Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

OBJECTIVE To systematically evaluate the therapeutic effect of acupuncture on geriatric insomnia.METHODS Randomized controlled trials(RCTs)on acupuncture in the treatment of senile insomnia were searched in CNKI,VIP,Wanfang,China Biomedical Database,PubMed,Web of science,Embase and Cochrane Library databases from inception dates to June 24,2024.Litera-ture was screened and data were extracted based on the inclusion and exclusion criteria.The literature quality was evaluated according to the risk of bias table recommended by the Cochrane Collaboration Handbook 5.1.0,and the outcome indicators were graded using the GRADE system for the quality of evidence.RevMan5.4 software was used to evaluate the quality of the included literature,and Sta-ta18.0 software was used to conduct Meta-analysis on the included literature.RESULTS A total of 18 studies involving 1399 pa-tients were included.Meta-analysis showed that:compared with the simple western medicine treatment,acupuncture in the treatment of senile insomnia patients could improve the clinical effective rate[RR=1.18,95%CI(1.13,1.24),P<0.001],reduce the total PSQI score[MD=-1.10,95%CI(-1.25,-0.96),P<0.001],daytime dysfunction[MD=-1.38,95%CI(-1.59,-1.16),P<0.001],sleep latency[MD=-0.66,95%CI(-0.86,-0.47),P<0.001],sleep duration[MD=-0.45,95%CI(-0.64,-0.25),P<0.001],sleep efficiency[MD=-0.69,95%CI(-0.89,-0.49),P<0.001],sleep disorder[MD=-1.24,95%CI(-1.47,-1.01),P<0.001],sleep quality[MD=-0.84,95%CI(-1.05,-0.64),P<0.001].GRADE classification showed that the clinical efficacy was advanced evidence;the adverse reactions were intermediate evidence;the total score of PSQI,daytime dysfunction,sleep latency,sleep efficien-cy,sleep quality and sleep disorder were low evidence;sleep time was extremely low evidence.CONCLUSION Acupuncture inter-vention in senile insomnia patients is superior to the control group in clinical efficiency and various PSQI scores.Acupuncture interven-tion is worthy of further promotion and use in clinical practice as the complementary and alternative therapy for the conventional western medication treatment of senile insomnia.However,the evidence levels of some outcome indicators are relatively low,and more high-quality RCTs with large sample sizes are still needed to increase the strength of evidence.

In the past, the use of neoadjuvant androgen deprivation therapy (ADT) for prostate cancer did not exhibit survival benefits and was not recommended by the practicing guidelines. In recent years, with the emergence of novel hormonal therapeutics such as Abiraterone, Enzalutamide, Apalutamide and Darolutamide, the interest for neoadjuvant therapy has been reignited. Here, we summarize the four categories of neoadjuvant therapy with new hormonal agents, and discuss how to evaluate the efficacy and explore the molecular mechanism after neoadjuvant therapy.

Objective:To analyze the correlation between the Naples prognostic score (NPS) after preoperative neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC) and evaluate the prognostic value of NPS in LARC.Methods:136 patients with LARC meeting the recruitment criteria from 2015 to 2020 were selected. Serum albumin, total cholesterol (TC) were collected and neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio were calculated. All patients were scored and graded according to the NPS rule. The survival rate was calculated with Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox models. Results:There was no significant correlation between NPS score and tumor regression or pathological complete response (pCR) of LARC patients after neoadjuvant therapy ( P=0.192, P=0.163). However, Cox multivariate analysis showed that NPS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) of LARC ( P=0.009, P=0.003), and hierarchical analysis suggested that LARC patients with lower NPS score obtained better prognosis. Besides NPS, tumor size was also an independent risk factor for OS, and tumor size and N stage were the independent risk factors for DFS. Conclusion:NPS has no correlation with tumor regression or pCR for LARC after neoadjuvant chemoradiotherapy, whereas it could serve as an effective predictor for long-term prognosis of LARC.

Objective To investigate the differences in mechanical properties of the sclera in different regions. Methods The sclera of sus scrofa was divided into 3 regions, namely, anterior, equatorial and posterior area. Local indentation was performed on different areas of the whole sclera. Strip specimens of different regions were circumcised along the equatorial direction, and subjected to uniaxial stretching by INSTRON 5544. Results Within the normal physiological stress range, the stiffness at anterior, equatorial, and posterior area of the sclera measured by local indentation was (0.91±0.21), (0.6±0.16), (0.39±0.13) MPa, respectively. The elastic modulus at anterior, equatorial, and posterior area of the sclera measured by uniaxial stretching was (1-28±0.37), (0.95±0.31), (0.72±0.28) MPa, respectively. Conclusions The local indentation could reflect regional mechanical properties of the sclera. The anterior sclera performed a higher stiffness than the equatorial and posterior areas. The results provide references for further study on the pathogenesis of ocular diseases including myopia.

