BACKGROUND: Preclinical studies have indicated that Angong Niuhuang Pills (ANP) reduce cerebral infarct and edema volumes. This study aimed to investigate whether ANP safely reduces cerebral infarct and edema volumes in patients with moderate to severe acute ischemic stroke. METHODS: This randomized, double-blind, placebo-controlled pilot trial included patients with acute ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores ranging from 10 to 20 in 17 centers in China between April 2021 and July 2022. Patients were allocated within 36 h after onset via block randomization to receive ANP or placebo (3 g/day for 5 days). The primary outcomes were changes in cerebral infarct and edema volumes after 14 days of treatment. The primary safety outcome was severe adverse events (SAEs) for 90 days. RESULTS: There were 57 and 60 patients finally included in the ANP and placebo groups, respectively for modified intention-to-treat analysis. The median age was 66.0 years, and the median NIHSS score at baseline was 12.0. The changes in cerebral infarct volume at day 14 were 0.3 mL and 0.4 mL in the ANP and placebo groups, respectively (median difference: -7.1 mL; interquartile range [IQR]: -18.3 to 2.3 mL, P = 0.30). The changes in cerebral edema volume of the ANP and placebo groups on day 14 were 11.4 mL and 4.0 mL, respectively ( median difference: 3.0 mL, IQR: -1.3 to 9.9 mL, P = 0.15). The rates of SAE within 90 days were similar in the ANP (3/57, 5%) and placebo (7/60, 12%) groups ( P = 0.36). Changes in serum mercury and arsenic concentrations were comparable. In patients with large artery atherosclerosis, ANP reduced the cerebral infarct volume at 14 days (median difference: -12.3 mL; IQR: -27.7 to -0.3 mL, P = 0.03). CONCLUSIONS: ANP showed a similar safety profile to placebo and non-significant tendency to reduce cerebral infarct volume in patients with moderate-to-severe stroke. Further studies are warranted to assess the efficacy of ANP in reducing cerebral infarcts and improving clinical prognosis. TRAIL REGISTRATION Clinicaltrials.gov , No. NCT04475328.
Aged ; Female ; Humans ; Male ; Middle Aged ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Ischemic Stroke/drug therapy* ; Pilot Projects ; Stroke/drug therapy* ; Treatment Outcome

BACKGROUND: Stroke is the leading cause of death and long-term disability worldwide, including China. This study aimed to provide timely updates on stroke burden and stroke-related risk factors to help improve population-based prevention and control strategies. METHODS: Based on the Global Burden of Disease study 2021, incidence rate, prevalence rate, mortality rate, and disability-adjusted life-year (DALY) rate were used to estimate stroke burden trend from 1990 to 2021. RESULTS: In 2021, China had 4.1 million incident stroke cases, 26.3 million prevalent stroke cases, 2.6 million stroke related deaths, and 53.2 million stroke related DALYs, compared to 11.9 million incident stroke cases, 93.8 million prevalent stroke cases, 7.3 million stroke related deaths, and 160.5 million stroke-related DALYs worldwide. In 2021, the top six risk factors contributing to stroke burden were high blood pressure, air pollution, tobacco consumption, dietary risk factors, high low-density lipoprotein cholesterol, and high fasting plasma glucose, both in China and worldwide. From 1990 to 2021, China had significant increases of incidence rate, prevalence rate, mortality rate, and DALY rate for stroke, with estimates of 100.6 (95% uncertainty intervals [UI]: 87.2, 114.1)%, 102.9 (95% UI: 95.5, 110.9)%, 40.0 (95% UI: 14.9, 72.3)% and 15.7 (95% UI: -4.6, 41.2)%, respectively, while global incidence rate, prevalence rate, mortality rate and DALY rate for total stroke showed relatively moderate increases or even decreases, with estimates of 15.0 (95% UI: 12.1,18.0)%, 25.8 (95% UI: 23.7, 28.0)%, -2.6 (95% UI: -10.6, 5.5)%, and -10.7 (95% UI: -17.7, -3.6)%, respectively. CONCLUSION Stroke remains a huge disease burden worldwide and in China, and compared to the worldwide China has a significantly higher burden of stroke.
Humans ; Stroke/etiology* ; China/epidemiology* ; Risk Factors ; Global Burden of Disease ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Female ; Quality-Adjusted Life Years ; Male

