1.Mapping positive validation system of inhalation toxicology cloud exposure system
Yin-Xia LI ; Yun-Hua SHENG ; Yue HU ; Li-Ming TANG
Chinese Pharmacological Bulletin 2024;40(8):1591-1598
Aim To explore the feasibility of the cloud exposure system for in vitro exposure experiments on inhalation toxicology.Methods Calu-3 cells cultured at the air-liquid interface(ALI)were exposed to three concentrations of lipopolysaccha-ride(LPS):high,medium,and low(800,400,200 mg·L-1)by the cloud exposure system,and phosphate buffer solu-tion(PBS)was used as a negative control group for one expo-sure,while the high concentration of LPS was used to expose Calu-3 cells for five times.Calu-3 cells were exposed to phos-phate buffer solution(PBS)once as negative control group and to high concentration of LPS solution for five times,and the ac-tivity of Calu-3 cells,the release of lactate dehydrogenase(LDH),TEER,mucin MUC5AC,and the expression of inflam-matory factors IL-6,IL-8 and TNF-α were detected 3 h and 24 h after the end of the exposure,respectively.Results Compared with the PBS-negative control group,after exposure to the Calu-3 cell model at the air-liquid interface with three concentrations of LPS,high,medium,and low,there were no significant changes in the activity and LDH release,but the cellular electrical resist-ance value was reduced,and the barrier function of the cells was impaired;with the increase of the exposure concentration,the LPS promoted the expression of the cellular mucin MUC5AC,which led to a decrease in the expression of cellular IL-6,IL-8,and a decrease in the expression of TNF-α.Expression of IL-6 and IL-8 decreased and TNF-α expression increased;as the fre-quency of exposure increased,LPS inhibited the expression of mucin and increased the expression of IL-6;an increase in the frequency of exposure along with a prolongation of post-exposure assay time resulted in an increase in the expression of cellular IL-8 and TNF-a.Conclusions The ALI cloud exposure ap-proach can effectively reflect the cellular response to positive subjects,and this in vitro exposure can be used in subsequent exposure experiments to evaluate the inhalation toxicity of com-pounds.
2.Effects of anthoxanthin on the growth,proliferation and in-vasion of human gastric cancer cell line SGC7901
Hao-Yu ZHANG ; Xin KANG ; Bin LI ; Tian-Sheng YIN ; Ya-Jun ZHANG
Chinese Journal of Current Advances in General Surgery 2024;27(4):259-263
Objective:To investigate the effect of anthoxanthin on the proliferation and apopto-sis of human gastric cancer cell line SGC7901 and its possible mechanism.Methods:SGC7901 was cultured in the medium containing different concentrations(0,20,40,80 μ mol/L)of antho-cyanin.Hoechst staining,MTT colorimetry and flow cytometry were used to verify the effect of Form on the inhibition rate,cell cycle,nuclear morphology and apoptosis.Western Blotting was used to test the level of β-Catenin、p-β-Catenin,CyclinD1,CDK4,p-AKT,AKT,BCL-2,BAX,caspase3 and other proteins.The mRNA expression of BCL-2,CDK4,CDK6,AKT,CyclinD1,BAX,Caspase3 was detected by RT-PCR.Results:MTT results showed that the inhibitory effect of Form on SGC7901 was concentration dependent and time dependent.Hoechst staining showed that the cells in the experimental group(20,40,80 μ mol/L),the phenomenon of pyknosis and dissolution of the nucleus,even granular aggregation after rupture.Flow cytometry showed that the apoptosis rate of the experimental group(20 μ mol/L,40 μ mol/L,80 μ mol/L)was 17.0%,21.5%,32.5%respectively after treated with different concentrations of Form for 48 hours,which was positively correlated with the drug concentration.RT-PCR showed that caspase3 and BAX mRNA expression increased with the increase of Form intervention concentration(P<0.01);the mRNA expression of BCL-2,CDK4,CDK6,AKT,CyclinD1 decreased(P<0.01).WB results showed that β-Catenin、p-β-Catenin,Cy-clinD1,CDK4 and p-AKT,AKT,BCL-2 decreased with the increase of Form intervention concentra-tion(P<0.01);The relative expression of caspase3,BAX and other proteins increased(P<0.01).Con-clusion:Form can promote apoptosis of SGC7901,and the possible mechanism is to inhibit Wnt/β-Catenin signal;it also mediates the activation of Caspase family.
