Diabetic kidney disease （DKD） is one of the main causes of chronic kidney disease. Both traditional Chinese medicine （TCM） and western medicine have their own advantages in the prevention and treatment of DKD， but there are also many difficulties. By analysis of the difficulties faced by TCM and western medicine in the differentiation and treatment of DKD， based on the theory of "miniature masses in the renal collaterals"， combined with long-term clinical practice， "internal heat leading to mass" is proposed as the core pathogenesis of DKD. Therefore， a trinity model of "disease-syndrome-symptom" for differentiation and treatment of DKD based on the core pathogenesis has been proposed. This model highlights the status of the core pathogenesis of "internal heat leading to mass" in DKD， and conducts a three-dimensional identification from the perspectives of disease， syndrome and symptom， so as to inspire clinical practice.

The " liver disease affecting to the spleen" theory first appeared in Nanjing and was further elaborated in Jingui Yaolue. This theory encapsulates the traditional Chinese medicine principles of the " unity of the five viscera" and the " preventive treatment of disease" . The theory emphasizes that the spleen is the pivotal point where depression may progress from a functional disorder to an organic disease. The liver governs the emotions and qi flow, whereas the spleen is responsible for qi, blood, and body. In the early stages of the disease, emotional disorders and qi flow disorders primarily affect the liver, manifesting as depression or low mood. As the condition progresses, the liver (Wood) overacts on the spleen (Earth), disrupting liver and spleen functions and causing qi and blood disharmony. This stage is marked by fatigue and psychomotor retardation. Prolonged illness depletes qi and blood, eventually involving all five viscera, disrupting the harmony of the five spirits, and affecting both body and spirit. At this advanced phase, intense emotional distress or agitation often arises, accompanied by a heightened risk of suicide. The disease progression follows a dynamic " qi-blood-spirit" pattern, in which depression begins in the liver, characterized by qi stagnation, then affects the spleen, involving blood disharmony. In later stages, the disease eventually affects all viscera, with profound effects on both physical and mental health. Treatment strategies should align with the disease stage. Early intervention should focus on regulating the flow of qi, treating the liver, and strengthening the spleen. In the middle stages, qi and blood should be harmonized while promoting the harmonized functions of the liver and spleen. In the later stages, treatment should harmonize the five viscera to restore balance between body and spirit. Guided by this theory, integrating modern medical understanding of the progression of depression from emotional to somatic symptoms and adopting a stage-based approach to treatment in clinical practice can yield effective therapeutic outcomes for managing depression and related disorders.

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

ObjectiveTo investigate the status and dietary intake risk of pesticide residues in fruits and vegetables sold in Wenzhou, Zhejiang Province from 2020 to 2023, so as to provide a scientific basis for the regulation and management of pesticide in the future. MethodsIn accordance with the requirements and methods specified in the “National Food Contamination and Hazardous Factor Risk Monitoring Work Manual” and the current corresponding national food inspection standards for various foods, a total of 807 samples of vegetables and fruits from various counties and districts of Wenzhou City were collected for testing and analysis. Eventually, 23 types of pesticides with a detection rate greater than 5% and those exceeding the standard were selected for dietary intake risk assessment. ResultsFrom 2020 to 2023, the overall detection rate of pesticide residues in fruits and vegetables monitored in Wenzhou was 71.62%, with an overall exceedance rate of 5.27%. From the results of the monitoring of pesticide residues in fruits and vegetables, fresh legume vegetables had the highest detection rate of 90.00%. Among the six major categories of pesticides monitored, fungicides in vegetables and fruits had the highest detection rates of 68.18% and 85.03%, respectively. The highest exceedance rate in vegetables was organophosphorus pesticides, accounting for 2.85%, while in fruits, neonicotinoid pesticides had the highest exceedance rate of 3.21%. From the perspective of sampling time, the peak detection rate of pesticide residues in fruits and vegetables in Wenzhou occurred in June and October. The index of food safety (IFS) of the 23 pesticides with a detection rate higher than 5% ranged from 0.000 7 to 0.694 2 based on the 95% monitoring value of pesticide residues, which were all less than 1. Calculated at maximum content, the IFS values of dithiocarbamate (calculated by CS₂), chlorothalonil and propiconazole were all greater than 1, indicating that the maximum detection values of the three pesticides exceeded the acceptable safety risk. The risk level of acute dietary intake of the 23 pesticides ranged from 1.26% to 52.65%. ConclusionThe overall situation of pesticide residues in fruits and vegetables sold in Wenzhou from 2020 to 2023 is favourable, but the exceedance rate of pesticide in some fruits and vegetables is high. Special attention should be paid to the pesticide residues of fungicides, neonicotinoid insecticides and organophosphorus pesticides in fresh legume vegetables, bulb vegetables and some fruits sold in Wenzhou, such as acetamiprid in bayberry and cowpea, dimethomorph in strawberry, chlorpyrifos in leek, etc., and monitoring of pesticide residues in food need to be strengthened.

