[Progress on microneedle drug delivery systems for the treatment of corneal diseases].

Corneal diseases are prevalent eye conditions in China, and the lack of effective treatment in the short term can lead to blindness. However, delivering drugs to the cornea safely and effectively poses a significant challenge due to the presence of ocular barriers and clearance mechanisms. Conventional drug delivery methods exhibit low bioavailability, making it difficult to achieve therapeutic effects. Microneedles, with their ability to penetrate ocular surface barriers effectively, offer a low-invasive and highly promising drug delivery technology. This article introduces the main delivery barriers on the ocular surface, classifies microneedles, and highlights the latest developments in the treatment of corneal diseases. Finally, the potential challenges of applying microneedle delivery systems to the ocular surface are analyzed, aiming to provide insights for the clinical application of microneedles in corneal diseases.

Clinical effectiveness of semaglutide on weight loss, body composition, and muscle strength in Chinese adults.

OBJECTIVE: The aim of this study was to investigate the clinical effectiveness of semaglutide on weight loss, body composition and muscle strength in the Chinese population with obesity. PATIENTS AND METHODS: Data were retrospectively analyzed for participants prescribed semaglutide in 2021 and 2022 from a Chinese weight management clinic. Changes in weight, body composition, biochemical indicators, calf circumference and handgrip strength were collected. Body fat and skeletal muscle were also measured using the bioelectrical impedance analysis. Paired t-test was used to compare the values after 6 months of treatment with the baseline values. RESULTS: A total of 53 obese patients received 24 weeks of lifestyle intervention plus semaglutide treatment. 10 patients who failed to adhere to the follow-up were excluded, and 43 patients were studied. The average baseline body mass index (BMI) was 33.0 kg/m2, and the average body weight was 90.0 kg. After 6 months of treatment, the patient's weight was significantly reduced by 9.9 ± 3.9 kg (p < 0.001), and the weight loss percentage was 11.2 ± 4.5% (p< 0.001). The proportion of patients with weight loss ≥ 5% and ≥ 10% was 93% and 54%, respectively. Fasting blood glucose, fasting insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index, blood uric acid and blood lipid levels also decreased after treatment. Body composition analysis showed that the loss of skeletal muscle mass was 1.4 ± 1.3 kg (p < 0.001), which was significantly less than the loss of fat mass of 5.6 ± 3.7 kg (p < 0.001). By percentage, the fat mass loss was 15.6 ± 10.1%, and the muscle mass loss was 4.8 ± 4.4% (p < 0.001). The visceral fat area was significantly reduced by 24.4 ± 17.7 cm (p < 0.001). There was no significant change in skeletal muscle index (8.1 ± 1.0 kg/m2 at baseline and 7.9 ± 1.0 kg/m2 at 24 weeks). The calf circumference (42.6 ± 3.6 cm at baseline, 41.2 ± 3.8 cm at 24 weeks) and grip strength (33.3 ± 9.5 kg at baseline, 32.3 ± 9.0 kg at 24 weeks) did not decrease significantly. The main adverse reactions were mild gastrointestinal dysfunction (nausea, diarrhea and vomiting), without ketoacidosis. CONCLUSIONS: In a real-world setting, semaglutide can reduce the weight and fat of obese patients while effectively maintaining muscle mass and muscle strength.

Precision Measurement of Reactor Antineutrino Oscillation at Kilometer-Scale Baselines by Daya Bay.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.

[Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients].

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

[Influence of dietary pattern on human immunity].

