This paper summarizes Professor LU Fang's clinical experience in treating systemic lupus erythematosus （SLE） based on the differentiation and treatment of heat-toxin and blood-stasis in the collaterals. SLE is generally characterized by deficiency in origin with excess in manifestation. The core pathogenesis is heat-toxin obstructing the collaterals. During the acute active stage， the predominant pattern is blazing heat-toxin causing blood stasis， while in the chronic remitting stage， the main pattern is toxic stasis blocking the collaterals with qi and yin deficiency. Clinical treatment follows the basic principle that treat with salty-cold herbs， when heat invades internally and that assist with acrid-dispersing herbs when stasis obstructs the collaterals. The self-formulated Yimian Decoction （抑免汤） serves as the base formula and is applied in stages. During the acute active stage， it is often combined with herbs for clearing heat and detoxifying， cooling blood and resolving stasis， and unblocking the collaterals. In the chronic remitting stage， it is often combined with herbs for activating blood circulation and unblocking the collaterals， as well as tonifying qi and nourishing yin.

Objective: To explore the correlation and lag effects of environmental factors on pediatric respiratory disease visits at hospital, so as to provide scientific basis for disease prediction and optimizing clinical diagnosis and treatment. Methods: Data from 503 889 pediatric respiratory disease outpatient and emergency visits a central hospital in Minhang District of Shanghai between 2017 and 2019, along with concurrent meteorological data were collected. A distributed lag non-linear models (DLNM) was constructed to explore the specific relationship between pediatric respiratory disease consultations and various environmental factors and to quantify the cumulative lag effects of environmental factors on respiratory disease consultations. Results: Among the environmental factors, temperature, fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), nitrogen dioxide (NO 2), and sulfur dioxide (SO 2) were associated with pediatric respiratory disease visits. After adjusting for temperature, PM 2.5 and PM 10 concentrations did not show significant immediate or lag effects. The relative risk (RR) of pediatric respiratory disease visits increased with rising NO 2 concentrations. When NO 2 concentration ≥55 μg/m 3, significant immediate and lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.05, 1.13, 1.17, and 1.21( P <0.05). The RR values showed an inverted “U” shaped relationship with SO 2 concentrations. When SO 2 concentration ≥5 μg/m 3, significant lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.03 , 1.03, and 1.04 ( P <0.05). Conclusion High concentrations of NO 2 and SO 2 increase the risk of pediatric respiratory disease visits, with observable lag effects.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Proteolysis-targeting chimeras (PROTACs) have shown considerable therapeutic potential across diverse fields such as cancer, inflammation, and neurodegenerative diseases, with numerous candidates already progressing into clinical trials. More recently, their application in antiviral therapy has been rapidly gaining momentum. This review systematically outlines the mechanistic foundations and design principles of PROTACs, highlights recent advances targeting coronaviruses (including SARS-CoV-2), hepatitis C virus, human immunodeficiency virus, and influenza viruses, and critically assesses key challenges—particularly the limited diversity of E3 ligase ligands, suboptimal oral bioavailability, and the lack of integrated platforms for druggability evaluation. Looking ahead, innovations in ligand discovery, pathway modulation, delivery technologies, and conditionally activated PROTAC designs are anticipated to overcome these barriers, ushering in a new era of precise and effective antiviral therapeutics.

