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 compare the efficacy and safety of red light and daylight photodynamic therapy in the treatment of facial common acne.Methods:From March 2019 to November 2019, 52 patients with facial common acne who received 5-aminolevulinic acid photodynamic therapy in the Department of Dermatology, Chongqing Hospital of Traditional Chinese Medicine were enrolled, including 34 males and 18 females, aged 18-35 years, with an average age of 23.2 years. A 5% concentration of 5-aminolevulinic acid was applied to the entire face, with the right side of the face being exposed to red light for 20 minutes and the left side to daylight for 2 hours. The treatment was administered once a week for a total of 4 sessions. After the treatment, the acne remission, adverse reactions, and patient satisfaction on both sides of the face were compared.Results:Compared with before treatment, the number of inflammatory and non-inflammatory lesions on both sides of the face in the enrolled patients decreased, and there was no significant difference in the clearance rate of skin lesions between the two sides [53.7% (28/52) vs 59.1% (31/52), χ 2=0.89, P>0.05]. The overall effective rate on the red light side was 88.5% (46/52), and 82.7% (43/52) on the daylight side, with no significant difference between the two (χ 2=0.38, P>0.05). In terms of adverse reactions, mild erythema was common, and it was less on the daylight side than on the red light side [34.6% (18/52) vs 19.2% (10/52), χ 2=5.98, P<0.05]. During the treatment period, the pain score on the daylight side decreased compared to the red light side [(7.6±2.3) vs (4.1±1.3), t=13.10, P<0.001]. Overall satisfaction with the daylight side was reported in 49 cases (94.2%), and with the red light side in 37 cases (71.2%), with the daylight side being higher than the red light side, and the difference was statistically significant (χ 2=9.60, P<0.05). Conclusion:Daylight photodynamic therapy is as effective as red light photodynamic therapy for common acne, but it produces fewer adverse reactions and higher patient satisfaction.

Objective To observe the impact of ultrasonic image quality on the consistency of artificial intelligence(Al)assisted diagnosis system and manual measurements of biological indicators of developmental dysplasia of hip(DDH).Methods Hip ultrasonic data of 75 DDH and 345 non-DDH children were retrospectively analyzed,and the quality of ultrasonic images were subjectively scored.An evaluation model of ultrasonic image quality was constructed based on 140 ultrasonic images acquired from 140 cases(group A,containing 25 DDH and 115 non-DDH)using entropy weighting method,the weight of anatomic structures and impact factors related to DDH were obtained.The comprehensive image quality scores of other ultrasonic images acquired from 280 cases(group B,including 50 DDH and 230 non-DDH)were calculated,and the images in group B were classified into grade A,B and C in descending order.The consistency of AI and manual measurements of DDH biological indicators in group B was assessed.Results The weight of each anatomic structure and impact factors of DDH obtained with the model were as follows:The lower edge of iliac branch＞ilium＞glenoid labrum＞bony margin＞femoral head＞motion artifacts.In group B,grade A was observed in 67(9 DDH and 58 non-DDH),grade B was found in 160(26 DDH and 134 non-DDH),while grade C was noticed in 53(15 DDH and 38 non DDH)images.Except for β,femoral head coverage(FHC)and femoral head length diameter,the consistencies between AI and manual measurements of other indicators of DDH were grade A＞B＞C.In group B,AI and manual measurements were more consistent in DDH than in non-DDH cases.Conclusion Ultrasonic image quality affected the consistency between AI and manual measurements of biological indicators of DDH.When image quality was not good enough,further attention should be paid to measurement of FHC and sizes of femoral head.

【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.

BackgroundCombination of antipsychotic drugs and modified electroconvulsive therapy （MECT） is currently a commonly used method for treating schizophrenia， but its efficacy varies among different patient groups. ObjectiveTo explore the therapeutic effects of MECT on schizophrenia patients living in different urban versus rural environments， so as to provide references for the selection of treatment plans based on patients' residence. MethodsA total of 587 patients hospitalized at Luzhou Mental Health Center， Zigong Mental Health Center and Yibin Fourth People's Hospital from May 2018 to August 2022， who met the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） ，were included in the study. Patients were divided into two groups： medication-only group （n=106） and MECT combined with medication group （n=481）. In MECT combined with medication group， 24 rural patients residing in urban areas were excluded， leaving the remaining patients divided into urban group （n=103） and rural group （n=354） based on their place of residence. Positive and Negative Syndrome Scale （PANSS） was used to assess the severity of symptoms. Clinical efficacy was evaluated using PANSS score reduction rate， and covariance analysis was used to compare the therapeutic effects of different patients. ResultsThe differences of reduction rate of PANSS total score， positive symptom scale score and negative symptom scale score as well as treatment effectiveness rate between MECT combined with medication group and medication-only group were statistically significant （F=11.149， 12.111， 31.725， χ²=14.010， P<0.01）. Statistically significant differences were also observed in reduction rate of PANSS total score and positive symptom subscale score as well as treatment effectiveness rate between urban and rural patients in MECT combined with medication group （F=3.946， 4.523， χ²=4.033， P<0.05）. ConclusionThe efficacy of MECT combined with medication may be superior to medication alone in the treatment of schizophrenia， and the combined therapy may be more effective in urban patients than that in rural patients， with potentially more pronounced improvements in positive symptoms.

[Abstract] [Objective] To further identify the RhD phenotype and RHD genotype in the individual who have RhD negative phenotype in the primary screening, and to analyze the effect of c. 801+2T>G mutation on RhD phenotype by minigene splicing assay. [Methods] The serologic test was performed for RhD phenotype identification and absorption-elution test was performed by using monoclonal anti-D. Sanger sequencing was used to analyze the sequence of RHD genes and the newly identified splicing site mutations of RHD genes were used to construct pSplicePOLR2G micro gene expression plasmids. By using an in vitro micro gene splicing system, the mRNA splicing results were detected and analyzed using agarose and capillary electrophoresis to predict their impact on RhD phenotype. [Results] The serological test results showed that the patient's blood type was RhD-negative, but the anti-D absorption-elution test was positive, indicating a Del phenotype. The rare genotype RHD^*(1227A/801+2G) was identified in this individual. The c. 801+2T>G was a novel mutation at 5'-splice site of intron 5. The minigene splicing assay showed that c. 801+2T>G resulted in a complete skipping of RHD exon 5 in the mature transcript, forming a transcript without exon 5. [Conclusion] An individual carrying a novel mutation c. 801+2T>G in the RHD gene was found to exhibit a Del phenotype, but also carry the Asian Del allele c. 1227G>A. It was speculated that the c. 801+2T>G mutation caused RhD negative or Del phenotype based on the results of minigene splicing assay in vitro.