3.Exploration of the Effect and Mechanism of Tiaoqi Zhike Prescription on Airway Inflammation in Rats with Cough Variant Asthma Based on MAPK/NF-κB Signalling Pathway
Chunying LI ; Yanyan YIN ; Mengyao JI ; Xiyu ZHANG ; Chen XU ; Sheng WANG
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(7):1008-1015
Objective To investigate the effects and mechanisms of Tiaoqi Zhike Prescription(Ephedrae Herba,Armeniacae Semen Amarum,Fritillariae Thunbergii Bulbus,Scutellariae Radix,Trichosanthis Semen,etc.)on airway inflammation in cough variant asthma rats based on the MAPK/NF-κB signaling pathway.Methods Cough variant asthma rat model was established by ovalbumin sensitization.SD rats were randomly divided into blank group,model group,Dexamethasone group(0.5 mg·kg-1),Montelukast group(1.0 mg·kg-1)and Tiaoqi Zhike Prescription low-,medium-and high-dose groups(9.6,19.2,38.4 g·kg-1),with 10 rats in each group.Intragastric administration was given once a day for 14 consecutive days.The general condition of rats was observed and the number of coughs in rats within two minutes after atomization was recorded.HE staining and Masson staining were used to observe the pathological changes of lung tissue in rats.The levels of serum interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)were detected by ELISA.The protein expression levels of p38 MAPK,p-p38,NF-κB p65 and p-p65 in lung tissue were detected by Western Blot.The mRNA expression levels of p38 MAPK and NF-κB p65 in lung tissue were detected by RT-qPCR.Results Compared with the blank group,the times of coughs in the model group was significantly increased(P<0.01),and the pathological score of lung injury and the area ratio of collagen fibers were significantly increased(P<0.01).The levels of serum IL-1β,IL-6 and TNF-α were significantly increased(P<0.01).The protein expressions of p-p38,p-p65,p-p38/p38 and p-p65/p65 in lung tissue were significantly up-regulated(P<0.01),and the mRNA expressions of p38 MAPK and NF-κB p65 were significantly up-regulated(P<0.01).Compared with the model group,the cough frequency of rats in each administration group was significantly decreased(P<0.01),the pathological score of lung injury and the area ratio of collagen fibers were significantly decreased(P<0.01),the levels of serum IL-1β,IL-6 and TNF-α were significantly decreased(P<0.01),and the protein expressions of p-p38 and p-p65 and the mRNA expressions of p38 MAPK and NF-κB p65 in lung tissue were significantly down-regulated(P<0.05,P<0.01).The protein expression ratios of p-p3/p38 and p-p65/p65 in the lung tissue of rats in the high-dose group of Tiaoqi Zhike Prescription were significantly down-regulated(P<0.01).Compared with the Dexamethasone group and the Montelukast group,the number of coughs in the high-dose group of Tiaoqi Zhike Prescription was significantly reduced(P<0.05).Compared with the Dexamethasone group,the serum levels of IL-1β,IL-6 and TNF-α in the high-dose group of Tiaoqi Zhike Prescription were significantly decreased(P<0.01).Compared with the Montelukast group,the levels of serum IL-1β and TNF-α in the high-dose group of Tiaoqi Zhike Prescription were significantly decreased(P<0.05,P<0.01).Conclusion Tiaoqi Zhike Prescription can improve the cough symptoms of ovalbumin-induced cough variant asthma model rats,reduce airway inflammatory cell infiltration and airway remodeling,and reduce the levels of inflammatory cytokines IL-1β,IL-6 and TNF-α.The mechanism may be related to the regulation of MAPK/NF-κB signaling pathway.
4.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
5.Chest computed tomography manifestations in neonates with chronic granulomatous disease
Heng SHU ; Li-Li WANG ; Tong-Sheng YE ; Xian-Hong LIN ; Shao-Hua BI ; Yu-Hong ZHAO ; Ping-Sheng WANG ; Li-Yin DAI
Chinese Journal of Contemporary Pediatrics 2024;26(7):730-735
Objective To study chest computed tomography(CT)manifestations in neonates with chronic granulomatous disease(CGD)to provide clues for early diagnosis of this disease.Methods A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital.Results Nine neonates with CGD were included,with eight presenting respiratory symptoms as the initial sign.Chest CT findings included:consolidation in all 9 cases;nodules in all 9 cases,characterized by multiple,variably sized scattered nodules in both lungs;masses in 4 cases;cavities in 3 cases;abscesses in 6 cases;bronchial stenosis in 2 cases;pleural effusion,interstitial changes,and mediastinal lymphadenopathy each in 1 case.CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement;no signs of pulmonary emphysema,lung calcification,halo signs,crescent signs,bronchiectasis,or scar lesions were observed.There was no evidence of rib or vertebral bone destruction.Fungal infections were present in 8 of the 9 cases,including 6 with Aspergillus infections;three of these involved mixed infections with Aspergillus,with masses most commonly associated with mixed Aspergillus infections(3/4).Conclusions The primary manifestations of neonatal CGD on chest CT are consolidation,nodules,and/or masses,with Aspergillus as a common pathogen.These features can serve as early diagnostic clues for neonatal CGD.