Objective To investigate the reversal effect and mechanism of cinobufagin(CBG)on cisplatin resist-ance in human ovarian cancer cells.Methods A2780 cell line and its cisplatin-resistant cell line A2780/DDP are common ovarian cancer cells in clinic,so these two cell lines were selected as the research objects.The cell viabil-ity was detected by cell Counting Kit-8(CCK-8)assay,and the cell proliferation ability was detected by plate clo-ning and 5-ethynyl-2′-deoxyuridine(EdU)assay.Hoechst staining was used to observe cell apoptosis.Cell scratch test and Transwell test were used to evaluate cell migration and invasion ability.Western blot and quantitative reverse transcription PCR(RT-qPCR)were used to detect the protein and mRNA expressions of phosphatidylinosi-tol 3-kinase/protein kinase(PI3K/AKT)signaling pathway and epithelial-mesenchymal transition(EMT).Re-sults Compared with A2780 cells,the drug resistance indexes of A2780/DDP cells were 5.636,5.864,5.695,respectively.After treatment of A2780/DDP cells with CBG(2,4,6 mg/ml),the reversal resistance indexes were 1.617,2.570,3.461,respectively.CBG treatment significantly increased the level of apoptosis and inhibi-ted the proliferation,migration and invasion of the cells in a concentration-dependent manner(P<0.05).Western blot results showed that compared with A2780 cells,the relative ratio of P-PI3K/PI3K and P-AKT/AKT protein levels,as well as the protein expression of N-cadherin,Vimentin,and Snail were higher in the control group(A2780/DDP)cells,while the protein expression of E-cadherin was lower(tP-PI3K/PI3K=8.115,tP-AKT/AKT=17.62,tN-cadherin=6.126,tVimentin=4.001,tSnail=17.333,tE-cadherin=4.620,P<0.01);As the dose of CBG increased,the protein expression levels of P-PI3K,P-AKT,N-cadherin,Vimentin,and Snail in drug-resistant cells de-creased,while the protein expression level of E-cadherin increased(FP-PI3K=268.5,FP-AKT=190.5,FN-cadherin=24.02,FVimentin=57.65,FSnail=87.24,FE-cadherin=135.8,P<0.05).qRT-PCR results showed that with the in-crease of CBG concentration,the mRNA expression levels of PI3K,AKT,N-cadherin,Vimentin and Snail de-creased,while the mRNA expression level of E-cadherin gradually increased(FPI3K=101.1,FAKT=558.3,FN-cadherin=86.97,FVimentin=105.9,FSnail=85.71,FE-cadherin=80.96,P<0.01).Conclusion CBG can reverse cisplatin resistance of ovarian cancer A2780/DDP cell line,and its mechanism may be related to the regulation of PI3K/AKT signaling pathway and inhibition of EMT by CBG.

【Objective】 To identify the specificity of alloantibody against high-frequency antigens in one case suffering with severe hemolytic diseases of the fetus and newborn (HDFN) and to screen for matching blood for transfusion. 【Methods】 The HDFN test and the antibody serological identification tests in the mother were performed. Several common high frequency antigens of maternal red blood cells (RBCs) were determined. IgG subtype coated on the RBCs of the newborn was determined. The phagocytic efficiency of the antibody was tested using the monocyte phagocytosis of sensitized erythrocyte by flow cytometry in vitro. Sanger sequencing of DI gene was performed in the mother, father and mother’s brother. The diluted maternal plasma was used for large scale screening of matching blood using IAT in Coomb’s gel card. 【Results】 Di(b-) phenotype was identified in the mother of the newborn and anti-Di^b (titer: 512) related HDN was detected in the newborn. IgG1 and IgG2 subtypes of anti-Di^b were detected and the rate of monocyte phagocytosis was 88.83%(74.7/84.09). The compatible blood was not detected in the maternal relatives. Subsequently, the newborn received the matching RBCs of two Di(b-) donors identified from 5 520 blood donors and discharged from the hospital. We screened out 17 Di(b-) donors out of 51 334 blood donors, indicating that the distribution frequency of Di(b-) among blood donors in Guangzhou was about 0.033% (17/51 334). 【Conclusion】 By serology and molecular biology methods, the newborn was identified with HDFN caused by anti-Di^b, and an effective large-scale screening method for Di (b -) rare blood types was established to find matching blood, which supported the establishment of rare Di(b-) blood database.

Superb microvascular imaging(SMI)is a new kind of Doppler technology,being sensitive for displaying low-velocity microvascular blood flow in muscles,tendons,synovium,nerves and reflecting microcirculation changes,able to provide imaging evidences for diagnosing musculoskeletal system diseases,monitoring processes and evaluating therapeutic effect.The research progresses of SMI applicated in musculoskeletal diseases were reviewed in this article.