Pancreatic cancer is characterized by nerve invasion and a high mortality rate， and its pathological process depends on the complex interaction network between tumor and the nervous system. Based on the concept of “pancreatic cancer neuroecology”， this article analyzes the mechanism of action of peripheral motor nerve， sensory nerve， and central nerve in tumorigenesis， pain regulation， and cachexia formation and emphasizes the synergistic regulatory role of immune cells， Schwann cells， and extracellular matrix in the microenvironment of perineural invasion. At the same time， this article further elaborates on the metabolic interaction and chemotaxis between neuraxis and tumor， the effect on promoting chemotherapy resistance， and the dynamic relationship between neuroplasticity and tumor adaptability. In clinical practice， this article summarizes the key value of perineural invasion in prognostic evaluation， preoperative evaluation， and the selection of surgical strategy. In addition， this article reviews the basic research advances in the biomarkers and potential targets associated with perineural invasion in pancreatic cancer and points out the limitations of current model and transformation research. In the future， systematically analyzing the nerve-tumor-immune network and targeting its key nodes may provide multi-dimensional strategies and new breakthroughs for the precise intervention of pancreatic cancer， the reversal of drug resistance， and the relief of symptoms.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules （DHBY， the prescription for consolidating body resistance） and Fuling Yunhua granules （FLYH， the prescription for treating symptoms） on spontaneous type 2 diabetes mellitus （T2DM） in mice. MethodsAccording to the fasting blood glucose （FBG） level， 12-week-old db/db mice were randomized into six groups： model， DHBY （18.02 g·kg^-1）， FLYH （14.80 g·kg^-1）， sequential administration 1 （SEQ-1， DHBY 18.02 g·kg^-1+FLYH 14.80 g·kg^-1）， sequential administration 2 （SEQ-2， FLYH 14.80 g·kg^-1+DHBY 18.02 g·kg^-1）， and dapagliflozin （Dapa， 1.3 mg·kg^-1）. The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal， the retinal thickness， FBG， hemoglobin A1c （HbA1c）， and insulin were determined， and histopathological changes of the pancreas， liver， kidney， and retina were observed by hematoxylin-eosin （HE） staining. ResultsCompared with the model group， SEQ-1 for 4 weeks lowered the FBG level （P<0.05）， raised the insulin level， decreased the triglyceride （TG） level （P<0.05）， increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels （P<0.05）， rose the insulin level， increased the retinal thickness and the number of optic ganglion cells （P<0.05）， and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal， Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However， the levels of FBG and HbA1c in the SEQ-2 group remained decreasing （P<0.05）. ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy， and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover， SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

