 83 miRNAs were downregulated significantly (altered more than 2 folds, P < 0.05), among which miR-122-5p was significantly down-regulated ( P < 0.01). Expression of miR-122-5p was significantly decreased in the in vivo and in vitro TBI model [(1.00±0.00) vs. (0.41±0.15), P < 0.001; (1.00±0.00) vs. (0.34±0.07), P < 0.001]. TUNEL and immunofluorescence showed that miR-122-5p inhibitor significantly alleviated microglia apoptosis[(8.03±1.30) vs. (3.17±0.34), P < 0.001] and promoted microglia M1→M2 phenotype transformation ,M1 phenotype polarization was reduced [(56.96±13.70) vs. (34.70±3.47), P =0.002] and M2 phenotype polarization was increased [(30.46±3.67) vs. (40.74±2.49), P =0.005]. Western blot showed that NLRP3 inflammasome activation was inhibited and NF-κB phosphorylation was decreased when miR-122-5p was downregulated[(0.77±0.10) vs. (0.51±0.11), P =0.02; (0.73±0.08) vs. (0.50±0.07), P =0.003]. Conclusions:miR-122-5p is downregulated in microglia and exosomes secreted by astrocytes after TBI. miR-122-5p inhibitor can attenuate the microglia inflammatory response after TBI by inhibiting the activation of NLRP3 inflammasome pathway and the phosphorylation of NF-κB, promoting the microglia M1→M2 phenotypic transformation and reducing microglia apoptosis, thereby reducing the microglia inflammatory injury after TBI.

Objective:To investigate the correlation between acoustic radiation force impulse imaging(ARFI) and reserve function of liver and the feasibility of liver reserve function assessment by ARFI.Methods:According to the inclusion criteria, 74 patients were screened and 71 patients were finally enrolled from Henan Province People′s Hospital during June 2017 and June 2019. The portal vein diameter (D PV), spleen length (L SP) were measured by two-dimensional ultrasound. The liver shear wave velocity (LSWV) and spleen shear wave velocity (SSWV) were measured by ARFI. Serological markers were checked, and the indocyanine green (ICG)15-minute retention rate (ICG R15) was measured by excretion test. The patients were divided into ICG R15<10% group and ICG R15≥10% group, the difference of the measurements between two groups were calculated, the correlations of the measurements and ICG R15 were analyzed. LSWV diagnostic performance for liver reserve function was evaluated by the ROC curve. Results:There were significant differences in LSWV, D PV, SSWV, L SP, aspartate transaminase(AST), alkaline phosphatase(ALP), y-glutamyl transpeptidase(γ-GGT) and albumin (ALB) between ICG R15<10% group and ICG≥10% group( P<0.05), but no significant differences in other measurements( P>0.05). The correlations between ICG R15 and LSWV( r=0.673, P<0.001), D PV( r=0.355, P<0.05), SSWV( r=0.384, P<0.05), L SP( r=0.403, P<0.001), ALP( r s=0.245, P<0.05) and ALB( r s=-0.390, P<0.05) were statistically significant. The ROC curve showed high diagnostic performance for liver reserve function assessment by LSWV. The area under the ROC curve was 0.903 (95% CI=0.810-0.961, P<0.01), and the cut-off value was 2.15 m/s (sensitivity 84.6%, specificity 86.7%). Conclusions:The LSWV can evaluate the reserve function and it is a useful supplement to the ICG excretion experiment.

Objective:To investigate the characteristics of contrast-enhanced ultrasound (CEUS) in alpha-fetoprotein (AFP)-negative recurrent small hepatocellular carcinoma (rsHCC).Methods:The imaging characteristics of CEUS were retrospectively analyzed in 132 lesions from 116 patients with rsHCC, including 59 lesions from 51 AFP-negative patients and 73 lesions from 65 AFP-positive patients. The hemodynamic parameters such as contrast-enhanced onset time, time-to-peak, isoenhancement start time, low-enhancement start time, and perfusion mode were compared between two groups.Results:The time-to-peak, isoenhancement start time, low-enhancement start time of AFP-negative group were significantly increased than those in AFP-positive group (23.22±5.08)s vs. (20.30±3.41)s, (59.44±39.75)s vs. (40.75±16.16)s, (102.89±44.45)s vs. (87.08±25.27)s (all of P<0.05). Meanwhile, the proportion of isoenhancement during the portal and late phases in AFP-negative group was significantly higher than those in AFP-positive group (59.3% vs. 37.0%, 16.9% vs. 4.1%; all of P<0.05). However, there was no significant difference between the two groups in the enhancement start time (14.87±6.00)s vs. (14.35±5.30)s ( P>0.05) as well as isoenhancement proportion in the arterial phase (94.9% vs. 98.6%, P>0.05). Conclusions:The enhancement pattern of CEUS in AFP-negative rsHCC patients was "fast-in and slow-out" with a diverse and atypical trend. Recognizing its regular features will facilitate the early detection of AFP-negative rsHCC.

