ObjectiveTo explore the possible mechanisms of Shujin Jiannao Formula （舒筋健脑方） for cerebral palsy. MethodsThirty 7-day-old SD rats were randomly divided into normal group， model group， and Shujin Jiannao Formula group， with 10 rats in each group. The model group and Shujin Jiannao Formula group established a cerebral palsy model by the classic Rice-Vannucci method. After successful modeling， rats in Shujin Jiannao Formula group were given Shujin Jiannao Formula 16 g/（kg·d） by gavage， while the normal group and model group were given normal saline 10 ml/（kg·d） by gavage once a day. After one week of intervention， the rats' body weight was measured， and Zea-Longa scores， the righting reflex test， and the hindlimb suspension test were conducted for assessment； hematoxylin-eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissue， and the number of Nissl-positive neurons was counted； enzyme-linked immunosorbent assay （ELISA） was employed to measure levels of inflammatory cytokines in the brain tissue， specifically interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； immunofluorescence was used to detect the expression levels of neurofilament protein 200 （NF200） and myelin basic protein （MBP） in brain tissue； Western Blot analysis was conducted to determine the protein levels of phosphoinositide 3-kinase （PI3K）， protein kinase B （Akt/PKB/Rac）， and mammalian target of rapamycin （mTOR） in brain tissue. ResultsCompared with the normal group， rats in the model group showed significantly higher Zea-Longa scores and lower scores in the hindlimb suspension test （P＜0.01）； pathological findings revealed loose structure in the cerebral cortex， hippocampal atrophy， and neuronal damage in brain tissue. Levels of IL-1β and TNF-α elevated， and the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region reduced， and immunofluorescence intensity of NF200 and MBP， as well as protein expression levels of PI3K and mTOR， significantly decreased （P＜0.05 or P＜0.01）. Compared with the model group， rats in Shujin Jiannao Formula group showed decreased Zea-Longa scores and increased hindlimb suspension test scores （P＜0.05）； pathological damage in brain tissue alleviated， levels of IL-1β and TNF-α reduced， the number of Nissl-stained positive neurons in the cortex and hippocampal CA1 region increased， and the immunofluorescence intensity of NF200 and MBP， as well as the protein levels of PI3K and mTOR， significantly elevated （P＜0.05 or P＜0.01）. There were no statistically significant differences among the groups in body weight， body-turning time， or AKT protein levels in brain tissue （P＞0.05）. ConclusionShujin Jiannao Formula can improve the neurological function of rats with cerebral palsy， exert neurorestorative effects， and its mechanism of action may be related to the reduction of inflammatory response in brain tissue and the activation of the PI3K/AKT/mTOR signaling pathway.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Objective To analyze serum characteristics and determine the reference range for thyroid function among healthy 11～16 year-old teenagers in Xi'an in order to offer a theoretical basis for clinical diagnosis and therapy.Methods A sum of 1 378 healthy 11～16 year-old teenagers who met the inclusion criteria from the First Affiliated Hospital of the Air Force Medical University(Xijing Hospital)between January 2020 and December 2022 were selected as research subjects,including 628 males and 750 females.They were divided into three groups based on age:Group 1:11～＜13 year-olds(433 cases),Group 2:13～＜15 year-olds(425 cases),and Group 3:15～≤16 year-olds(520 cases).Differences in serum thyroid function indices among different genders and age groups were analyzed,the reference ranges for these indices were established,and 99 healthy 11-16 year-old teenagers who met the inclusion criteria were chosen for verification.Results There were no significant differences between different genders in thyroid stimulating hormone[TSH,2.56(1.80,3.63)μIU/ml vs 2.43(1.68,3.48)μIU/ml]and total thyroxine[TT4,97.84(85.34,111.00)nmol/L vs 98.20(87.16,111.23)nmol/L],the differences were statistically significant(Z=-1.881,-0.638,all P＞0.05).Meanwhile,the differences in free thyroxine[FT4,16.93(15.49,18.60)pmol/L vs 16.26(14.80,17.83)pmol/L],free triiodothyronine[FT3,6.21(5.66,6.80)pmol/L vs 5.59(4.98,6.19)pmol/L],and total triiodothyronine[TT3,2.24(1.96,2.55)nmol/L vs 2.04(1.78,2.34)nmol/L]between different genders were significant(Z=-5.368,-11.994,-6.417 all P＜0.01).The differences in thyroid function indices were significant among different age groups(Z=10.649～261.003,all P＜0.05).The reference ranges for thyroid function indices across different age groups and genders were established,in which thyroid function indicators were verified to be within the established reference range by 99 samples.Conclusion Teenage hormone secretion varies greatly,and the secretion of thyroid hormones is influenced by various factors.Thus,the diagnosis and treatment of teenage thyroid diseases cannot fully rely on the reference ranges provided by adults or manufacturers.This study established the reference range of the thyroid function indices of 11～16 year-old teenagers in Xi'an,offering clinical doctors'diagnosis and treatment data support.

Objective:To search and summarize the best evidence for preoperative prehabilitation in patients with lung cancer complicated by chronic obstructive pulmonary disease and to inform the management of preoperative prehabilitation in patients with lung cancer combined with COPD by clinical providers.Methods:Systematically guideline websites, professional society websites, evidence-based databases, and comprehensive databases were searched for types of literature including clinical decision making, guidelines, expert consensus, evidence summaries, systematic evaluations, Meta-analyses, and randomized controlled trials. The time for the retrieval was from the inception of databases until October 31th, 2023. And the quality of the included literature was evaluated and evidence was extracted, evaluated the quality of the included literature, and extracted evidence.Results:Finally, 18 articles were included, including 8 guidelines, 8 expert consensus, and 2 systematic reviews. Summarized the 30 best evidence in 4 areas of prerehabilitation: need, timing, location, content (including smoking cessation management, respiratory exercise, exercise, nutritional support, and medication management).Conclusions:This study summarizes the best evidence for preoperative prehabilitation in patients with lung cancer combined with chronic obstructive pulmonary disease, and healthcare professionals should be mindful of the need to develop preoperative prehabilitation protocols judiciously, taking into account the specific clinical context during the subsequent translation of the evidence to the clinic.

