ObjectiveTo investigate the possible mechanism of Shenfuhuang Formula （参附黄配方） in prevention and treatment of epsis-associated encephalopathy from the perspective of brain genomics. MethodsC57BL/6 mice were randomly divided into sham surgery group， sepsis group， and Shenfuhuang group， with 20 mice in each group. The sepsis group and Shenfuhuang group were induced to develop sepsis by cecal ligation and puncture （CLP） procedure. At 4 hours after modelling， Shenfuhuang group were gavaged with 2.5 g/（kg·d） of Shenfuhuang Formula， 0.5 ml each time， at 12 hours intervals， for a total of 4 times after modelling. Sepsis group and sham surgery group were given 0.5 ml of purified water orally. At 48 hours after modeling， the transcriptome sequencing was used to explore the differential gene expression in the effects of Shenfuhuang Formula on the brain regions of septic mice， and real-time PCR and ELISA were later used to further validate the differential gene and proteins expression. ResultsA total of 4605 genes were differentially expressed in Shenfuhuang group compared with sepsis group， of which 2353 genes were up-regulated and 2252 genes were down-regulated. According to the results of previous publications， six key genes were screened， including serine/threonine-protein kinase （Nek1）， myelin-associated glycoprotein （Mag）， endothelial cell-specific tyrosine kinase receptor （Tek）， a disintegrin and metalloproteinase with thrombospondin motifs 20 （Adamts20）， lymphocyte antigen 86 （Ly86）， and E3 ubiquitin-protein ligase （Traip）. Further genetic and protein validation revealed that， compared to the sham surgery group， the mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip in the brain tissue of septic mice significantly reduced （P＜0.05）. In comparison to the sepsis group， Shenfuhuang group showed significantly increased mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip （P＜0.05）. ConclusionThe potential therapeutic targets of Shenfuhuang Formula for treating sepsis-associated encephalopathy may be related to the Nek1， Mag， Tek， Adamts20， Ly86， and Traip genes and their encoded proteins.

Osteoarthritis （OA） is a common degenerative joint disease with a rising incidence rate year by year. Treatment often relies on analgesics and non-steroidal anti-inflammatory drugs （NSAIDs）， which can lead to gastrointestinal damage with long-term use and the recurrence of symptoms. Chinese medicine has a long history of preventing and treating OA， with widespread application and fewer side effects. It offers unique advantages such as a broad treatment scope， multiple targets， and pathways. The effective components of Chinese medicine can reduce the content of reactive oxygen species （ROS）， relieve oxidative stress （OS） damage， and increase the antioxidant capacity of the body by interfering with the expression of biomarkers of OS response such as malondialdehyde （MDA） and superoxide dismutase （SOD）. Through the modulation of signaling pathways such as nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa B （NF-κB）， c-Jun N-terminal kinase （JNK）， NOD-like receptor protein 3 （NLRP3）， and osteoprotegerin （OPG）， they downregulated the expression of inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α）， thereby effectively relieving local joint inflammation， protecting chondrocytes and bone tissue， inhibiting chondrocyte apoptosis， and further alleviating the progression of OA. Currently， there are still certain limitations in the medical research status and development trends of OA， necessitating the continued advancement of traditional Chinese medicine. This paper reviewed the literature on the regulation of OS response by effective components of Chinese medicine for the prevention and treatment of OA， providing new directions and ideas for future research.

Objective:To assess the long-term outcome of sequential radical surgery after immune combined with targeted therapy for patients with initially unresectable hepatocellular carcinoma (HCC).Methods:Clinical data of 100 patients with initially unresectable HCC undergoing sequential radical surgery after immune combined with targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery of Chinese PLA General Hospital from December 2018 to August 2023 were prospectively collected, including 87 males and 13 females, with a median age of 55 (24-73) years. The pre-treatment tumor staging was determined using the China liver cancer staging (CNLC). The efficacy of immune combined with targeted therapy was accessed using the modified response evaluation criteria in solid tumor (mRECIST). The cycles of immune combined with targeted therapy were analyzed. The tumor residual of resected tissue was analyzed through a standard pathological protocol. The prognosis was analyzed using the Kaplan-Meier method.Results:Upon initial diagnosis, there were 46 cases (46.0%) staged CNLC-Ⅲa and 40 (40.0%) staged CNLC-Ⅲb. There were also 14 cases (14.0%) staged CNLC-Ⅰb, Ⅱa, and Ⅱb who underwent immune combined with targeted therapy due to rupture of tumor or insufficient liver remnant. All patients received a median of 5 (3-28) cycles of immune combined with targeted therapy and underwent radical surgery after successful conversion. According to mRECIST, 14 (14.0%) were determined as complete remission, 63 (63.0%) as partial remission, 18 (18.0%) as stable disease, and 5 (5.0%) as disease progression. Of 24 (24.0%) were defined as pathologically complete remission by postoperative pathology. Furthermore, pathological tumor residue was less than 10% in 61 (61.0%) cases and less than 50% in 82 (82.0%) cases. The 1, 3, and 5 year-overall survival rates of patients were 98.0%, 83.1%, and 74.5%, respectively. The 1, 2 and 3 year-recurrence-free survival rates were 67.5%, 54.8%, and 49.6%, respectively.Conclusion:Sequential radical surgery after immune combined with targeted therapy benefits the long-term survival of patients with initially unresectable HCC.