To review the literatures on the treatment of COPD combined with anxiety and depression treated by TCM in recent years, which conclude that to treat this kind of disease is usually by taking drugs, as well as non-drug therapy such as traditional Chinese exercises, acupuncture and massage, and music, etc, which could improve patients unhealthy emotions and quality of life. The recent clinical researches on TCM treatment has been increased, but the overall number of the research of this kind is limited, with problems such as small sample size, singular observing indicator, and requiring multi-center research. There still lacks related basic research and needs more attention.

Objective To determine the expression of nucleobindin 2-encoded satiety and fatinfluencing protein-1 (nesfatin-1) and interleukin (IL)-26 in the serum of patients with vitiligo,and to explore the relationship of nesfatin-1 and IL-26 with anxiety status,disease stage and distribution pattern of vitiligo lesions.Methods From March 2017 to September 2018,123 outpatients with vitiligo,as well as 30 healthy controls (control group),were enrolled from Department of Dermatology,Affiliated Hospital of Jiangsu University.Of these patients,93 rated as anxious (vitiligo with anxiety group),and 30 as nonanxious (vitiligo without anxiety group).Another 30 anxious patients with other autoimmune diseases and background diseases like hypertension and diabetes mellitus but not vitiligo (anxiety group) were enrolled from Zhenjiang Fifth People's Hospital.Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of nesfatin-1 and IL-26 in the above groups,and state-trait anxiety inventory (STAI) was used to evaluate the anxiety status.According to the vitiligo disease activity (VIDA) score,the vitiligo patients with anxiety were divided into 3 subgroups:stable stage group,active stage group and rapid progressive stage group.According to the distribution pattern of skin lesions,the vitiligo patients with anxiety were divided into 5 subgroups:localized vitiligo group,segmental vitiligo group,generalized vitiligo group,sporadic vitiligo group and acral vitiligo group.The levels of nesfatin-1 and IL-26 were compared among different stage groups and type groups.Statistical analysis was carried out using one-way analysis of variance for comparison among several groups,multi-way analysis of variance and stratification analysis for multifactor data,paired t-test for comparison before and after treatment,and Pearson correlation analysis for analyzing correlations.Results The serum level of nesfatin-1 significantly differed among the vitiligo with anxiety group,vitiligo without anxiety group,anxiety group and control group (F =10.78,P ＜ 0.001),and was significantly higher in the vitiligo with anxiety group than in the other 3 groups (P ＜ 0.001).No significant difference in the serum level of IL-26 was found among the 4 above groups (F =1.34,P =0.26).As pearson correlation analysis showed,the serum level of nesfatin-1 was positively correlated with the STAI score in the 93 vitiligo patients with anxiety (r =0.55,P ＜ 0.001).The serum level of nesfatin-1 was significantly higher in the rapid progressive stage group than in the stable stage group (P ＜ 0.05),while there was no significant difference in the IL-26 level among different stage groups (P ＞ 0.05).The generalized vitiligo patients with anxiety showed significantly increased serum level of nesfatin-1 compared with the localized vitiligo patients with anxiety (P ＜ 0.001).After 3-month treatment,the nesfatin-1 level in the 10 vitiligo patients with anxiety significantly decreased compared with that before the treatment (paired t =4.40,P =0.02),but the STAI score did not change (P ＞ 0.05).Conclusion Nesfatin-1 as an emotioninfluencing factor may participate in the occurrence of vitiligo,especially affect patients with rapid progressive vitiligo or generalized vitiligo,while IL-26 may be irrelevant to vitiligo.