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

The relationship between antagonism and symbiosis exists not only in the biological world,but also among the subspecialties of large tertiary grade A general hospitals.In the context of symbiosis theory,the following recommendations based on the four basic elements of subspecialty symbiosis systems were proposed to provide a theoretical basis for exploring the path of high-quality development of subspecialties:enhance the capacity of the symbiosis unit itself and clarify the role of the unit;establish efficient information system and make full use of management platform;improve interest coordination mechanism and strengthen inter-subspecialty ties;implement relevant support policies and solid sense of symbiotic to synergy provide a theoretical basis for exploring pathways for high quality development of subspecialties.

Objective:To explore the association between environment exposure and hormone-sensitive cough in patients with chronic cough.Methods:Clinical data of 197 patients with chronic cough visited outpatient clinic of the Second Affiliated Hospital of Guangzhou Medical University from June 2016 to June 2021 were retrospectively analyzed, including 130 cases of corticosteroid responsive cough (CRC, 66.0%) and 67 cases of non-corticosteroid responsive cough (NCRC, 34.0%). The association between living environment exposure and hormone sensitivity was examined with a binary logistic regression analysis.Results:Among 197 patients with chronic cough, there were 82 males (41.6%) and 115 females (58.4%). 75.1% (148/197) had a history of smoking, and 16.8% (33/197) had a history of allergies. 66.0% (130/197) lived in the city center, 18.3% (36/197) had a chemical factory around their place of residence, 11.2% (22/197) renovated their homes within the first six months of the disease, 15.7% (31/197) purchase new furniture, 54.3% (107/197) plant flowers and plants in their houses, 21.3% (42/197) keep pets in their houses, 79.2% (156/197) had lived in their houses for more than 2 years, 71.1% (140/197) had cockroaches in their houses, 16.2% (32/197) had mold in their houses, 83.3% (164/197) had a frequency of air conditioning cleaning exceeds 2 months per time.There were 130 patients (66.0%) with CRC and 67 patients (34.0%) with NCRC.Binary logistic regression analysis showed that living close to the main road ( OR=2.296, 95% CI: 1.350-3.904, P=0.002), living near chemical factories ( OR=3.322, 95% CI: 2.158-5.573, P<0.001), history of allergy ( OR=2.175, 95% CI: 1.165-4.058, P=0.015), purchasing new furniture within 6 months ( OR=2.828, 95% CI: 1.402-5.706, P=0.004), cotton and linen curtains ( OR=1.875, 95% CI: 1.038-3.388, P=0.037) were positively correlated with CRC; while down and wool pillowcases and quilts ( OR=0.142, 95% CI: 0.033-0.602, P=0.008; OR=0.207, 95% CI: 0.067-0.640, P=0.006) and low ventilation frequency ( OR=0.281, 95% CI: 0.131-0.603, P=0.001) were negatively correlated with CRC. Conclusion:Hormone-sensitive cough patients account the most of chronic cough cases, and there are differences in the living environment exposure between CRC and NCRC patients, which provides information for corresponding interventions to prevent and manage CRC.

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

Objective:To examine the effects of Zishenwan Prescription on bile acid metabolism in mice with diabetic encephalopathy; To explore its mechanism of improvement of diabetic encephalopathy.Methods:Male C57BL/6J mice were used to replicate the mouse model of type 2 diabetes mellitus by using high-fat chow and a single intraperitoneal injection of streptozotocin (120 mg/kg). The mice were screened for diabetic encephalopathy by using the Morris water maze test after 8 weeks of continuous stimulation with hyperglycemia, and were divided into model group and Zishenwan Prescription group according to random number table method, with 12 mice in each group. The mice in the Zishenwan Prescription group were treated with the crude extract of Zishenwan Prescription (9.36 g/kg) by gavage, and the normal group and the model group were treated with the same volume of distilled water once a day for 8 weeks. At the end of the treatment, Morris water maze test was used to investigate the cognitive function of diabetic encephalopathy mice; cresyl violet staining was used to detect the number of granule neurons in the hippocampus; serum and feces were collected to detect the content of bile acids by liquid-liquid coupling; hepatic bile acid synthase CYP7a1 and CYP27a1, farnesol X receptor (FXR), fibroblast growth factor 15 (FGF15), fibroblast growth factor receptor 4 (FGFR4), and ileocecal apical sodium-dependent bile acid transporter protein (ABST) mRNA levels were detected by using fluorescence quantitative PCR assay.Results:Compared with the model group, mice in the Zishenwan Prescription group had shorter evasion latency time ( P<0.05 or P<0.01), decreased time to first reach the platform ( P<0.01), increased number of times to traverse the platform ( P<0.01), and reduced neuronal cell damage in hippocampal area; mice in the Zishenwan Prescription group showed decreased serum and fecal total bile acid content ( P<0.05 or P<0.01); the liver CYP7a1 and CYP27a1 mRNA expressions increased ( P<0.01), and FXR and FGF15 mRNA expressions decreased ( P<0.01); ileal ABST mRNA expression decreased ( P<0.01). Conclusion:Zishenwan Prescription may regulate bile acid metabolism, inhibit FRX-FGF15/FGFR4 signaling and ABST expression to promote new bile acid synthesis and conjugated bile acid reabsorption, and thus improve cognitive function in diabetic encephalopathy mice.