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.

BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

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.

OBJECTIVE: To observe the effect and mechanism of crotonaldehyde sub-chronic exposure-induced pyroptosis in pulmonary inflammatory reaction in male rats. METHODS: Specific pathogen-free male Wistar rats were randomly divided into control group and low-, medium-and high-dose groups, with 10 rats in each group. Rats were treated with crotonaldehyde at concentrations of 0.0, 2.5, 4.5, and 8.5 mg/kg body weight by intra-gastric administration, once per day for 120 consecutive days. Rats′ body mass was recorded during exposure. After exposure, the rats were sacrificed, and the lung tissues were isolated. The relative expression of reactive oxygen species(ROS) in lung tissues was detected by fluorescent probes at the end of crotonaldehyde exposure. The fluorescent staining of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3(NLRP3) and Caspase-1 in lung tissues was observed by immunofluorescence microscope. The protein expression of NLRP3, apoptosis-associated spot-like protein(ASC), Caspase-1 precursor(pro-Caspase-1), Caspase-1, interleukin(IL)-1β and IL-18 in lung tissues was determined by Western blotting. RESULTS: At the end of exposure, the body weight gain of rats decreased with the increasing doses of crotonaldehyde(P<0.01). Among them, the body weight gain in the medium-and high-dose groups was lower than that of the control group(P<0.05). After exposure, the lung tissue of each group showed severe inflammatory change with the increasing doses of crotonaldehyde. Immunofluorescence staining showed that the expression of NLRP3 and Caspase-1 in the lung tissues of rats increased in a dose-dependent manner. The relative expression of ROS and the protein of NLRP3, ASC, pro-Caspase-1, Caspase-1, IL-1β and IL-18 in lung tissue of each group increased with the dose of crotonaldehyde(P<0.01). The above indexes of lung tissue in the medium-and high-dose groups were higher than that in the control group(P<0.05). CONCLUSION: Sub-chronic exposure to crotonaldehyde may cause pyroptosis by up-regulating ROS expression in the lung tissues of rats. The up-regulation of Caspase-1 classic dependent pathway leads to pyroptosis, thereby causing inflammatory responses in the lungs.

Objective To explore the effects of vascular risk factors on cognitive function among the elderly in community. Methods A cross-sectional study was conducted in 1 269 elderly people ( aged 65 and over) who were randomly selected from three communities. Through face-to-face interview, cognitive function was assessed by mini-mental state examination(MMSE),and blood samples were collected for labo-ratory examination. Logistic regression analysis was used to analyze the vascular risk factors affecting cogni-tive function. Results Age (( 73. 1 ± 6. 6), ( 71. 3 ± 4. 9),t=4. 603,P<0. 05),education level ( χ2=12. 727,P<0. 05),hypertension (χ2=9. 106,P<0. 05) and LDL-C (χ2=5. 157,P<0. 05) were significantly different in the elderly with or without mild cognitive impairment(MCI). After controlling age,gender and ed-ucation,the logistic regression analysis showed that hypertension(β=0. 378,P=0. 006,OR(95%CI)=1. 44 (1. 10-1. 91)),systolic blood pressure ≥140 mmHg( β=0. 350,P=0. 011,OR( 95% CI)= 1. 42( 1. 08-1. 86),1 mmHg=0. 133 kPa),and high LDL-C( β=0. 355,P=0. 014,OR(95%CI)=1. 43( 1. 08-1. 89)) were the risk factors of MCI in the elderly in the community. Hypertension alone or high LDL-C (β=0. 365, P=0. 029,OR(95%CI)=1. 44(1. 04-2. 00)) alone was risk factor for mild cognitive impairment in the eld-erly in the community. The risk of mild cognitive impairment in the elderly with hypertension and high LDL- C was 2. 00 times higher than that in the healthy elderly ( β=0. 696,P<0. 05,OR( 95%CI)= 2. 00( 1. 36-2. 97)). Conclusion Mild cognitive impairment in the elderly is closely related to hypertension and elevat-ed LDL-C levels. Multiple vascular risk factors can further increase the risk of cognitive impairment.

Objective: To explore the effects of vascular risk factors on cognitive function among the elderly in community. Methods: A cross-sectional study was conducted in 1 269 elderly people (aged 65 and over) who were randomly selected from three communities.Through face-to-face interview, cognitive function was assessed by mini-mental state examination(MMSE), and blood samples were collected for laboratory examination.Logistic regression analysis was used to analyze the vascular risk factors affecting cognitive function. Results: Age ((73.1±6.6), (71.3±4.9), t=4.603, P<0.05), education level (χ²=12.727, P<0.05), hypertension (χ²=9.106, P<0.05) and LDL-C (χ²=5.157, P<0.05) were significantly different in the elderly with or without mild cognitive impairment(MCI). After controlling age, gender and education, the logistic regression analysis showed that hypertension(β=0.378, P=0.006, OR(95%CI)=1.44(1.10-1.91)), systolic blood pressure ≥140 mmHg(β=0.350, P=0.011, OR(95%CI)=1.42(1.08-1.86), 1 mmHg=0.133 kPa), and high LDL-C(β=0.355, P=0.014, OR(95%CI)=1.43(1.08-1.89)) were the risk factors of MCI in the elderly in the community.Hypertension alone or high LDL-C (β=0.365, P=0.029, OR(95%CI)=1.44(1.04-2.00)) alone was risk factor for mild cognitive impairment in the elderly in the community.The risk of mild cognitive impairment in the elderly with hypertension and high LDL-C was 2.00 times higher than that in the healthy elderly (β=0.696, P<0.05, OR(95%CI)=2.00(1.36-2.97)). Conclusion Mild cognitive impairment in the elderly is closely related to hypertension and elevated LDL-C levels.Multiple vascular risk factors can further increase the risk of cognitive impairment.

Objective: To put forward the suggestion of the occupational contact limit of tributyl phosphate in the air of the workplace. Methods: Data of production and usage, workers' basic information, occupational history, and physical examinations were collected, and the environmental and individual levels of exposure were monitored using fixed-point and individual sampling. The results of the questionnaire and health examination were statistically analyzed using exact probability method of Fisher in the workers exposed to tributyl phosphate and the control group. Results: The results showed that tributyl phosphate was widely distributed in the workplace of production and using enterprises, and the concentration of tributyl phosphate in packaging area was highest at 2.47 mg/m³, and in feeder nose was highest at 2.13 mg/m³. The discomfort symptoms were classified and results showed that tributyl phosphate exposure group of 136 people, all symptoms of 128 people, accounting for 94.44% of the total, the remaining 5.56% of the staff report had psychiatric symptoms or lethargy and irritability skin itching, the control group had no symptoms. There is or not discomfort symptoms in the tributyl phosphate exposure group and the control group was compared with the exact probability of Fisher, and the difference was statistically significant (P<0.05) . The results of healthy physical examination of workers exposed to tributyl phosphate and control group were statistically analyzed by the exact probability method of Fisher. The results showed that there was no significant difference in the results of routine internal medical examination, nervous system examination, skin examination, five senses examination, blood routine, urine routine, lung ventilation, and X ray chest fluoroscopy between the tributyl phosphate exposure group and the control group (P<0.05) . Conclusion The workplace permissible time-weighted tributyl phosphate and short-term exposure limit concentrations in China were set at 2.5 mg/m³ and 5 mg/m³, respectively.