Objective: To systematically review the relationship between dietary patterns and human immunity and health. Methods: Chinese and English search terms, including "dietary pattern", "dietary structure", "nutrients", "food", "protein", "fat", "vitamins", "dietary fiber", "immunity", "inflammatory", "inflammation", "oxidative stress", were searched for relevant articles in PubMed, Web of Science, Wanfang and National Knowledge Infrastructure (CNKI) database from the collection start date to January 10, 2020. Results: A total of 1 Chinese article and 22 English articles were included, including 9 cross-sectional studies, 7 intervention studies, 6 cohort studies and 1 nested case-control study. Common evaluation methods for dietary patterns included dietary inflammatory index (DII), inflammatory score of the diet (ISD), empirical dietary inflammatory pattern (EDIP), dietary compliance score, and healthy eating index. There were 13 studies on Mediterranean dietary patterns and healthy dietary patterns with higher intake of vegetables, fruits, bean products, fish and dairy products in the included articles. The Mediterranean diet can reduce the levels of inflammatory markers such as CRP, IL-6, Hcy, WBC, and fibrinogen, as well as the levels of metabolic indicators such as vascular endothelial growth factor and endothelial function score, improve chronic inflammatory diseases and reduce the risk of chronic diseases. The higher the healthy diet score was, the lower the level of pro-inflammatory factors was. Even if the dietary recommendation was not met, the healthier the diet was, the lower the level of inflammatory factors was. Western dietary patterns were positively correlated with CRP, IL-6, E-selectin, sICAM-1, sVCAM-1 and other inflammatory factors, and can increase the incidence of type 2 diabetes and the risk of cardiovascular disease. However, one study did not found the relationship between them and hs-CRP. Conclusions: Dietary patterns are closely related to human immune function. Different dietary patterns have different inflammatory potentials according to the characteristics of food intake, which can directly or indirectly affect immune function.

[Effect of nutrition on human inflammatory and oxidative stress markers].

Objective: To systematically review the effects of nutrients, food and diet patterns on markers of inflammation and oxidative stress. Methods: Nutrients, nutrition, food, diet, dietary structure, dietary patterns, protein, fat, vitamin, dietary fiber, inflammatory, inflammation, oxidative stress, immunity were used as search terms, and systematic retrieval of the literature in Wanfang Database, National Knowledge Infrastructure (CNKI), PubMed, Web of Science was carried out from the establishment of the database to January 10, 2020, and a systematic review of the literature meeting the requirements was conducted. Results: A total of 3 Chinese and 46 English articles were included. Literature showed that ß-carotene, vitamin C, vitamin D, polyunsaturated fatty acids, some amino acids, dietary fiber, isoflavones, choline, betaine and resveratrol and other nutrients can reduce plasma inflammatory factors or oxidative stress marker levels, and nutrients such as cholesterol and trans fatty acids can increase their levels. Foods such as fish, lean meat, fruits, soybeans, cruciferous vegetables and nuts can reduce plasma inflammatory factors or oxidative stress marker levels, while foods such as milk and sugary beverages can increase plasma inflammatory factors or oxidative stress markers. Mediterranean dietary patterns and other healthy dietary patterns can reduce plasma levels of inflammatory factors or oxidative stress markers, while Western dietary patterns can increase their levels. Conclusion: Nutrients, food and dietary patterns can influence levels of plasma inflammatory factors or oxidative stress markers.

[Research methods to influence of nutrition on human immunity].

Objective: To systematically review the advances in population research methods of dietary nutrition and human immunity. Methods: Related studies on the relationship between dietary nutrition and human immunity were searched in PubMed, Web of Science, Wanfang and China National Knowledge Infrastructure (CNKI) databases from the start date to January 10, 2020. A systematic review of the literatures that met the requirements was carried out. Results: Totally 114 articles were included, including 4 Chinese articles and 110 English articles. There were 22 cross-sectional studies, 16 case-control studies, 41 cohort studies and 35 intervention studies, respectively. The research methods showed a trend of diversification over time. In recent years, the derivative types of case-control studies such as nested case-control studies and case cohort studies received attention. Research factors gradually shifted from a single nutrient or dietary ingredient to food and dietary patterns. The protective effect of nutrition on gene damage, the effect on altering gene expression, and the regulatory effect of genetic polymorphism on the sensitivity of nutrients and inflammatory markers became research hotspots. Conclusion: The epidemiologic research methods of dietary nutrition and human immune function are constantly improving and developing, which play an important role in fully demonstrating the relationship between nutrition and human immune function.

[Influence of nutrients on human immunity].