OBJECTIVE To investigate the intervention effect and potential mechanism of breviscapine on hepatic fibrosis （HF） in rats based on the transforming growth factor-β（1 TGF-β1）/Smad2/extracellular signal-regulated protein kinase 1（ERK1） and Kelch-like epichlorohydrin-associated protein 1（Keap1）/nuclear factor-erythroid 2-related factor 2（Nrf2）/heme oxygenase-1（HO-1） pathways. METHODS Totally 60 rats were randomly divided into normal control group， model group， breviscapine low-dose， medium-dose and high-dose groups （5.4， 10.8， 21.6 mg/kg）， and colchicine group （positive control， 0.45 mg/kg）， with 10 rats in each group， half male and half female. Except for the normal control group， HF model of the other groups was induced by carbon tetrachloride. Subsequently， each drug group was given corresponding medicine by gavage once a day for 28 days. The liver appearance of rats in each group was observed and their liver coefficients were calculated. The levels of alanineaminotransferase （ALT） and aspartate aminotransferase （AST）in serum， those of ALT， AST， superoxide dismutase （SOD），malondialdehyde （MDA） and glutathione peroxidase （GSH- Px） in liver tissue were detected. The liver tissue inflammatory and fibrotic changes were observed. The protein and mRNA expressions of TGF-β1， Smad2， ERK1， Nrf2， Keap1 and HO-in liver tissue were detected. RESULTS Compared with the normal control group， the model group showed large areas of white nodular lesions in the liver， obvious inflammatory cell infiltration and collagen fiber deposition. The body weight， the levels of SOD and GSH-Px in liver tissue， the protein and mRNA expressions of Nrf2 and HO-1 were significantly lowered in the model group （P＜0.05）； the liver coefficient， the percentage of Masson staining positive area， ALT and AST levels of serum and liver tissue， MDA level of liver tissue， the protein and mRNA expressions of TGF-β1， Smad2， ERK1 and Keap1 were significantly increased （P＜0.05）. Compared with the model group， the liver lesions of rats in each drug group were improved， and the above quantitative indexes were generally reversed （P＜0.05）. CONCLUSIONS Breviscapine has a good intervention effect on HF rats， which may be related to inhibiting TGF-β1/Smad2/ERK1 pathway for anti-fibrosis and regulating Keap1/Nrf2/HO-1 pathway to inhibit oxidative stress.

Objective:To explore the expression of homologous recombination repair (HRR) deficiency related genes in endometrial cancer and their relationship with clinical pathological features and immune infiltration.Methods:A total of 53 patients with endometrial cancer (endometrial cancer group) who underwent surgical treatment at the Affiliated People′s Hospital of Shandong First Medical University from June 2018 to June 2020 were selected as the study subjects. Clinical data of the patients were retrospectively analyzed, and 50 healthy women who underwent physical examinations were selected as the control group. Clinical and pathological characteristics of 53 patients with endometrial cancer were collected, and real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was performed Methods The mRNA expressions of human breast cancer susceptibility gene 1 (BRCA1), tumor suppressor gene homologous loss phosphatase tensin gene (PTEN) on chromosome 10 in the peripheral blood of the subjects were detected, and the proportions of CD 4+ T cell subsets in peripheral blood monocytes were detected by flow cytometry; Pearson analysis of the correlation between peripheral blood BRCA1, PTEN mRNA expression and various subsets of CD 4+ T cell; Analysis of prognostic factors for endometrial cancer using COX risk regression model. Results:The peripheral blood BRCA1 and PTEN mRNA expression levels in patients with endometrial cancer were higher than those in the healthy control group: 2.87 ± 0.65 vs. 1.02 ± 0.13, 3.25 ± 0.74 vs. 1.01 ± 0.20, and the differences were statistically significant ( P<0.01). The proportion of peripheral blood helper T cell-2 (Th2), helper T cell-17 (Th17), regulatory T cell (Treg) and helper T cell-22 (Th22) in patients with endometrial cancer was significantly higher than that in the healthy control group: (10.72 ± 1.33)% vs. (5.43 ± 0.80)%, (9.78 ± 0.80)% vs. (3.31 ± 0.62)%, (10.81 ± 1.29)% vs. (5.74 ± 0.69)%, (6.09 ± 0.70)% vs. (3.09 ± 0.73)%, and the proportion of helper T cell-1 (Th1) was significantly lower than that in the healthy control group: (5.54 ± 0.90)% vs. (13.07 ± 2.55)%, the difference was statistically significant ( P<0.01). The peripheral blood BRCA1 and PTEN mRNA expression levels were significantly higher in patients with muscle infiltration depth ≥1/2, histological grade G 2 to G 3, lymph node metastasis, and International Federation of Obstetrics and Gynecology (FIGO) stage Ⅲ to Ⅳ than in patients with muscle infiltration depth<1/2, histological grade G 1, no lymph node metastasis, and FIGO stage Ⅰ to Ⅱ, with statistical significance ( P<0.01 or<0.05). Peripheral blood BRCA1 and PTEN mRNA were significantly positively correlated with Th2, Th17, Treg and Th22 ratios ( P<0.01), and negatively correlated with Th1 ratios ( P<0.01). COX risk regression analysis showed that histological grading, FIGO staging, depth of muscle infiltration, peripheral blood BRCA1 and PTEN mRNA expression with lymph node metastasis were all independent prognostic factors for endometrial cancer ( P<0.01 or<0.05). Conclusions:HRR deficiency related genes BRCA1 and PTEN mRNA exhibit high levels in patients with endometrial cancer, and are closely related to muscle infiltration depth, histological grading, lymph node metastasis, and FIGO staging. They can also affect the immune microenvironment of endometrial cancer patients, thereby affecting disease progression and prognosis.