ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

OBJECTIVE: Since Omicron will likely persist, this trial evaluates the safety and efficacy of Shufeng Jiedu Granule (SFJDG) for mild Omicron infection, aims at finding new therapies especially for home-treated patients. METHODS: This randomized, double-blind, placebo-controlled, multi-center phase III trial involves 844 patients, divided into a treatment group (422) and control group (422). Participants will receive SFJDG or placebo for 7 d (1.2 g/bag, 2 bags, 3 times/d). Hospital evaluations will be done on days 1 and 8, with telephone assessments on days 3 and 5. Follow-up continues on days 10 and 14. Diary cards will track symptom scores and safety data. The primary outcome is the time to sustained clinical recovery from corona virus disease 2019 (COVID-19) symptoms. An interim analysis will occur after 70 % of patients complete follow-up, with Type I error correction (α1 = 0.015) at interim analysis based on O'Brien-Fleming-type cumulative error spending function. RESULTS: This phase III trial evaluates the efficacy and safety of SFJDG for mild COVID-19, focusing on real-world applicability for home-managed patients. The study's randomized, double-blind, placebo-controlled design ensures methodological rigor, while its comprehensive outcome measures address both symptom recovery and treatment safety. By emphasizing symptom resolution and recovery time, the trial aligns with the clinical priorities for managing mild cases of COVID-19. The findings could offer valuable insights into SFJDG's role in improving patient outcomes and addressing gaps left by existing antiviral therapies, particularly in symptom management. CONCLUSION The global risk assessment remains high due to the ongoing virulence of SARS-CoV-2 Omicron sub-lineages. This Phase III study adopts a robust methodology to investigate SFJDG as a treatment for mild COVID-19 as well as it's effectiveness and safety. Furthermore, this study aim to provide sufficient scientific evidence for the market registration of SFJDG especially for home-treated patients. If successful, SFJDG could be a meaningful addition to therapeutic options for mild infections, supporting public health strategies in managing the ongoing impact of SARS-CoV-2.

BACKGROUND:Studies have shown that hesperetin exerts protective effects on chondrocytes through a variety of mechanisms or signaling pathways,but the protective mechanisms have not been fully elucidated. OBJECTIVE:To investigate the effect of hesperetin on lipopolysaccharide-induced inflammatory degeneration of chondrocytes. METHODS:Knee joint chondrocytes from suckling Sprague-Dawley rats were isolated and cultured in vitro,and identified by Safranine O staining.The cytotoxicity of hesperetin on chondrocytes was determined by the MTT assay to ensure the optimal concentration of hesperetin.Chondrocytes were randomly divided into three groups,including the control group,model group,and experimental group.The cellular model of osteoarthritis was established in the latter two groups by simulating chondrocytes with lipopolysaccharide.Chondrocytes in the experimental group was then intervened with hesperetin for 24 hours.Calcein-AM/EthD-I staining was used to detect cell viability.Immunohistochemical staining was performed to determine the expression of type Ⅱ collagen in chondrocytes.Intracellular reactive oxygen species level was detected by a reactive oxygen species detection kit.Total glutathione level was detected by ELISA.Real-time fluorescent PCR was employed to detect the expression of interleukin 1β,interleukin 6,tumor necrosis factor α and type Ⅱ collagen. RESULTS AND CONCLUSION:Safranine O staining results showed that the cells extracted were chondrocytes.Cytotoxicity test results showed 0.5 μmol/L hesperetin had the most significant effect on chondrocyte vitality.Compared with the control group,the model group showed a decrease in chondrocyte proliferation ability,an increase in reactive oxygen species levels,a decrease in total glutathione levels,an increase in type Ⅱ collagen degradation,an increase in the levels of interleukin 1β,interleukin 6,and tumor necrosis factor α,and a decrease in the expression of type Ⅱ collagen(P＜0.05).Compared with the model group,in the experimental group,the proliferation ability of chondrocytes increased,reactive oxygen species levels decreased,total glutathione levels increased,and type Ⅱ collagen degradation decreased,levels of interleukin 1β,interleukin 6,and tumor necrosis factor α downregulated,and the expression of type Ⅱ collagen upregulated(P＜0.05).To conclude,hesperetin has a protective effect on lipopolysaccharide-induced inflammatory degeneration of osteoarthritic chondrocytes,and the mechanism may be associated with inhibition of reactive oxygen species-mediated oxidative stress.