Objective To explore the effect of Evodiamine (Evo) on the immune function of allergic rhinitis (AR) rats and the regulatory mechanism on C-C motif chemokine ligand 2 (CCL2)/ C-C motif chemokine receptor 2 (CCR2) pathway. Methods The related targets of Evo-AR-immune function were screened by network pharmacology, and the protein interaction network diagram of intersecting targets was constructed. The AR rat model was established by ovalbumin (OVA) combined with aluminium hydroxide, and the rats were divided into six groups: a normal control (NC) group, a model group, a Loratadine (LOR) group, an Evodiamine low dose (Evo-L) group, a Evodiamine high dose (Evo-H) groups, and an Evo-H combined with CCL2 group. After the last administration, the symptoms of rats in each group were scored; ELISA was applied to detect the levels of histamine, immunoglobulin E (IgE), interleukin 4 (IL-4), IL-13 and interferon γ (IFN-γ); Diff-Quick staining solution was applied to detecte the number of cells in the nasal lavage fluid (NALF); hematoxylin eosin (HE) staining was applied to observe the pathological changes of nasal mucosa tissue; real-time quantitative PCR was applied to detect the levels of CCL2 and CCR2 mRNA in tissue; Western blot was applied to detect the expression levels of CCL2, CCR2 and CXC motif chemokine ligand 8 (CXCL8) proteins in nasal mucosa. Results There were eight intersection targets of EVo-AR-immune function, and protein interaction network diagram showed that CXCL8 was the core target. Compared with the NC group, the score of nasal symptoms, the levels of histamine, IgE, IL-4 and IL-13, the numbers of eosinophil, macrophages, neutrophils, lymphocytes and total cells, the mRNA and protein expression levels of CCL2 and CCR2, and the expression of CXCL8 protein in the model group were increased, while the level of IFN-γ was decreased. Compared with the model group, the score of nasal symptoms, the levels of histamine, IgE, IL-4 and IL-13, the numbers of eosinophil, macrophages, neutrophils, lymphocytes and total cells, the mRNA and protein expression levels of CCL2 and CCR2, and the expression of CXCL8 protein in LOR and Evo groups were decreased, while the level of IFN-γ was increased. Further use of CCL2 recombinant protein for compensatory experiments revealed that the improvement effect of Evo on immune function in AR rats was reversed by CCL2. Conclusion Evo can improve the immune function of AR rats, and its mechanism may be related to the inhibition of the CCL2/CCR2 pathway.
Animals ; Receptors, CCR2/immunology* ; Signal Transduction/drug effects* ; Chemokine CCL2/immunology* ; Rats ; Rhinitis, Allergic/metabolism* ; Immunoglobulin E/blood* ; Quinazolines/pharmacology* ; Male ; Interferon-gamma ; Rats, Sprague-Dawley ; Interleukin-13 ; Histamine ; Interleukin-4/immunology* ; Disease Models, Animal

Objective To investigate the effect and mechanism of baicalin on blood lipid metabolism and immune function in rats with gestational diabetes mellitus (GDM). Methods Female rats fed with high-fat and high-sugar diet and male rats fed with ordinary diet were caged together to prepare pregnant rats, and the GDM rat model was established by intraperitoneal injection of streptozotocin (35 mg/kg). GDM rats were randomly divided into a model group, a fasudil (FA) (RhoA/RocK inhibitor) group (10 mg/kg), low-dose (100 mg/kg) and high-dose (200 mg/kg) baicalin groups, and a high-dose baicalin combined with LPA (RhoA/RocK activator) group (200 mg/kg baicalin+1 mg/kg LPA ), with 12 rats in each group. Another 12 pregnant rats fed with high-fat and high-sugar diet were selected as the control group. After 2 weeks of corresponding drug intervention in each group, the level of fasting blood glucose (FBG) was detected by blood glucose meter. The level of fasting insulin (FINS) in serum was detected by ELISA, and the insulin resistance index (HOMA-IR) was calculated. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) in serum, and the levels of immunomodulator tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-10 in peripheral blood were detected by the kit. The histopathological changes of liver were observed by HE staining. The proportion of T lymphocyte subsets in peripheral blood was detected by flow cytometry. The mRNA and protein expressions of Ras homolog gene family member A (RhoA), Rho associated coiled-coil forming protein kinase 1 (ROCK1), and ROCK2 in liver tissue were detected by real-time quantitative PCR and Western blot. Results Compared with the control group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the model group were higher; the level of HDL-C in serum, the percentage of IL-10 levels, CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were lower. Compared with the model group, the levels of FBG, FINS, HOMA-IR, ALT, AST, TG, TC, and LDL-C in serum, the levels of TNF-α, IL-6, the percentage of CD8⁺T cell in peripheral blood, and the mRNA and protein expression of RhoA, ROCK1, and ROCK2 in liver tissue in the the FA group and low-dose and high-dose baicalin groups were lower; the level of HDL-C in serum, IL-10 level, the percentage of CD3⁺T cells, CD4⁺T cell, and CD4⁺T/CD8⁺T ratio in peripheral blood were higher. LPA could obviously weaken the improvement effects of baicalin on blood lipid metabolism and immune function in GDM rats. Conclusion Baicalin may improve blood lipid metabolism and immune function in GDM rats by inhibiting the RhoA/ROCK pathway.
Animals ; Female ; Diabetes, Gestational/metabolism* ; Pregnancy ; rho-Associated Kinases/genetics* ; Flavonoids/pharmacology* ; Rats ; rhoA GTP-Binding Protein/genetics* ; Lipid Metabolism/drug effects* ; Male ; Signal Transduction/drug effects* ; Rats, Sprague-Dawley ; Blood Glucose/metabolism* ; Lipids/blood* ; Tumor Necrosis Factor-alpha/blood* ; rho GTP-Binding Proteins