Objective To analyze the monitoring status of occupational hazard factors in key industry workplaces in a city of the Pearl River Delta area from 2019 to 2023. Methods A total of 1 548 enterprises in 12 key industries of the city were selected as the research subjects using the judgmental sampling method. Their monitoring data for dust, chemical factors, and noise, along with the occupational health management status of the enterprises were analyzed. Results Among the 1 548 enterprises, large and medium-sized enterprises accounted for 2.7% and 13.4%, while small and micro enterprises accounted for 83.9%. A total of 474 enterprises exceeded the national limit in the detection of occupational hazard factors, with an exceedance rate of 30.6%. The rates of workers exposed to occupational hazard factors, dust, chemical factors, and noise were 29.4%, 6.9%, 21.0%, and 13.0%, respectively, all showing a downward trend year by year (all P<0.05). The training rates for occupational health among enterprise managers, responsible persons, and workers were 84.1%, 84.2%, and 91.2%, respectively. The detection rates for abnormal occupational health examinations among workers exposed to dust, chemical factors, and noise were 0.2%, 0.3%, and 0.5%, respectively. The setting rates of warning signs and warning instructions among enterprises for dust, chemical toxins, and noise were 87.3%, 91.1%, and 89.5%, respectively. The setting rates for dust, toxic chemical, and noise control facilities were 72.4%, 75.4%, and 46.0%, with effectiveness rates of 70.5%, 56.6%, and 55.2%, respectively. The distribution rates of personal protective dust masks, gas masks, and noise earplugs/earmuffs were 91.9%, 83.8%, and 86.4%, with wearing rates of 80.8%, 70.5%, and 76.4%, respectively. The detection rates of exceeding national limits for dust, chemical factors, and noise in the work site of occupational hazard factors were15.2%, 1.0%, and 21.6%, respectively. The detection rates of exceeding national limits for dust, chemical factors, and noise in the workplace of occupational hazard factors were 2.4%, 2.5%, and 12.3%, respectively. The exceedance rate for noise in work site showed an upward trend year by year (P<0.01). Conclusion Occupational disease prevention and control work in the key industries of this city needs strengthening. It is essential to further enhance the regular monitoring and preventive measures of occupational hazard factors in enterprises, improve protective measures, strengthen the use of personal protective equipment, and enhance occupational health training and supervision, to effectively reduce the risk of occupational diseases and protect workers' occupational health rights.

Objective: To evaluate the application of blood conservation measures in obstetric patients with different red blood cell transfusion volumes and to assess the impact of different transfusion volumes on postpartum outcomes. Methods: A retrospective investigation was conducted on 448 obstetric patients who received blood transfusions at the Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2016 to December 2022. Patients were divided into four groups (1-2 units group, 3-4 units group, 5-6 units group, and >6 units group) based on the volumes of red blood cells (RBCs) transfused during and within 7 days after delivery. The maternal physiological indicators, pre- and postpartum laboratory test indicators, obstetric complications, application of blood conservation measures, use of blood products, and postpartum outcomes were reviewed. The clinical characteristics, application of blood conservation measures, and their impact on postpartum outcomes were compared among different transfusion groups. Results: There were statistically significant differences in the multivariate logistic analysis of history of previous cesarean section (OR=1.781), eclampsia/pre-eclampsia/(OR=1.972) and postpartum blood loss>1 000 mL（OR=1.699）(P<0.05) among different transfusion groups. In terms of blood conservation measures, the more RBCs transfused, the higher the rate of mothers receiving blood conservation measures such as balloon occlusion, arterial ligation, autologous blood transfusion with a cell saver, and hysterectomy. With the increase in the volume of RBCs transfusion, the demand for fresh frozen plasma（FFP）, cryoprecipitate, and platelet transfusions also increased. The hospitalization days for the four groups of parturients were 6.0 (4.0-9.0), 7.5 (5.0-14.8), 7.0 (4.5-13.0) and 11.0 (9.0-20.5), respectively (P<0.05) and the rates of ICU transfer were 2.0% (5/250), 9.4% (12/128),18.2% (6/33) and 51.4% (19/37), respectively (P<0.05). Both increased significantly with the increase in the volume of RBCs transfusion, and the differences between groups were statistically significant. Conclusion: Parturients who received higher volume of RBCs had multiple risks factors for bleeding before childbirth, had higher postpartum blood loss, and had a higher rate of application of various blood conservation measures. In addition, an increase in the volume of RBCs transfusion may have adverse effects on postpartum recovery.