Objective To observe the regulatory effects of Yitangkang on neuroinflammation and polarization of microglia and astrocytes in db/db mice;To explore the its mechanism in the treatment of cognitive impairment in diabetes.Methods Totally 32 db/db mice were randomly divided into model group,liraglutide group,and Yitangkang low-and high-dosage group.Another C57BL/6 mice were taken as blank group,with 8 mice in each group.Yitangkang low-and high-dosage group were given Yitangkang Decoction 15,30 g/kg respectively,the liraglutide group was intraperitoneally injected with liraglutide 200 μg/kg,the blank group and model group were given the same volume of distilled water by gavage,for 5 weeks.FJC staining was used to observe the damage of hippocampal neurons,ELISA was used to detect the content of IL-6 and IL-1β in hippocampal tissue,immunohistochemistry was used to detect the expressions of IL-6,IL-1β,Iba1 and GFAP in hippocampal tissue,the expressions of CD86,CD206,C3,S100A10,NLRP3,Iba1 and GFAP were detected by immunofluorescence,the protein expressions of CD86,CD206,C3,S100A10 and NLRP3 in hippocampal tissue were detected by Western blot.Results Compared with the blank group,the FJC positive cells in the model group significantly increased,and the contents of IL-6 and IL-1β significantly increased,the expressions of Iba1,CD86,GFAP and C3 significantly increased,CD206 and S100A10 expressions significantly decreased,NLRP3 protein expression and co-expression with Iba1 and GFAP significantly increased,with statistical significance(P<0.05,P<0.01).Compared with the model group,the FJC positive cells in hippocampal tissue of liraglutide group and Yitangkang low-and high-dosage group significantly decreased,the contents of IL-6 and IL-1β significantly decreased,the expressions of Iba1,CD86,GFAP and C3 significantly decreased,the expressions of CD206 and S100A10 significantly increased,the expression of NLRP3 protein and co-expression with Iba1 and GFAP were significantly decreased,the differences were statistically significant(P<0.05,P<0.01)except for CD206 in Yitangkang low-dosage group.Conclusion Yitangkang can effectively regulate the expression of NLRP3 in db/db mice,promote the transformation of microglia/astrocytes from M1/A1 type to M2/A2 type,inhibit the inflammatory response,and exert neuroprotective effects.

Objective:Pediatric chronic sinusitis （CRS） is a common disease within the field of otolaryngology-head and neck surgery. Due to the immaturity of sinus development and immune competence in children, its etiology and pathophysiology are complex, and its clinical features and outcomes differ significantly from those in adult patients. Currently, there are issues in the diagnosis and treatment of pediatric CRS, particularly in areas such as antibiotic use and surgical interventions, owing to a lack of sufficient attention. In recognition of this, the Chinese Rhinopathy Research Cooperation Group developed this expert consensus based on a systematic review of the latest literatures from both domestic and international sources, with reference to the latest evidence-based medical evidence worldwide, and in combination with their own clinical experience. The consensus covers various aspects including epidemiology, predisposing factors, pathophysiology, diagnosis and differential diagnosis, as well as treatment strategies such as medical therapy and surgical intervention. It aims to standardize the clinical diagnosis and treatment of pediatric CRS, improve clinical efficacy and patient satisfaction, reduce clinical expenditures, and decrease the occurrence of adverse reactions.
Humans ; Sinusitis/therapy* ; Chronic Disease ; Child ; Consensus ; Anti-Bacterial Agents/therapeutic use*