Objective: To systematically review the studies on impact of macronutrients and micronutrients on human's immunity including cell-meditated immunity and humoral immunity as well as disease outcome. Methods: The database searched included Wan Fang Data, China National Knowledge Infrastructure, PubMed and Web of Science. "Nutrients" , "food" , "diet structure" , "diet pattern" , "protein" , "fat" , "vitamin" , "mineral" etc. were searched in Chinese and English for nutrition related terms, and "inflammation" , "inflammatory" , "oxidative stress" , "immune" , "immunity" etc. were searched for immunity related terms in Chinese and English respectively for published articles till Jan. 10th, 2020. Results: A total of 53 articles including 18 Chinese articles and 35 English articles were included in this review. Studies mainly focused on the relationship between nutrients such as iron, zinc, vitamin A, vitamin D, vitamin E and fatty acids and immunity. In a summary, insufficiency or deficiency of nutrients would impact immunity of humans which was mostly reflected in changes of CD3(+), CD4(+), CD4(+)/CD8(+), IgA and IgG levels. Furthermore, nutrient intake level or serum level was associated with disease outcomes such as prevalence, occurring risk or severity of symptoms. Interventions studies on n-3 polyunsaturated fatty acid (n-3 PUFA), zinc and vitamin A confirmed the positive effects of such nutrients on immunity and disease outcome. Conclusions: The intake level or serum level of nutrients is associated with cell-meditated immunity and humoral immunity. Optimal status of nutrients plays an important role in effectively strengthening immune system and disease defense of humans.

[Selection of the cutoff value on tuberculin skin test in diagnosing tuberculosis infection: a population-based cross-sectional study in Eastern China].

Objective: To confirm the cutoff induration diameter of tuberculin skin test (TST) so as to decrease the false positive of the TST. Methods: Fasting blood glucose test, TST and Quanti FERON-TB (QFT) Gold In-Tube test were administered to recruit participants at the baseline stage. QFT was used as the gold standard to determine the cutoff of the TST test. Results: Overall, 5 405 participants were enrolled in this study, of whom 1 104 (20.4%) were QFT positive. Among all the 5 405 participants that without stratification, diagnostic value reached the highest when the induration diameter was 10.25 mm with sensitivity and specificity as 0.731 and 0.727, respectively. When the participants were divided into groups as nondiabetics, confirmed diabetics, undiagnosed diabetics, the sensitivities and specificities appeared as 0.701, 0.837, 0.824 and 0.805, 0.821, 0.778 with induration diameters as 11.25 mm, 10.25 mm and 11.25 mm, respectively. Conclusions: Findings of this study confirmed that the specificity of tuberculin test could be significantly improved by using 10-12 mm as the cutoff value for diagnosing the latent tuberculosis infection.

Clinical practice guideline for image-guided multimode tumour ablation therapy in hepatic malignant tumours.

Multimode tumour ablation therapy is a treatment method that combines cryoablation with radiofrequency ablation, guided by medical imaging technology and based on precise planning, targeting, monitoring, and control of the thermal energy delivered, with the aim of achieving a whole-body antitumour immune response to malignant tumours. To develop standardized criteria for the application of multimode tumour ablation therapy to malignant hepatic tumours, to facilitate actualization of the criteria in various hospitals, and to ensure therapeutic efficacy and safety, the Society of Interventional Therapy of the Chinese Anti-Cancer Association and the Solid Tumor Theranostics Committee of the Shanghai Anti-Cancer Association assembled experts who specialize in oncology to discuss this treatment method and to arrive at a clinical practice consensus guideline for the indications, contraindications, and techniques of multimode tumour ablation therapy for malignant hepatic tumours.

MicroRNA-363-3p/p21(Cip1/Waf1) axis is regulated by HIF-2α in mediating stemness of melanoma cells.

Melanoma is a malignant tumor. The acquisition of stemness of melanoma cells aggravates the malignant transformation, which can be regulated by microRNAs (miRNAs, miR). MiR-363-3p is a key tumor-related miRNA, but its role in stemness and melanoma cells is still unknown. Presently, miR-363-3p, induced by hypoxia inducible factor (HIF)-2α, played a positive role in the stemness of melanoma cells. The levels of miR-363-3p and HIF-2α were upregulated in melanoma cell lines. Overexpression of HIF-2α significantly increased the levels of miR-363-3p. However, both HIF-2α knockdown and miR-363-3p inhibition inhibited the levels of the stemness markers (CD133, CD271, Jarid1B, and Nanog). Furthermore, the levels of miR-363-3p and HIF-2α were upregulated in fluorescence activated cell sorting (FACS)-sorted CD271high/+ cells. Whereas miR-363-3p depletion reduced the proportion and the spheroidization of the CD271high/+ cells, decreased the levels of CD133, CD271, Jarid1B and Nanog with restrained proliferative activity of CD271high/+ cells. Additionally, miR-363-3p was confirmed a key downstream of HIF-2α. Intriguingly, cyclin-dependent kinase inhibitor 1A [CDKN1A, p21(Cip1/Waf1)], a key inhibitor of S-phase DNA synthesis and cell cycle progression, was confirmed a target gene of miR-363-3p by luciferase reporter gene assay. The protein levels of CD133, CD271, Jarid1B and Nanog were upregulated with enhanced proliferative activity of CD271high/+ cells by inhibition of p21 in melanoma cells. In conclusion, miR-363-3p is induced by HIF-2α to promote the stemness of melanoma cells via inhibiting p21. The present study provides novel insights that HIF-2α/miR-363-3p/p21 signaling may be a potential target of research and therapy of melanoma.

