ObjectiveTo investigate the protective effect of Huayu Jiedu prescription against PC12 cell damage induced by a combination of neutrophil extracellular traps （NETs） and oxygen-glucose deprivation （OGD）. MethodsFirst， dimethyl sulfoxide （DMSO） was used to induce the differentiation of the human promyelocytic leukemia cell line （HL-60） into neutrophil-like cells （dHL-60）， and cell differentiation was assessed through Giemsa staining and flow cytometry. Next， phorbol myristate （PMA） was used to induce the formation of NETs in dHL-60 cells. The formation of NETs was assessed via SYTOX Green staining， and NETs were extracted by low-speed centrifugation. Finally， the NETs prepared through the conditioned medium were combined with OGD to induce a high-differentiation PC12 neuronal cell damage model through the co-culture method. This model was treated with the Huayu Jiedu prescription-containing serum. Cells were randomly allocated into a normal control group， a model （NETs + OGD） group， a traditional Chinese medicine （NETs + OGD + 5% Huayu Jiedu prescription-containing serum） group， and a NETosis inhibitor （100 mg·L^-1 DNase I + NETs + OGD） group. The cell counting kit-8 （CCK-8） assay was used to evaluate cell viability and screen the optimal intervention concentrations of NETs and Huayu Jiedu Formula-containing serum， as well as the optimal intervention time for OGD. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of myeloperoxidase-DNA complexes （MPO-DNA）， citrullinated histone H3 （CitH3）， and neutrophil elastase （NE）. Western blot was employed to quantify the protein levels of CitH3 and cleaved Caspase-3. Terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） staining and flow cytometry were employed to assess neuronal apoptosis. ResultsCompared with those in the normal control group， cells in the model group successfully differentiated into dHL60 cells after DMSO induction. Wright-Giemsa staining revealed that the cells in the model group had disappeared nucleoli， distinct reniform and lobulated changes of nuclei， highly condensed chromatin， and the cytoplasm containing pale purple fine granules. Flow cytometry showed that the mean fluorescence intensity （MFI） of CD11b in the model group was enhanced （P<0.01）. Compared with those in the normal control group， dHL60 cells in the model group successfully generated NETs after PMA induction. SYTOX Green staining revealed loss of cell membrane integrity， with chromatin released from the cytoplasm to form abundant extracellular， cloud-like fibrillar structures， and a marked increase in fluorescence intensity （P<0.01）. Through the CCK-8 assay for assessing the viability of highly differentiated PC12 cells， the optimal concentration for NETs was determined as 1 000 ng·L^-1， the optimal concentration of Huayu Jiedu formula-containing serum as 5%， and the optimal duration for OGD as 2 h. Compared with the normal control group， the model group showed elevated levels of MPO-DNA， CitH3， and NE （P<0.01） and upregulated protein levels of CitH3 and cleaved Caspase-3 （P<0.01）. Furthermore， TUNEL staining revealed an increased proportion of apoptotic cells （P<0.01） and flow cytometry showed an increased apoptosis rate （P<0.01） in the model group. Compared with the model group， the Huayu Jiedu formula-containing serum group and the NETosis inhibitor group exhibited declined levels of MPO-DNA， CitH3， and NE （P<0.05，P<0.01） and downregulated protein levels of CitH3 and cleaved Caspase-3 （P<0.01）. In addition， TUNEL staining showed a decrease in the proportion of apoptotic cells （P<0.01）， and flow cytometry revealed a decrease in the apoptosis rate （P<0.01）. ConclusionHuayu Jiedu prescription may exert a protective effect against ischemic neuronal damage by inhibiting NET formation or alleviating NET-induced neurotoxicity