6.Research progress on the mechanism of traditional Chinese medicine intervening in esophageal cancer by microRNA regulation
Zhiwen SHEN ; Liqun LI ; Mingyao XU ; Xin LIU ; Jing HUANG ; Xiaoning ZHANG ; Jiaqi YIN ; Sheng XIE
China Pharmacy 2024;35(8):1016-1022
Esophageal cancer (EC) is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA (miRNA) is an important regulator in tumor occurrence and development, and can participate in malignant biological behaviors such as tumor cell proliferation, invasion, metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects, wide range of effects, and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine (including curcumin, Tussilago farfara polysaccharides, Atractylodes macrocephala polysaccharides and ophiopogonin B) and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p (miR-532-3p), miR-551b-3p, miR-99a, miR-34a, miR-199a-3p and miR-377; and the active ingredients/parts of traditional Chinese medicine (including chrysin and Actinidia arguta extract), and Chinese herbal formulas (including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction) could down-regulate the expressions of miRNAs such as miR-199a-3p, miR-451 and miR-21, which could regulate the expressions of signaling pathways (phosphoinositide 3-kinase/protein kinase B, etc.) or their downstream protein(zinc-finger and homeobox protein 1, etc.) or enzymes(thymidine kinase-1, etc.), inhibit the proliferation, invasion and metastasis of EC cells and induce apoptosis, thereby ultimately achieving the purpose of preventing the disease from aggravating.
7.Effects of distal tibial tuberosity-high tibial osteotomy on ankle angle on coronal plane
Yuetong YIN ; Guangyu ZHU ; Xiangdong TIAN ; Yetong TAN ; Sheng MA ; Zhipeng XUE ; Yuanyi HU ; Xiaomin LI
Chinese Journal of Tissue Engineering Research 2024;28(21):3349-3354
BACKGROUND:Distal tibial tuberosity-high tibial osteotomy is a surgical treatment for knee osteoarthritis,but there is still a lack of clinical studies on its effect on ankle joints. OBJECTIVE:To observe the effects of distal tibial tuberosity-high tibial osteotomy on ankle angle on coronal plane of the radiography of the full length of lower limb in weight loading. METHODS:Data of 40 patients(41 knees)with distal tibial tuberosity-high tibial osteotomy from March 2021 to March 2022 were retrospectively analyzed,including 31 females and 9 males,20 left knees and 21 right knees,aged 49-75 years,mean(63.44±6.57)years.The radiographic data of the full length of the lower limb in weight loading were collected before,week 2 and week 48 postoperatively.Hip-knee-ankle angle,talar tilt angle,tilt angle of the ankle,tibiocrural angle,and tibial articular surface angle were measured before and after surgery. RESULTS AND CONCLUSION:(1)Hip-knee-ankle angle improved from(-6.24±3.69)° before operation to(2.59±3.49)° week 2 postoperatively and(2.15±3.49)° week 48 postoperatively.The tilt angle of the ankle changed from(-7.90±3.11)° before operation to(-2.51±2.59)° week 2 postoperatively and(-2.46±2.42)° week 48 postoperatively,with statistically significant difference(P<0.001).(2)There was no significant difference in talar tilt angle,tibiocrural angle,and tibial articular surface angle before and week 2 postoperatively.(3)No significant difference in the angle changes was detected between week 2 and week 48 postoperatively.(4)It is indicated that distal tibial tuberosity-high tibial osteotomy can not only correct genu varus but also improve ankle angle.This result remains stable after 48 weeks of weight-bearing activities.