Objective To evaluate the diagnostic efficacy of Kwak and ACR( 2017 ) thyroid imaging reporting and data systems ( T I‐RADS ) for thyroid nodules . Methods Cases of thyroid nodule who underwent surgery from January 2015 to M arch 2018 in 15 hospitals in Sichuan province were collected and the ultrasonographic features of thyroid nodules were retrospectively analyzed by trained senior ultrasound physicians using Kwak and ACR T I‐RADS classification methods . Totally ,12 712 thyroid nodules were observed ,7 023 thyroid nodules in 7 023 cases with complete ultrasound and surgical and pathological data were eventually enrolled in the study . T hyroid nodules with solid ,hypoechoic or very hypoechoic ,tall/wide ratio ≥ 1 , margin ill‐defined and microcalcification were classified as malignant signs of ultrasound . M alignant percentage was calculated and diagnostic tests were performed . Results ① T here was a statistical difference between the benign and malignant nodules in the two types of T I‐RADS classification ( P＜0 .01) . ② T he area under ROC curve of Kwak and ACR in the diagnosis of malignant nodules were 0 .89 and 0 .84 ,respectively . T he Youden index of Kwak and ACR were 0 .66 and 0 .57 ,respectively . ③Taking Kwak T I4B and ACR T R4 as critical points for malignancy ,the sensitivity ,specificity ,positive predictive value and negative predictive value of Kwak T I 4B were 75 .0% ,90 .9% ,83 .2% ,and 85 .9% , respectively . T he accuracy of Kwak T I4B was 84 .9% ; T he sensitivity ,specificity ,positive predictive value and negative predictive value of ACR T R4 were 88 .2% ,68 .9% ,62 .9% ,and 90 .8% ,respectively . T he accuracy of ACR T R4 was 76 .2% . T he Kappa value of Kwak TI4B and ACR T R4 was 0 .52 . T he χ2 value of Kwak T I4B and ACR T R4 was 2 174 .6 ( P ＜ 0 .01 ) . Conclusions T he diagnostic values of two T I‐RADS classification methods for thyroid malignant nodules are high . T he overall efficiency of Kwak T I‐RADS classification method is better than that of ACR TI‐RADS classification method .

With the development of modern computing technology and medical physics,radiotherapy has made great progress.The theoretical basis of radiobiology seems to lag behind the clinical application of radiotherapy,which hampers the further improvement of treatment efficacy and the optimization of treatment modality.In this paper,some emerging challenges of precision radiotherapy technology to the traditional theory of radiobiology,such as radiosensitivity,dose-response curve and survival curve,linear-quadratic model,4Rs theory,as well as the interaction between cancer and microenvironment,radiation-induced second primary cancers (RISPC),will be discussed.The interplay between precision radiotherapy and traditional radiobiology theories will be addressed with the aim to potentially solve some of the challenging problems.

Objective To evaluate the effect of latanoprost on cell proliferation of and melanogenesis in human epidermal melanocytes,and to explore its mechanism.Methods Latanoprost was added into the 254 medium to prepare latanoprost solutions at different concentrations of 10-5,10-6 and 10-7 mol/L.In vitro cultured human epidermal melanocytes were divided into 4 groups to be cultured with media containing no latanoprost (control group) or 10-5,10-6 and 10-7 mol/L latanoprost for 48 hours.Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative activity of melanocytes,dopa oxidation assay to estimate the activity of tyrosinase.Sodium hydroxide (NaOH)-lysis method was used to determine the content of melanin,and Masson-Fontana staining to observe the number and distribution of melanin granules.Westernblot analysis and real-time fluorescence-based quantitative PCR were performed to determine the protein and mRNA expression of melanogenesis-related genes including microphthalmia-associated transcription factor (MITF),tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1).Comparison among the 4 groups and multiple comparisons were done by using one-way analysis of variance and least significant difference (LSD)-t test.Results Compared with the control group,the 10-6-,10-5-mol/L latanoprost groups showed significantly increased proliferative activity of melanocytes (1.064 ± 0.172 and 1.078 ± 0.080 vs.0.784 ± 0.015;t =3.289,3.454 respectively,both P ＜ 0.05),increased activity of tyrosinase (0.510 ± 0.017 and 0.454 ± 0.009 vs.0.355 ± 0.041;t =6.139,3.939 respectively,P ＜ 0.01 or 0.05),and increased content of melanin (t =7.232,5.967,both P ＜ 0.01).However,there were no significant differences in the proliferative activity of melanocytes,activity of tyrosinase or content of melanin between the 10-7-mol/L latanoprost group and control group (all P ＞ 0.05).Masson-Fontana staining showed more and darker melanin granules on melanocyte dendrites in the 10-5-,10-6-,10-7-mol/L latanoprost groups than in the control group,and the color of melanin granules changed from light brown to black brown along with the increase in the concentration of latanoprost.The mRNA expression of MITF increased along with the increase in the concentration of latanoprost (P ＜ 0.01),and the protein expression of MITF wassignificantly higher in the 10-6,10-5-mol/L latanoprost groups than in the control group and 10-7-mol/L latanoprost group (all P ＜ 0.01).The 10-6-mol/L latanoprost group showed significantly increased mRNA and protein expression of TYR and TYRP1 compared with the control group,10-7-,10-5-mol/L latanoprost groups (all P ＜ 0.01).Conclusion Latanoprost can increase the proliferation of human epidermal melanocytes,and promote tyrosinase activity and melanogenesis likely by enhancing the mRNA and protein expression of MITF,TYR,TYRP1.