ObjectiveTo investigate the protective effect of Huayu Jiedu prescription against PC12 cell damage induced by a combination of neutrophil extracellular traps （NETs） and oxygen-glucose deprivation （OGD）. MethodsFirst， dimethyl sulfoxide （DMSO） was used to induce the differentiation of the human promyelocytic leukemia cell line （HL-60） into neutrophil-like cells （dHL-60）， and cell differentiation was assessed through Giemsa staining and flow cytometry. Next， phorbol myristate （PMA） was used to induce the formation of NETs in dHL-60 cells. The formation of NETs was assessed via SYTOX Green staining， and NETs were extracted by low-speed centrifugation. Finally， the NETs prepared through the conditioned medium were combined with OGD to induce a high-differentiation PC12 neuronal cell damage model through the co-culture method. This model was treated with the Huayu Jiedu prescription-containing serum. Cells were randomly allocated into a normal control group， a model （NETs + OGD） group， a traditional Chinese medicine （NETs + OGD + 5% Huayu Jiedu prescription-containing serum） group， and a NETosis inhibitor （100 mg·L^-1 DNase I + NETs + OGD） group. The cell counting kit-8 （CCK-8） assay was used to evaluate cell viability and screen the optimal intervention concentrations of NETs and Huayu Jiedu Formula-containing serum， as well as the optimal intervention time for OGD. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the levels of myeloperoxidase-DNA complexes （MPO-DNA）， citrullinated histone H3 （CitH3）， and neutrophil elastase （NE）. Western blot was employed to quantify the protein levels of CitH3 and cleaved Caspase-3. Terminal-deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） staining and flow cytometry were employed to assess neuronal apoptosis. ResultsCompared with those in the normal control group， cells in the model group successfully differentiated into dHL60 cells after DMSO induction. Wright-Giemsa staining revealed that the cells in the model group had disappeared nucleoli， distinct reniform and lobulated changes of nuclei， highly condensed chromatin， and the cytoplasm containing pale purple fine granules. Flow cytometry showed that the mean fluorescence intensity （MFI） of CD11b in the model group was enhanced （P<0.01）. Compared with those in the normal control group， dHL60 cells in the model group successfully generated NETs after PMA induction. SYTOX Green staining revealed loss of cell membrane integrity， with chromatin released from the cytoplasm to form abundant extracellular， cloud-like fibrillar structures， and a marked increase in fluorescence intensity （P<0.01）. Through the CCK-8 assay for assessing the viability of highly differentiated PC12 cells， the optimal concentration for NETs was determined as 1 000 ng·L^-1， the optimal concentration of Huayu Jiedu formula-containing serum as 5%， and the optimal duration for OGD as 2 h. Compared with the normal control group， the model group showed elevated levels of MPO-DNA， CitH3， and NE （P<0.01） and upregulated protein levels of CitH3 and cleaved Caspase-3 （P<0.01）. Furthermore， TUNEL staining revealed an increased proportion of apoptotic cells （P<0.01） and flow cytometry showed an increased apoptosis rate （P<0.01） in the model group. Compared with the model group， the Huayu Jiedu formula-containing serum group and the NETosis inhibitor group exhibited declined levels of MPO-DNA， CitH3， and NE （P<0.05，P<0.01） and downregulated protein levels of CitH3 and cleaved Caspase-3 （P<0.01）. In addition， TUNEL staining showed a decrease in the proportion of apoptotic cells （P<0.01）， and flow cytometry revealed a decrease in the apoptosis rate （P<0.01）. ConclusionHuayu Jiedu prescription may exert a protective effect against ischemic neuronal damage by inhibiting NET formation or alleviating NET-induced neurotoxicity