Respiratory diseases are common， frequently-occurring clinical diseases. As the prevalence rate is increasing year by year， they have become a problem that seriously affects public health. The diseases are mainly located in the lung by traditional Chinese medicine （TCM） syndrome differentiation. Lung governs Qi and controls breathing and is also an organ for the storage of phlegm. Clinically， phlegm and Qi are often used for the treatment. Banxia Houputang （BHT）， originated from Synopsis of the Golden Chamber （《金匮要略》）， was used to treat plum-stone Ai （globus hystericus） at first. It is composed of Rhizoma Pinelliae， Cortex Magnoliae Offcinalis， Poria， Rhizoma Zingiberis Recens， and Folium Perillae， and treats diseases with the core pathogensis of mutual obstruction of phlegm and Qi. BHT has the effects of moving Qi， dissipating mass， descending adverse Qi， and resolving phlegm， which basically correspond to the pathological characteristics of the lungs. Clinical studies have confirmed that modified BHT can be used either alone or in combination with western medicine to treat chronic pharyngitis， asthma， chronic obstructive pulmonary disease， pneumonia， obstructive sleep apnea， upper airway cough syndrome and other respiratory diseases， with significant effects. It effectively improves the symptoms and signs of the diseases and reduces the recurrence rate. Basic research has shown that BHT plays anti-inflammatory， anti-oxidative stress， anti-apoptotic， autophagy-regulating， and iron overload-regulating roles by regulating the targets in multiple pathways. This paper， by combing the relevant literature in recent years， conducted a systematic review on BHT from the three aspects of syndrome analysis， clinical treatment research and mechanism research， with a view to providing theoretical basis and reference for the mechanism research of BHT in treating respiratory diseases and for expanding its clinical application.

ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance （IR） by inhibiting the advanced glycation end product （AGE）/receptor for the advanced glycation end product （RAGE） signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group， a model group， high-， medium-， and low-dose Yitangkang-medicated serum groups （40， 20， and 10 g·kg^-1）， and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted，the cell viability and glucose consumption level of each group were determined. In addition，the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， p53， cysteinyl aspartate-specific protease-3 （Caspase-3）， and cysteinyl aspartate-specific protease-9 （Caspase-9）］ were determined using Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group， a model group， high-，medium-，and low-dose Yitangkang groups （40， 20， and 10 g·kg^-1）， and a western medicine group （pioglitazone hydrochloride，1.35 mg·kg^-1）. The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin （STZ） in animals and verified by the hyperinsulinemic-euglycemic clamp （HEC） test. After the model was determined successfully， the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group，while Real-time polymerase chain reaction（Real-time PCR） and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2， Bax， p53， Caspase-3， and Caspase-9. Result① In vitro experiments. compared with the blank group， the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group （P<0.01）. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group （P<0.01）. Compared with the blank group， the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.01）. Compared with the model group， the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats （P<0.01） and decreased mRNA and protein expression levels of Bax， p53， Caspase-3， and Caspase-9 （P<0.05， P<0.01）. The medium-dose Yitangkang showed a similar effect as RAGE inhibitor， and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.

Objective:To compare the postoperative adjacent segment degeneration (ASD) between the microscopically anterior cervical discectomy with fusion (ACDF) and anterior cervical corpectomy with fusion (ACCF) in the treatment of cervical spondylotic myelopathy and its influencing factors.Methods:Fifty patients with cervical spondylotic myelopathy treatment in the Qinzhou Second People′s Hospital from July 2018 to July 2020 were selected, they were divided into two groups, 25 patients performed ACDF (ACDF group), and 25 patients performed ACCF (ACCF group). The perioperative period, efficacy and incidence of ASD were compared between the two groups, and the influencing factors of ASD were analyzed.Results:The intraoperative blood loss, operation time, length of hospital stay and postoperative drainage in ACCF group were higher than those in ACDF group: (58.34 ± 8.61) ml vs. (46.77 ± 7.24) ml, (99.57 ± 10.72) min vs. (86.14 ± 9.64) min, (8.97 ± 1.43) d vs. (7.56 ± 1.24) d, (17.92 ± 2.95) ml vs. (14.28 ± 2.66) ml, there were statistical differences ( P<0.05). The postoperative Japanese Orthopaedic Association (JOA) scores and Neck Disability Index (NDI) scores in the two groups were improved significantly ( P<0.05), but the scores of JOA and NDI in the two groups had no significant differences ( P>0.05). The incidence of ASD in the two groups had no significant differences ( P>0.05). The Cox univariate analysis showed that age >59 years, intervertebral disc degeneration, number of fusion segments >2, osteoporosis and postoperative ASD were risk factors for ASD( P<0.05). Conclusions:The effect of microscopically ACDF is similar to that of ACCF in the treatment of cervical spondylotic myelopathy, but ACDF has the advantages of less trauma and quick recovery. The risk of postoperative ASD should be vigilant for patients with age >59 years old, intervertebral disc degeneration, number of fusion segments >2 or osteoporosis.