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.

Heart failure is the leading cause of death worldwide. Compound Danshen Dripping Pill (CDDP) or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China. However, the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown. We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E (ApoE) and LDL receptor (LDLR) dual deficient (ApoE^-/-LDLR^-/-) mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure. CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis. Mechanistically, both Wnt and lysine-specific demethylase 4A (KDM4A) pathways were significantly activated in mice with heart injury. Conversely, CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors. While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity. In addition, CDDP attenuated simvastatin-induced myolysis in skeletal muscle. Taken together, our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

【Objective】 To investigate the effect of Qingkailing injection on platelet function preserved in vitro. 【Methods】 A total of 15 bags of plateletpheresis (≥250 mL/bag), adding Qingkailing injection(1.25 mL/bag) at the final concentration of 1%, were stored at 22 ℃ with gentle agitation as the experimental group, and samples were collected on day 1, 3, 5, 8, 10 and 14 to detect the thromboelastogram (TEG), CD62p expression rate and mitochondrial membrane potential (JC-1). The control group was set up synchronously, with the same volume and storage conditions as the experimental groups, and samples were taken on day 1, 3 and 5 after preservation to undertake the same test items as the experimental groups. The differences of detection indexes between the two groups were compared. 【Results】 1) In the experimental group, there was no significant change in K and α during day 1 to 14(P>0.05). The R value (min) increased from 6.12±1.58 to 11.02±2.26, and the CI value changed from 0.27±1.24 to -10.47±3.51 (P<0.05). The MA value (mm) had no significant change within 5 days (P>0.05), but decreased to 53.18±2.71 on day 8 and 22.88±3.45 on day 14 (P<0.05). In the control group during day 1 to 5, K(min) and α showed no significant change, while R(min) was significantly prolonged, MA (mm) decreased and CI increased significantly (P<0.05). 2) The expression rate of CD62p (%) was 70.50±9.12 in the experimental group on day 5 (vs 83.16±5.33 in the control groups, P<0.05) and 82.77±7.17 on day 14 (P<0.05). 3) There was no significant change in JC-1 (%) during regular preservation period between the experimental group and control group (P>0.05), but JC-1 (%) was 86.75±3.88 vs 70.36±19.8 on day 5 (P<0.05). In the experimental group, JC-1(%) was 81.04±9.50 vs 71.38±8.77 vs 82.77±7.17 on day 8, 10 and 14, respectively. 【Conclusion】 The activation and aggregation as well as anti-apoptosis function of plateletpheresis, adding Qingkailing injection at the final concentration of 1%, are similar to those of routine preservation.

Objective? To explore the correlation between preoperative cognitive function and anxiety and depression in patients with laryngocarcinoma. Methods? Totally 42 patients with laryngocarcinoma who were hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of 2 ClassⅢ Grade A Hospitals in Shanxi Province from September 2017 to September 2018 were selected into the observation group by convenient sampling, while 40 healthy volunteers were included in the control group. They were investigated with Self-Rating Anxiety Scale (SAS),Self-Rating Depression Scale (SDS) and Montreal Cognitive Assessment (MOCA). Results? The preoperative SAS and SDS scores of the observation group were (41.48±5.46) and (43.69±6.16) respectively, both higher than those of the control group (t=4.189, 6.234; P＜ 0.01); the preoperative MOCA score of the observation group was (22.90±4.13), lower than that of the control group (t=2.646, P＜ 0.01). Correlation analysis showed that the laryngocarcinoma patients＇ anxiety and depression were negatively correlated with their cognitive function (r=-0.750, -0.660; P＜0.01). Conclusions? Compared with the healthy volunteers, the laryngocarcinoma patients are more susceptible to anxiety, depression and cognitive disorder. The severer their anxiety and depression, the poorer their overall cognitive function was.