[The combination of percutaneous iohexol-ethanol injection with radiofrequency ablation for the treatment of primary liver cancer in high-risk locations].

Objective: To investigate the safety and efficacy of radiofrequency ablation (RFA) with percutaneous iohexol-ethanol injection (PIEI), compared with RFA plus transcatheter arterial chemoembolization (TACE) for patients with primary liver cancer(PLC)in high-risk locations. Methods: From January 2012 to December 2014, 54 patients with PLC in high-risk locations were enrolled. They were divided into Group A (RFA combined with PIEI) and Group B (RFA plus TACE). The efficacy and adverse events were assessed. Results: 54 patients had 74 lesions in high-risk locations. There were 26 cases with 40 lesions in Group A, and 28 cases with 34 lesions in Group B. The complete ablation rate of Group A was significantly higher than that of Group B (92.5% vs 70.6%, P=0.014). The two-year local tumor progressionrateand two-year overall survival rate were similar between these two groups (Group A 20.0% vs Group B 38.2%, P=0.083; 90.3% vs 84.3%, P=0.523). Furthermore, the surgery-related severe adverse events of Group A (7.1%, one case of liver abscess and one case ofhematobilia) were more common than that of Group B (0%, P=0.491). No significant differences were found in common adverse events including fever, pain, elevation of aminotransferase and bilirubin. Conclusions: Compared with RFA plus TACE, RFA plus PIEI resulted inbetter complete ablation rate in patients with primary liver cancer in high risk locations. Prospective, randomized, controlled trials are warranted for further evaluation.

[Retrospective analysis of outcomes of selectively or spontaneously reduced multiple pregnancies out of 6 917 in vitro fertilization-embryo transfer pregnancy cycles].

Objective: To analyze the effects of fetal reduction in early pregnancy on obstetric and neonatal outcomes of spontaneously or selectively reduced multiple pregnancies produced by in vitro fertilization-embryo transfer (IVF-ET). Methods: Retrospective study of 6 917 clinical pregnancies from IVF-ET cycles, including 754 multiple pregnancies divided into two groups according to the remaining fetus number: reduced singleton group (n=599) and reduced twin group (n=155); and maternal and neonatal outcomes of two groups were compared to primary singleton group (n=3 589) and primary twin group (n=2 574). Results: The rate of pregnancy complication [9.85%(59/599) versus 6.21%(223/3 589)], preterm birth [19.37%(116/599) versus 10.73%(385/3 589)], low birth weight [9.71%(56/577) versus 4.57% (152/3 324)], perinatal death [0.69%(4/577) versus 0.12%(4/3 324)] and malformation [2.95%(17/577) versus 1.02%(34/3 324)] in reduced singleton group were significantly higher than those in primary singleton group (all P<0.01). There were no significant differences between reduced twin group and primary twin group (all P>0.05). In reduced singleton group, birth defect rate was 2.95%, which was higher than those of the other three groups (P<0.05), in this group spontaneous pregnancy reduction accounted for 89.3% (535/599). Conclusions: (1) The rate of pregnancy complication, preterm birth, low birth weight, perinatal death and malformation in reduced singleton group are still higher than primary singletons, suggesting embryo reduction only is a compensated method in multiple pregnancies. Limiting the number of embryos transferred is the essential solution. (2) The rate of birth defect in spontaneous pregnancy reduction group is higher, so prenatal examination should be reinforced in this group.

Identification of cervical cancer markers using cDNA subtraction approach.