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 evaluate the predictive effect of the loss of signal (LOS) on the recurrent laryngeal nerve (RLN) injury.Methods:The literatures on PubMed, Web of Science, CNKI, and Wanfang Medical Network database were published before 30 April 2023. English search terms included "thyroid gland surgery" "thyroidectomy" "intraoperative neuromonitoring" "intraoperative nerve monitoring" and "recurrent laryngeal nerve". Chinese search terms included "thyroidectomy", "thyroid surgery" "recurrent laryngeal nerve" "intraoperative nerve monitoring". Two evaluators screened the literature, extracted the materials and evaluated the risk of bias of the study independently. If there were different opinions, researchers should resolve which through consultation and ask the third-party researcher when necessary. The Meta-analysis was performed with the Review Manager 5.4 software.Results:A total of thirty-three studies were included and were all analyzed for primary outcome measures while only twenty-six of which were analyzed for secondary outcome measures. Meta-analysis showed that the positive predictive value of LOS in intraoperative nerve monitoring (IONM) was 65% [ OR=1.88, 95% CI: 1.36-2.60]. Then these thirty-three articles included in IONM were divided into I-IONM, C-IONM and mixed groups. Subgroup analysis showed that the positive predictive value of LOS in I-IONM, C-IONM and mixed groups were 62% [ OR=1.63, 95% CI: 1.05-2.52], 75% [ OR=2.93, 95% CI: 1.64-5.22] and 70% [ OR=2.38, 95% CI: 1.77-3.12] respectively. When these thirty-three included articles were divided into Asian, European, North American and Oceania, subgroup analysis showed that the positive predictive value of LOS was 50% [ OR=1.01, 95% CI: 0.44-2.31], 70% [ OR=2.29, 95% CI: 1.60-3.28], 82% [ OR=4.68, 95% CI: 3.79-5.78] and 83% [ OR=4.81, 95% CI: 3.10-7.46] respectively. Meta-analysis of secondary outcome measures in twenty-six articles showed that the negative predictive value of LOS was 99.6% [ RD=1.51, 95% CI: 1.48-1.53], with the sensitivity of 89% [ RD=1.24, 95% CI: 1.11-1.37] and specificity of 98%[ RD=1.43, 95% CI: 1.40-1.47]. Conclusion:The occurrence of LOS during IONM in thyroidectomy has a positive prediction effect and a higher negative prediction effect, sensitivity and specificity on RLN injury.

Sarcomatoid carcinoma of the renal pelvis accounts for a very low percentage of malignant tumors in the renal pelvis and has a poor prognosis. This article reported a patient with sarcomatoid carcinoma of the renal pelvis. The patient presented with macroscopic hematuria as the first symptom, and CT suggested left renal occupancy, unilateral nephrectomy was performed, and pathology suggested sarcomatoid carcinoma of the renal pelvis. Three weeks after surgery, a follow-up CT showed tumor recurrence. Programmed death 1(PD-1)inhibitor was given once every 3 weeks. Repeated CT examination after 24 weeks of continuous treatment suggested that the recurrent tumor disappeared. The patients was followed-up for 42 months without tumor recurrence or metastasis.