Objective To investigate the relationship between primary pulmonary mucinous adenocarcinoma (PPMA) mass type and pneumonia type and their difference in malignant degree, and to analyze the role of clinical manifestations and CT features in the diagnosis of this disease. Methods The clinical data of PPMA patients admitted in the First Affiliated Hospital of Xiamen University from May 2011 to March 2022 were retrospectively analyzed. According to CT features, they were divided into a mass type group and a pneumonia type group. The clinical manifestations, CT features and the degree of malignancy between the two groups were analyzed and compared. Results A total of 57 PPMA patients were enrolled. There were 17 males and 40 females, with an average age of (53.82±10.65) years, and 28 (49%) patients had reversed hato-like sign. There were 42 patients in the mass type group and 15 patients in the pneumonia type group. PPMA often occurs in both lower lungs, with clinical manifestations mainly of coughing and expectorating white mucoid sputum. There were statistical differences between the two groups in the maximum diameter of tumor (P<0.001), boundary condition (P<0.001) and pleural indentation sign (P=0.019). There was no statistical difference between the two groups in Ki-67 index (P>0.05). Conclusion There is no statistical difference in the degree of malignancy between the two types of PPMA. Considering their clinical manifestations and differences in imaging features, it is supported that the pneumonia type is just a progression of the mass type. CT can present various manifestations, among which the reversed hato-like sign is expected to become an important imaging feature. Combined with a high proportion of solid components, pleural indentation sign, and vacuole sign, reversed hato-like sign can play a significant role in the diagnosis of PPMA.

Objective:This study investigated the dynamic expression of lipocalin-2(LCN2)and its receptor,brain-type organic cation transporter protein(BOCT),in spinal cords of hSOD1G93A transgenic mice during disease pro-gression,providing potential targets for early anti-inflammatory therapy for ALS.Methods:Utilizing hSOD1G93A trans-genic mice and their wild-type littermates(WT)as animal models,this investigation examined the expression of LCN2 and BOCT at four distinct disease stages:pre-symptomatic stage(60 d),early-symptomatic stage(95 d),symptomatic stage(108 d),and late-symptomatic stage(122 d).Spinal cords were harvested,then RT-qPCR,Western blot,and immunofluorescence double-labeling techniques were employed to assess alteration expressions of LCN2 and BOCT.Ad-ditionally,BV2 cells transfected with the pcDNA3.1-G93A-SOD1 overexpression plasmid served as an in vitro hSOD1G93A BV2 microglial model.After stimulated with LPS for 24 hours,LCN2 mRNA and protein expression in hSOD1G93A BV2 microglial cells and its culture medium were measured by RT-qPCR and ELISA respectively,while BOCT expression was measured by Western blot.Results:Compared with WT mice littermates,increased expression of LCN2 mRNA was detected in the spinal cords of hSOD1G93A transgenic mice at 108 and 122 d.No significant differences were observed in LCN2 or BOCT protein expression in the spinal cords of hSOD1G93A transgenic mice from 60 to 122 d.Double-immunofluorescence labeling revealed co-localization of LCN2 and BOCT with the microglial marker Iba-1 in the ventral horn of lumbar spinal cord of hSOD1G93A transgenic mice from 95 to 122 d.In hSOD1G93A BV2 microglial model,LPS stimulation led to a significantly increased LCN2 mRNA expression and protein secretion.Conversely,there was no significant change in BOCT protein expression after LPS stimulation.Conclusion:Our findings suggest that during ALS progression,there is an enhanced expression and release of LCN2 from activated microglia,potentially exacerbating neuroinflammation and neuronal degeneration.