PURPOSE OF INVESTIGATION: Cervical cancer markers are not well known for accurate detection of the disease. MATERIALS AND METHODS: In the present study, cervical cancer samples were collected from the 42 patients in the Department of Surgery and Medicine of Weifang People's Hospital and Medical College, Shandong, China. The cDNA subtraction approach was performed to find out the specific transcripts, which are responsible for cervical cancer. The specific differentially expressed transcripts were identified by Basic Local Alignment Search Tool (BLAST) analysis and the results were validated by immunohistochemistry. RESULTS: Following differentially expressed specific transcripts, such as ID-1, Hif 1a, and the Y-box were usefully employed as a marker to accurately detect cervical cancer. CONCLUSION. The identified markers are promising in the accurate detection of cervical cancer in terms of its molecular basis and management of the disease.

Biomarkers of peritoneal fluid in endometriosis identified by surface-enhanced laser desorption/ionization time-of-flight.

OBJECTIVES: This work aims to detect the peritoneal fluid proteomic patterns in endometriosis patients, build diagnostic models, and evaluate its clinical significance. STUDY DESIGN: The authors used SELDI-TOF-MS protein chip array technology to detect biomarkers of peritoneal fluid in endometriosis patients. Fourteen endometriosis patients and 16 persons without endometriosis as control group were tested. RESULTS: Four potential biomarkers (4428m/z, 6891m/z, 13766m/z, and 6427m/z) were found. CONCLUSIONS: This method showed great potential in screening better biomarkers for endometriosis.

Docetaxel-cisplatin might be superior to docetaxel-capecitabine in the first-line treatment of metastatic triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) may be more sensitive to platinum. This study was to compare platinum-based regimen with nonplatinum regimen in the first-line treatment of advanced TNBC. PATIENTS AND METHODS: Eligible metastatic TNBC (mTNBC) women without prior treatment for advanced disease were randomized (1 : 1) to receive either docetaxel-cisplatin (TP) or docetaxel -capecitabine (TX) q3w for up to 6 cycles, until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) and the secondary end points included progression-free survival (PFS) and overall survival (OS). In total 53 patients were enrolled. RESULTS: The median follow-up was 24 months. ORR was higher in the TP group than in the TX group (63.0% versus 15.4%, P = 0.001). PFS was more than doubled (10.9 months versus 4.8 months, P < 0.001) and median OS was also greatly improved (32.8 months versus 21.5 months, P = 0.027). Toxic effects were not different except G3/4 vomiting and G2/3 hand-foot syndrome. CONCLUSIONS: This study suggested that cisplatin-based chemotherapy was superior to capecitabine-based regimen in the first-line treatment of mTNBC, as measured by ORR, PFS and OS. Further large-scale study should be warranted. These results are not sufficient to change clinical practice.

Cross-talk between endothelial cells and tumor via delta-like ligand 4/Notch/PTEN signaling inhibits lung cancer growth.

Lung cancer is a leading cause of cancer death in many countries. Notch signaling has been demonstrated to frequently participate in the process of lung carcinogenesis. Delta-like ligand 4 (Dll4) is a vascular-specific ligand of Notch, and has a critical role in the angiogenesis of numerous cancers. However, the role of Dll4 in the cross-talk between endothelial cells (ECs) and tumor cells remains obscure. Herein, our study revealed that Dll4-expressing ECs (EC-Dll4) significantly suppressed the proliferation of neighboring non-small cell lung cancer (NSCLC) cells and attenuated the growth of NSCLC xenograft in nude mice. On the contrary, silencing endothelial Dll4 by its specific interference RNA reversed these effects of Dll4 on NSCLC cell proliferation and tumor formation. Furthermore, activation of Notch1, but not Notch2 or Notch3, was enhanced in NSCLC cells cultured with EC-Dll4, as well as in xenografts induced by a mixture of NSCLC cells and EC-Dll4. Interference of Notch1 significantly attenuated Dll4-mediated suppression of NSCLC cell proliferations, indicating that Dll4/Notch1 signaling negatively modulates the NSCLC growth. Moreover, PTEN expression in NSCLC cells was increased by EC-Dll4 or rhDll4 (recombinant human-Dll4 protein), and the induction was impaired by Notch1 interference suggesting that Dll4 could upregulate PTEN expression by Notch1. Taken together, we conclude that the cross-talk between ECs and NSCLC cells by Dll4/Notch1/PTEN signaling pathway inhibits the growth of NSCLC.