Objective:To investigate the characteristics of contrast-enhanced ultrasound (CEUS) in alpha-fetoprotein (AFP)-negative recurrent small hepatocellular carcinoma (rsHCC).Methods:The imaging characteristics of CEUS were retrospectively analyzed in 132 lesions from 116 patients with rsHCC, including 59 lesions from 51 AFP-negative patients and 73 lesions from 65 AFP-positive patients. The hemodynamic parameters such as contrast-enhanced onset time, time-to-peak, isoenhancement start time, low-enhancement start time, and perfusion mode were compared between two groups.Results:The time-to-peak, isoenhancement start time, low-enhancement start time of AFP-negative group were significantly increased than those in AFP-positive group (23.22±5.08)s vs. (20.30±3.41)s, (59.44±39.75)s vs. (40.75±16.16)s, (102.89±44.45)s vs. (87.08±25.27)s (all of P<0.05). Meanwhile, the proportion of isoenhancement during the portal and late phases in AFP-negative group was significantly higher than those in AFP-positive group (59.3% vs. 37.0%, 16.9% vs. 4.1%; all of P<0.05). However, there was no significant difference between the two groups in the enhancement start time (14.87±6.00)s vs. (14.35±5.30)s ( P>0.05) as well as isoenhancement proportion in the arterial phase (94.9% vs. 98.6%, P>0.05). Conclusions:The enhancement pattern of CEUS in AFP-negative rsHCC patients was "fast-in and slow-out" with a diverse and atypical trend. Recognizing its regular features will facilitate the early detection of AFP-negative rsHCC.

OBJECTIVE: To summarize the clinical data of patients who experienced cryoablation in minimally invasive mitral valve surgery and to explore safety and effectiveness of the surgery.
 METHODS: We retrospectively collected the clinical data of patients who experienced cryoablation in minimally invasive mitral valve surgery in Department of Cardiovascular of Second Xiangya Hospital from August 2013 to July 2015. Through a right side (4-6 cm) thoracotomy, femoral cannulation and aortic cross-clamp by Chitwood clamper was performed, left atrium was entered from interatrial groove. Modified left and right side cryomaze followed by valve surgery was finished. The left atrial appendage was excluded by oversewing from endocardial surface. The cardiopulmonary bypass time, cross-clamp time, duration in hospital were recorded. The heart rhythm of 3 consecutive post operation days, at 7th day, 3 months, 6 months, 12 months or 18 months after the surgery was monitered by 12-leads electrical cardiogram.
 RESULTS: No death was observed in this group. Reexploration for bleeding was conducted for one case. Operation time, CBP time and cross-clamp time was (197.4±27.2), (103.6±20.3)and (65.3±15.7) min, respectively. Duration in ICU and hospital was (1.2±0.4) and (9.2±1.6) d, respectively. The ratio of sinus rhythm restoration right after surgery was 97.1%. The ratio of sinus rhythm restoration at the time of hospital discharge was 94.3%. No motality was found in follow-up. The ratio of sinus rhythm restoration at 3, 6, 12,18 months after the surgery was 94.3%, 93.5%, 90.5%, 93.3%, respectively.
 CONCLUSION Right minimal invasive thoracoscopic-assisted cryoablation in mitral valve surgery is quite effective in the treatment of atrial fibrillation, displaying the advantages of less complications, motality and hospitalization.
Aorta ; Atrial Fibrillation ; Cardiac Surgical Procedures ; Cryosurgery ; Heart Atria ; Humans ; Minimally Invasive Surgical Procedures ; Mitral Valve ; Retrospective Studies ; Surgical Instruments ; Thoracotomy

Objective To investigate the therapeutic efficacy of Chinese medicine of Wusheng Tincture for external application in treating cancer pain, and to observe its effect on the quality of life ( QOL) of cancer patients. Methods Eighty-three cancer pain patients were randomized into treatment group (N=42) and control group (N=41). Except 5 cases dropping out for the itch of skin, a total of 78 cases finished the treatment, 40 in the treatment and 38 in the control group. The patients were given the corresponding medicine according to the classification of numerical rating scale ( NRS) scores. In the control group, the patients were treated following the three-step analgestic ladder issued by World Health Organization ( WHO). The treatment group was given external application of Wusheng Tincture on the painful regions based on the same three-step analgestie ladder treatment as that of the control group, the treatment course lasting 7 days. The rating scale NRS scores and QOL scores were observed for the assessment of therapeutic effect and QOL of the two groups. Results (1) On medication day 7, NRS scores in both groups were decreased as compared with those one day before treatment (P<0.01), but the differences between the two groups were insignificant (P>0.05) . (2) The total effective rate of the treatment group was 82.5%, and that of the control group was 68.4%, the difference being significant between the two groups ( P<0.05) . For mild-pain patients, the therapeutic effect of the treatment group was better than that of the control group (P<0.05) . However, the difference of the therapeutic effect for patients with moderate and severe pain was insignificant between the two groups ( P>0.05) . ( 3) On medication day 7, QOL scores were much lower in both groups than those one day before medication, the difference being significant ( P<0.01) . However, the difference of QOL scores between the two groups was insignificant after medication (P>0.05) . Conclusion External application of Wusheng Tincture may have certain therapeutic effect in treating patients with mild cancer pain, but fails in enhancing the effect for patients with moderate and severe pain, either in improving the QOL of cancer pain patients when used together with WHO three-step analgestic ladder.