ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Background: Automated insulin delivery (AID) systems studies are upsurging, half of which were published in the last 5 years. We aimed to evaluate the efficacy and safety of AID systems in patients with type 1 diabetes mellitus (T1DM). Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until August 31, 2023. Randomized clinical trials that compared AID systems with other insulin-based treatments in patients with T1DM were considered eligible. Studies characteristics and glycemic metrics was extracted by three researchers independently. Results: Sixty-five trials (3,623 patients) were included. The percentage of time in range (TIR) was 11.74% (95% confidence interval [CI], 9.37 to 14.12; P<0.001) higher with AID systems compared with control treatments. Patients on AID systems had more pronounced improvement of time below range when diabetes duration was more than 20 years (–1.80% vs. –0.86%, P=0.031) and baseline glycosylated hemoglobin lower than 7.5% (–1.93% vs. –0.87%, P=0.033). Dual-hormone full closed-loop systems revealed a greater improvement in TIR compared with hybrid closed-loop systems (–19.64% vs. –10.87%). Notably, glycemia risk index (GRI) (–3.74; 95% CI, –6.34 to –1.14; P<0.01) was also improved with AID therapy. Conclusion AID systems showed significant advantages compared to other insulin-based treatments in improving glucose control represented by TIR and GRI in patients with T1DM, with more favorable effect in euglycemia by dual-hormone full closedloop systems as well as less hypoglycemia for patients who are within target for glycemic control and have longer diabetes duration.

Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

Objective:To explore the trajectory of depressive symptoms and its related factors in rural women in Yunnan from first trimester of pregnancy to 42 days after childbirth.Methods:The longitudinal study design was used,and 213 pregnant women from a rural county of Yunnan were selected.The Edinburgh Postnatal Depression Scale(EPDS),Generalized Anxiety Disorder(GAD-7),and Perceived Social Support Scale(PSSS)were used to surveyed in their first trimester of pregnancy,and followed up in their second and third trimesters of pregnancy and 42 days after childbirth.The analysis was conducted using latent growth curve models,latent class growth models,and multivariate logistic regression models.Results:The results of the latent growth curve models showed a gradual decrease in perinatal depressive symptom scores over time.The latent class growth models revealed three distinct la-tent classes:persistent high depression score group(1.41％),stable low depression score group(91.08％),and fluctuating depression symptoms group(7.51％).Multivariate logistic regression indicated that women with lower education levels(OR=4.04),anxiety symptoms(OR=4.12),and lower social support(OR=3.12)were more likely to be classified into the persistent high depression score group and fluctuating depression symptoms group.Conclusions:The trajectories of perinatal depression symptoms among rural women in Yunnan could be di-vided into three heterogeneous subgroups.Women with low education levels,anxiety symptoms,and lack of social support are more likely to be detected with perinatal depression symptoms.

Objective:To investigate the feasibility and optimal expansion width of replacing the left anterior descending coronary artery (LADCA) with the region of heart sparing (RHS) to reduce cardiac radiation dose during breast cancer radiotherapy.Methods:Retrospective analysis was conducted on data from 88 patients with left-sided breast cancer who underwent radiotherapy at 2 centers: Nanfang Hospital of Southern Medical University (50 cases for the training set, 15 cases for the internal test set) and Ganzhou Hospital of Nanfang Hospital (23 cases for the external test set) from March 2022 to January 2024. All patients had left-sided invasive ductal carcinoma with axillary lymph node metastasis, and had undergone modified radical mastectomy and chemotherapy. Based on simulation CT images, 2 radiation oncologists delineated the LADCA and 8 RHSs. The RHSs were delineated by expanding the LADCA contour by 0.5 cm increments, totaling 8 expansions. The RHS widths were defined as 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 cm. The nnU-Net model was trained for 3D automatic segmentation of the LADCA and RHSs. Model performance was evaluated using the Dice similarity coefficient (DSC), relative volume error (RVE), sensitivity, specificity, and 95% Hausdorff distance (HD95). Additionally, the minimum, maximum, and average relative dose variations (RDV) as well as V5% and V20% indicators were calculated for the LADCA and each RHS. Correlation analysis was performed using the least squares regression, with the slope and coefficient of determination ( R2) employed to evaluate the accuracy of the model fitting, the relationship between the LADCA and RHS, and the degree of their correlation, thereby assessing the substitutive effect of the RHS for the LADCA. Results:The DSC for the LADCA was 0.415, while the DSCs for RHS widths of 0.5 cm and 4.0 cm were 0.718 and 0.835, respectively. Overall, the automatic segmentation performance improved with increasing RHS width. The DSC, RVE, sensitivity, specificity, and HD95 for the external test set were largely consistent with those of the internal test set, demonstrating the model's good robustness across different datasets. All RDVmin values were negative, while RDVmax and RDVmean showed a positive correlation with RHS width. RDVmean increased from 39.01% to 75.89% as the RHS width increased. In the correlation analysis, the slopes for RHS widths of 1.5 cm and 2.0 cm were 0.95 and 1.05, respectively, with R2 values and coefficients of variation of 0.79 and 0.73, and 21.11% and 24.03%, respectively. Conclusions:The automatic segmentation model trained on nnU-Net can accurately segment RHSs. Based on geometric and dosimetric indicators, a 1.5 cm-wide RHS is the most suitable substitute for the LADCA, effectively limiting the radiation dose to the LADCA without compromising target dose coverage.

Fibrinogen-like protein 1(FGL1)is a novel hepatic factor and a member of the fibrinogen family.FGL1 has diverse and complex functions and is involved in the regulation of multiple biological processes.FGL1 has an important role in the study of metabolic diseases,but further studies are needed to reveal its underlying mechanisms and the feasibility of clinical applications.This review is to summarize the role of FGL1 in the development and progression of DM,obesity,metabolic associated fatty liver disease and polycystic ovarian syndrome.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

Objective To explore the efficacy of 4R technology combined with prone five-direction cer-vical muscle strength training for neck type cervical spondylosis.Methods A total of 112 patients with neck and shoulder pain who visited the Affiliated Shapingba Hospital of Chongqing University and the Shapingba District Traditional Chinese Medicine Hospital in Chongqing from January to November 2024 were selected as research subjects.They were randomly assigned using a random number table method into an observation group and a control group,with 56 patients in each group.The observation group received 4R technology com-bined with prone five-direction cervical muscle strength training,while the control group received conventional rehabilitation treatment.Both interventions lasted for 4 weeks.Differences in Visual Analogue Scale(VAS)scores,Neck Disability Index(NDI)scores,and cervical range of motion in flexion,extension,lateral bending,and rota-tion were assessed before treatment and at 1 and 6 months after treatment for both groups.Results At 1 and 6 months of treatment,VAS scores in both groups decreased compared to before treatment,with the observation group lower than the control group,and the difference was statistically significant(P<0.05).At 1 and 6 months of treatment,NDI scores in both groups decreased compared to before treatment,with the observation group lower than the control group,and the difference was statistically significant(P<0.05).At 1 and 6 months of treatment,cervical flexion,cervical extension,and cervical lateral flexion in both groups increased compared to before treatment,and cervical rotation in the observation group increased compared to before treatment.Cervical extension and cervical rotation in the observation group were greater than those in the con-trol group,and only at 6 months of treatment was cervical lateral flexion in the observation group greater than in the control group,with all differences statistically significant(P<0.05).Conclusion The 4R technology combined with prone five-direction cervical muscle strength training can effectively improve cervical-type cer-vical spondylosis.