Objective:To explore the clinical efficacy of percutaneous balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) based on the double difference (DID) model.Methods:A retrospective case - control study method was adopted to analyze the general data of 130 patients with trigeminal neuralgia (TN) who were treated in the Department of Neurosurgery of Hebei General Hospital from January 2022 to October 2023. Among them, 49 were males and 81 were females. The age was (53.28±11.67) years, ranging from 25 to 80 years old. According to different treatment methods, the patients were divided into an experimental group ( n=63) and a control group ( n=67). Patients in the experimental group were given percutaneous balloon compression (PBC) treatment, while those in the control group were treated with conservative drug therapy. Propensity score matching method was used for 1∶1 matching. After matching, there were 52 cases in each group. The general data of the two groups were compared. The visual analogue scale (VAS), 36-item short form health survey (SF-36) score, Hamilton depression rating scale (HAMD) score, Hamilton anxiety rating scale (HAMA) score, 5-hydroxytryptamine, neuropeptide P, inflammatory factor interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) before and after treatment, as well as the clinical efficacy of the two groups of patients were comparatively analyzed. Meanwhile, the incidence of postoperative complications in the two groups was compared. The generalized estimating equation (GEE) model was used to analyze the influencing factors of clinical efficacy, and the difference-in-differences (DID) model was used to evaluate the efficacy before and after treatment. Measurement data conforming to the normal distribution were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups; the chi- square test was used for comparison between count data. Results:After treatment, the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level in the experimental group were (2.98±0.83) points, (75.56±1.18) points, (7.2±0.83) points, (7.15±0.85) points, (76.34±5.47) ng/mL, (50.95±11.01) pg/mL, (29.45±7.08) ng/L, and (21.18±3.55) ng/L respectively. In the control group, there were (3.63±0.95) points, (73.23±1.13) points, (7.98±0.80) points, (8.04±0.84) points, (186.31±11.61) ng/mL, (86.52±13.32) pg/mL, (34.47±6.58) ng/L, and (26.36±5.80) ng/L, respectively. The differences between the two groups were statistically significant ( P<0.05).The cure rate and the total incidence of postoperative complications in the experimental group were 55.77% and 13.46% respectively, while in the control group, they were 40.38% and 30.77% respectively. The differences between the two groups were statistically significant ( P<0.05).The results of the GEE model analysis showed that age, course of disease, VAS, SF-36 score, HAMA score, HAMD score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, TNF-α level, treatment method, and the long - diameter ratio of FO significantly affected the clinical efficacy of patients ( P<0.05).The results of the DID model showed that the experimental group was superior to the control group in improving the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level( P<0.05). Conclusion:PBC can significantly improve the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine, neuropeptide P, IL-1, TNF-α, and incidence of complications in patients with TN. It can also improve the psychological status and quality of life of patients.

Objective:To investigate the predictive value of transabdominal uterine electromyography for pre-term labor after tocolysis in women with threatened preterm labor.Methods:A total of 48 pregnant women at 28-34 weeks of gestation diagnosed with threatened preterm labor and admitted to The Fourth Affiliated Hospital of Soo-chow University from January to September 2023 were included.According to the response to tocolysis and whether the pregnancy was prolonged for at least 48 h,women were divided into two groups:non-preterm birth within 48 h(n=35)and preterm birth within 48 h(n=13).Uterine electromyography parameters and difference were compared before and after tocolytic therapy in two groups.Univariate Logistic regression was performed to predict the related factors of preterm birth within 48 h after the using of tocolysis in pregnant women with threat-ened preterm birth by uterine electromyography,and receiver operating characteristic(ROC)curve was per-formed to evaluate their performance.Results:Compared to before treatment with tocolysis,after therapy,in the non-preterm birth within 48 h group,significant reductions in contraction frequency,area,duration and amplitude were observed(P<0.05).In the preterm birth within 48 h group,only contraction frequency decreased significant-ly(P<0.05).Univariate Logistic regression indicated that contraction frequency,contraction duration,and contrac-tion area were predictive factors for premature birth within 48 h after tocolysis(P<0.05).When the duration of u-terine contractions lasting for 104.55 s or more the sensitivity and specificity of predicting premature birth within 48 h are 92.3％and 68.6％,respectively.Conclusions:Uterine electromyography may predict the premature birth within 48 h after tocolytic treatment in preterm labor,which may provide reference for subsequent corticosteroid therapy or transfer of high-risk pregnant patients.

Olfactory disorders are a common symptom in patients with chronic rhinosinusitis, and their diagnosis and treatment have garnered extensive attention from both patients and doctors. Currently, there are various evaluation and treatment methods for olfactory dysfunction; however, choosing a simpler and more accurate assessment, as well as an effective treatment, remains a clinical challenge. In this article, we review the assessment and treatment methods commonly used in clinical practice in recent years to provide better support for the diagnosis and treatment of olfactory disorders.
Humans ; Olfaction Disorders/etiology* ; Sinusitis/complications* ; Chronic Disease ; Rhinitis/complications* ; Rhinosinusitis

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.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.