Objective To investigate the diagnosis and prognosis of patients with coronary artery aneurysm in Kawasaki disease.Methods The data of ultrasonic diagnosis and follow-up of 338 children with Kawasaki disease complicated with coronary artery aneurysms were analyzed.Results The incidence of coronary artery aneurysm in the acute stage of Kawasaki disease was 21.2％ (338/1 594).Of all the 338 cases,small aneurysms was 66.6％ (225 cases),medium aneurysms was 25.1％ (85 cases),and giant aneurysms was 8.3％ (28 cases).There were 719 branches involved in 338 cases,32.8％ of them in left main coronary artery and 31.1％ in right coronary artery;25.3％ in left anterior descending branch,and 10.8％ in left circumflex branch.A total of 382 branches were followed up,including 218 branches of small coronary aneurysm group and 82.1％ of them were completely recovered to the normal diameter.The medium aneurysm group was 124 brunches,the proportion of no significant change,retraction,and normal were 23.4％,68.5％ and 8.1％,respectively.There were 40 brunches in the giant anuerysm group,in which the proportion of no significant change,retraction,and normal were 70.0％,27.5％ and 2.5％,respectively.A total of 30 thrombosiswere detected by echocardiography in the acute stage,20 thrombosis were regularly followed up,12 thrombosis gradually subsided,and the other remained persist.Five thrombosis were detected in the sequelae stage,and all located in the giant coronary aneurysm.Seven children were clinically diagnosed with ischemic heart disease,of them,acute myocardial infarction in 1 case,1 died of heart failure.Conclusions Kawasaki disease coronary artery disease are common in small coronary aneurysms,of which the left main artery and right coronary artery lesions are the most common,and the prognosis is better;medium and giant aneurysm need more time to recovery,and are easy to complicated with thrombosis.

Objective To observe the effects of acupuncture on oxidative stress and neuronal damage in the prefrontal cortex of chronic cerebral hypoperfusion (CCH) rats; To investigate the molecular mechanisms of acupuncture in cognitive impairment of vascular dementia (VD) rats. Methods The animal model of VD was replicated by permanent bilateral common carotid artery occlusion (2VO) to induce CCH in rats. After modeling, rats were randomized into model group, acupuncture group and non-acupoint group. Sham-operation group was set as control group. Rats of acupuncture group and non-acupoint group were treated with needling for 2 weeks at 3 days after 2VO. Nissl and DHE staining were respectively used to evaluate the numbers of neurons and ROS level. SOD activity was examined by xanthine oxidase technique. Results Compared with sham-operation group, the number of neurons and SOD activity decreased in the model group, while the ROS level increased. Compared with the model group, the number of neurons and SOD activity increased in the acupuncture group, while the ROS level decreased. There were no obvious changes in all indexes in non-acupoint group. Conclusion Acupuncture can inhibit oxidative stress and improve neuronal damage and loss in the prefrontal cortex of VD rats.

OBJECTIVETo discuss the effects on detrusor hyperreflexia treated with ginger-salt-isolated moxibustion at "Shenque" (CV 8) and its mechanism.

METHODSThirty female adult SD rats were selected. The model of detrusor hyperreflexia was prepared with complete spinal transection at T, of which, 20 rats were randomized into a model group (10 rats) and a moxibustion group (10 rats). A sham-operation group (10 rats) was set up for sham-spinal transection. In the moxibustion group, when urine incontinence occurred (about in 2 weeks of modeling), the ginger-salt-isolated moxibustion at "Shenque" (CV 8) was given, 3 moxa cones each time, once a day, continuously for 7 days. After treatment, in each group, the urodynamic parameters were determined, after which, the bladder detrusor was collected. Western blot was used to determine the protein expressions of M2 and M3 receptors.

RESULTSCompared with the sham-operation group, the micturition interval was shortened apparently (<0.01); the maximal bladder pressure was increased apparently (<0.01); the protein expression of M2 receptor in the detrusor was increased significantly (<0.05) and that of M3 receptor had no apparent change (>0.05) in the rats of the model group. Compared with the model group, the micturition interval was longer apparently (<0.01), the maximal bladder pressure was reduced apparently (<0.01), the protein expression of M2 receptor in the detrusor was reduced significantly (<0.05) and that of M3 receptor had no apparent change (>0.05) in the rats of the moxibustion group.Compared with the sham-operation group, the results of the above indicators were not different significantly in the moxibustion group (all>0.05).

CONCLUSIONSThe ginger-salt-isolated moxibustion at "Shenque" (CV 8) suppresses the overactive bladder in the rat with spinal transection and its effect mechanism is possibly relevant with reducing the protein expression of detrusor M2 and inhibiting the excessive contraction of the detrusor.