8.Clinical Study of Modified Shenqi Pill (肾气丸) Plus Tongdu Tiaoshen Acupuncture (通督调神针刺) for Neurogenic Bladder After Spinal Cord Injury of Kidney-Yang Deficiency Syndrome
Meiyan GUO ; Qian FAN ; Yan LI ; Bao YIN ; Sheng JIANG
Journal of Traditional Chinese Medicine 2024;65(2):192-197
ObjectiveTo observe the clinical efficacy of modified Shenqi Pill (肾气丸) plus Tongdu Tiaoshen Acupuncture (通督调神针刺) in the treatment of neurogenic bladder after spinal cord injury of kidney-yang deficiency syndrome. MethodsForty-six patients were randomly divided into 23 cases each in the control group and the treatment group. Both groups were given conventional treatment, i.e. oral methylcobalamin tablets (0.5 mg each time, 3 times a day) and paraplegic conventional acupuncture (once a day, 6 consecutive days a week). The control group was given simple bladder function rehabilitation training on the basis of the conventional treatment; and the treatment group was given modified Shenqi Pill orally (1 dose a day, 150 ml each time, taken warmly in morning and evening) and Tongdu Tiaoshen Acupuncture (once a day, 6 consecutive days per week) in addition to what were given to the control group. The treatment course lasted for 4 weeks. The 24 h urination frequency, 24 h urine leakage frequency, 24 h single urine volume, bladder residual urine volume, international lower urinary tract symptom (LUTS) score, traditional Chinese medicine (TCM) syndrome score were compared between the two groups, and clinical effectiveness and TCM syndrome effectiveness were compared between the two groups after treatment. ResultsTwenty patients in each group were finally analyzed in this study. The number of 24 h urination, the number of 24 h urine leakage, bladder residual urine volume, LUTS score, and the TCM syndrome scores decreased after treatment in both groups, and the 24 h single urine volume increased (P<0.01); and much more improvement was found of each index in the treatment group than in the control group (P<0.05 or P<0.01). The total clinical effectiveness and TCM syndrome effectiveness in the treatment group was 85.00% (17/20) respectively, which were statistically significantly higher than 45.00% (the total clinical effectiveness, 9/20) and 60.00% (TCM syndrome effectiveness, 12/20) in the control group (P<0.01). ConclusionModified Shenqi Pill plus Tongdu Tiaoshen Acupuncture can signi-ficantly improve the clinical symptoms of neurogenic bladder patients after spinal cord injury of kidney-yang deficiency syndrome, having better effectiveness than simple bladder function rehabilitation training, and its mechanism may be related to the improvement of the injured nerve function innervating the bladder.
9.Research progress about traditional Chinese medicine in the intervention of gastric cancer by regulating Th17/Treg balance
Jiaqi YIN ; Liqun LI ; Sheng XIE
China Pharmacy 2024;35(3):379-384
Gastric cancer (GC) is a common malignant tumor of the digestive tract. T helper cells 17 (Th17) and T regulatory cells (Treg) are differentiated subsets of CD4+T cells. Th17/Treg imbalance has been shown to be closely related to the progression of GC. Traditional Chinese medicine (TCM) can not only improve the survival prognosis of GC patients, but also play a role in enhancing the efficacy and reducing the toxicity of postoperative chemotherapy for GC. This paper systematically sorted out the action rules of TCM in the intervention of GC by regulating Th17/Treg balance. The results showed that the TCM compound could regulate the balance of GC Th17/Treg by invigorating the spleen and invigorating Qi, warming Yang, removing blood stasis and detoxifying. The mechanism of regulating Th17/Treg balance in the intervention of GC is mainly to inhibit the excessive differentiation of Th17 and Treg and the overexpression of transcription factors and cytokines, reverse the excessive drift of GC Th17/Treg balance to Th17 or Treg, and thus restore the immune balance of GC Th17/Treg.
10.Role of NF-κB Signaling Pathway in "Reflux Esophagitis-esophageal Cancer" and Traditional Chinese Medicine Intervention:A Review
Mingyao XU ; Liqun LI ; Xin LIU ; Zhiwen SHEN ; Xiaoning ZHANG ; Jing HUANG ; Jiaqi YIN ; Zhu LIU ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):221-233
Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise, and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa, causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue, which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B (NF-κB) signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation, autophagy, apoptosis, and inflammatory response of esophageal epithelial cells and tumor cells, accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently, there is no specific treatment for reflux esophagitis and esophageal cancer, and large side effects often appear. Therefore, finding a promising and safe drug remains a top priority. In recent years, traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway, and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, but there is a lack of comprehensive and systematic elaboration. Therefore, this paper summarized the relevant studies in recent years, analyzed the relationship among NF-κB signaling pathway, reflux esophagitis, esophageal cancer, and transformation from inflammation to cancer, and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer, so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

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