Objective To analyze the differences in static balance plantar pressure characteristics between female adolescent idiopathic scoliosis(AIS)patients with moderate Lenke 3CN and healthy adolescents of the same age,and provide a scientific basis for scoliosis screening,assessment,treatment,and prognosis evaluation.Methods A total of 30 female patients with moderate Lenke 3CN AIS as the AIS group and 30 healthy female adolescents of the same age as the control group were selected,respectively.The plantar pressure data of the subjects were collected,and the characteristics of equilibrium plantar pressure distributions in two groups were comparatively analyzed.Results Regarding the plantar pressure characteristics,the average pressure(P<0.05)and hindfoot pressure(P<0.05)of the left and right foot in the AIS group were significantly greater than those of the control group,the forefoot pressure was significantly lower than that of the control group(P<0.05),and the symmetry index(SI)of both feet was significantly greater than that of the control group(P<0.05).The plantar pressure of the left foot in the AIS group was significantly larger than that of the control group in the medial mid-foot area and 1st toe area(P<0.05),and significantly smaller than that of the control group in the 1st,2nd,3rd,4th and 5th metatarsal areas(P<0.05);the plantar pressure of the right foot in the AIS group was significantly greater than that of the control group in the medial heel area and the1st toe area(P<0.05),and significantly smaller than that of the control group in the lateral mid-foot area,the 3rd,4th,5th metatarsal area and 3rd,4th,5th toe area(P<0.05);and the plantar pressure in the right foot of the AIS group was significantly smaller than that of the control group in the medial heel area and 1st toe area(P<0.05).The plantar pressures at lateral midfoot area,the 3rd,4th,5th metatarsal area and the 3rd,4th,5th toe area of the right foot were significantly larger than those of the control group(P<0.05).Regarding the center of pressure(COP),the length of the COP trajectory,the ellipse area of the 95%confidence interval,the maximum distance of COP left-right movement(COP-X),and the maximum distance of COP anterior-posterior movement(COP-Y)of the AIS group were significantly larger than those of the control group(P<0.05).Conclusions There are significant differences in static balance plantar pressure characteristics between female AIS patients with moderate Lenke 3CN and healthy female adolescents of the same age,with foot pressure favoring the side of the lateral convexity,poorer symmetry and stability of the feet,and weaker balance control.

Objective:To analyze the effect of different gastric mucosa preparation programs on the quality of painless gastroscopy, so as to provide reference for developing mucosal preparation programs.Methods:This was a prospective, randomized controlled study. A total of 150 patients with painless gastroscopy from March 2021 to December 2022 in Shanxi Yuncheng Central Hospital were selected by convenience sampling in this study, they were assigned to control group, water group, and soda water group by random digits table method, each group contained 50 patients. All patients received oral administration of pronase + dimeticone + sodium bicarbonate solution. In addition, control group: prohibited from drinking 4 hours before examination; water group: drinking 200 ml of pure water 2 hours before examination; and soda water group: drinking 200 ml of soda water 2 hours before examination. The clarity score of gastric mucosa and the detection rate of small lesions were compared among the three groups.Results:There were 28 males and 22 females in the control group, aged (47.62 ± 13.83) years old. There were 30 males and 20 females in the water group, aged (44.68 ± 13.61) years old. There were 24 males and 26 females in the soda water group, aged (46.92 ± 12.79) years old. The difference of esophagus, gastric body, gastric antrum and total mucosal clarity scores among the three groups were statistically significant ( F values were 3.68-25.75, all P<0.05). Multiple comparison showed that the esophagus, gastric antrum and total mucosal clarity scores were (1.87 ± 0.58), (1.37 ± 0.34), (6.72 ± 0.92) points in the control group, which were higher than (1.47 ± 0.41), (1.18 ± 0.31), (5.97 ± 0.86) points in the water group, and (1.42 ± 0.41), (1.02 ± 0.22), (5.50 ± 0.79) points in the soda water group, the differences were statistically significant ( t values were 2.67-5.95, all P<0.05). The gastric antrum and total mucosal clarity scores in the water group were higher than in the soda water group, the differences were statistically significant ( t=7.11, 2.71, both P<0.05). The gastric body mucosal clarity score was (1.98 ± 0.74) points in the control group, which was higher than (1.64 ± 0.54) points in the soda water group, the difference was statistically significant ( t=2.66, P<0.05). The gastroscopy examination time and flushin times were (135.20 ± 21.60) s and (1.37 ± 0.43) times in the control group, while (115.52 ± 14.74) s, (0.90 ± 0.29) times and (107.48 ± 13.02) s, (0.62 ± 0.23) times in the water group and soda water group, the control group was higher than the water group and the soda water group, and the water group was also higher than the soda water group, the differences were statistically significant ( t values were 2.38-11.40, all P<0.05). However, there was no statistically significant difference in the detection rate of small lesions among the three groups (all P>0.05). Conclusions:Drinking soda water 2 hours before painless gastroscopy can significantly improve the clarity of patients′gastric mucosa, shorten the examination time and reduce flushing times, but it does not improve the detection rate of small lesions.

Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.