Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

OBJECTIVE: To explore the clinical efficacy of orthopedic manipulation combined with daoyin exercises in the treatment of chronic lumbar disc herniation under the guidance of the theory of "equal emphasis on muscles and bones". METHODS: A total of 60 patients with single-segment, unilateral chronic lumbar disc herniation from January 2023 to January 2024 were randomly divided into the traditional physical therapy group and the manipulation treatment group, with 30 cases in each group. Among them, 3 cases were lost to follow-up in the traditional physical therapy group and 2 cases in the manipulation treatment group. There were 27 cases in the traditional physical therapy group, including 15 males and 12 females, aged 25 to 65 years old with an average of (51.96±14.42) years;the course of disease ranged from 3 to 15 months with an average of (9.89±3.32) months;11 cases were on the left side and 16 cases on the right side;15 cases were at the L4, 5 segment and 12 cases at the L5S1 segment. They were treated with lumbar traction, medium-frequency electrical stimulation and ultrasonic therapy. There were 28 cases in the manipulation treatment group, including 14 males and 14 females, aged 24 to 68 years old with an average of (49.82±14.85) years old;the course of disease ranged from 3 to 14 months with an average of (9.61±3.05) months;15 cases were on the left side and 13 cases on the right side;17 cases were at the L4, 5 segment and 11 cases at the L5S1 segment. They were treated with orthopedic manipulation combined with daoyin exercises. The visual analogue scale (VAS), Oswestry disability index (ODI) and bilateral erector spinae muscle tone were compared between the two groups before treatment, after 2 weeks and 4 weeks of treatment. RESULTS: The two groups of patients were followed up and evaluated before treatment, 2 weeks and 4 weeks after treatment. The VAS of the manipulation treatment group and the traditional physical therapy group decreased from (5.46±0.99) and (5.41±1.05) points before treatment to (1.75±0.79) and (2.29±0.82) points after 4 weeks of treatment, respectively. Both groups were significantly improved after treatment compared with before treatment, and the differences were statistically significant (P<0.05);and the manipulation treatment group was better than the traditional physical therapy group at 4 weeks of treatment, with a statistically significant difference (P<0.05). The ODI of the manipulation treatment group and the traditional physical therapy group before treatment was (20.25±2.72) and (18.96±2.52) points, respectively, which decreased to (15.46±1.88) and (16.56±2.01) points after 2 weeks of treatment, and to (11.54±1.23) and (12.85±1.72) points after 4 weeks of treatment. Both groups were significantly improved after treatment compared with before treatment, and the differences were statistically significant (P<0.05), and the ODI in the manipulation treatment group was better than that in the traditional physical therapy group after treatment (P<0.05). There was no significant statistical difference in the displacement of erector spinae muscle tone between the healthy side and the affected side in both the manipulation treatment group and the traditional physical therapy group before treatment (P>0.05). After 2 weeks of treatment, the displacement values of erector spinae muscle tone on the healthy side in the manipulation treatment group and the traditional physical therapy group were (6.68±0.81) mm and (6.45±0.65) mm, respectively, and those on the affected side were (5.87±0.82) mm and (5.61±0.84) mm, respectively. After 4 weeks of treatment, the displacement values of erector spinae muscle tone on the healthy side in the manipulation treatment group and the traditional physical therapy group were (7.51±0.75) mm and (7.04±0.63) mm, respectively, and those on the affected side were (6.87±0.78) mm and (6.33±0.82) mm, respectively. The displacement values of erector spinae muscle tone on both the healthy and affected sides in both groups were significantly higher than those before treatment, and the differences were statistically significant (P<0.05);the displacement of erector spinae muscle tone in the manipulation treatment group after 4 weeks of treatment was better than that in the traditional physical therapy group, with a statistically significant difference (P<0.05). CONCLUSION Orthopedic manipulation combined with daoyin exercises can effectively improve the symptoms and lumbar function of patients with chronic lumbar disc herniation, and has more advantages in improving the tone of the erector spinae muscle.
Humans ; Male ; Female ; Middle Aged ; Adult ; Intervertebral Disc Displacement/physiopathology* ; Aged ; Lumbar Vertebrae/injuries* ; Exercise Therapy ; Chronic Disease/therapy* ; Manipulation, Orthopedic ; Combined Modality Therapy

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

This study was performed to explore the downstream mechanism of TRIB3 mediated macrophage pro-inflammatory M1 polarization under high glucose condition.RAW264.7 were divided into CON-DMSO group,CON-SC79 group,HG-DMSO group,and HG-SC79 group.Western blot was used to detect the protein expressions of TRIB3,AKT and p-AKT.Then,RAW264.7 were divided into control vector-DMSO group,TRIB3 overexpress-DMSO group,control vector-SC79 group,TRIB3 overexpress-SC79 group,control vector-MK2206 group,and TRIB3 overexpress-MK2206 group.CCK-8 was used to detect cells activity;phase contrast microscope was used to observe cell morphology;Western blot was used to detedcted the protein expressions of TRIB3,AKT,p-AKT,iNOS and Arg-1.ELISA was used to detedcted the protein secretion of IL-1β and IL-10.Data showed that TRIB3 was significantly increased and p-AKT/AKT was significantly decreased in HG group as compared with the CON group.Compared with corresponding control vector group,TRIB3 was significantly increased and p-AKT/AKT was significantly decreased in TRIB3 overexpress group.Compared with corresponding DMSO group,p-AKT/AKT was significantly increased in SC79 group,and was significantly decreased in MK2206 group.Compared with TRIB3 overexpress-DMSO group,TRIB3 overexpress-SC79 group showed significant reduction in spindle shaped and irregular shaped cells,significantly decreased iNSO and IL-1β,and significantly increased IL-10.TRIB3 overexpress-MK2206 group showed further increase in spindle and irregular shaped cells,significantly decreased Arg-1 and IL-10,and significantly increased IL-β.In conclusion,TRIB3 activated under high glucose condition exerts pro-inflammatory effect by targeting AKT phosphorylation to induce M1 polarization and inhibit M2 polarization in macrophages.

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

Objective To establish drug use evaluation(DUE)criteria for aminocaproic acid injection,and to evaluate and analyse clinical use of aminocaproic acid injection.Methods Based on the aminocaproic acid injection drug label,DUE of aminocaproic acid injection from three aspects(indications,medications and medication results)were established with reference to relevant literature.A retrospective survey was conducted to evaluate the rationality of medication for inpatients who used aminocaproic acid injection from July 1,2021 to June 30,2022 in Fuding Hospital of Fujian University of Traditional Chinese Medicine.Results A total of 143 midical records were included.73 cases fully met the DUE criteria,70 cases did not fully meet the DUE criteria,and the unreasonable rate was 48.95%.The most common types of irrational using of aminocaproic acid injection were inappropriate timing of perioperative prevention of medication(26.57%),overcourse in perioperative prevention of medication(23.08%),and contraindications(7.69%).Conclusions The aminocaproic acid injection DUE standard established is scientific,practical,the irrational rate of aminocaproic acid injection use is relatively high in this hospital,and the management of rational use of aminocaproic acid injection needs to be strengthened.

BACKGROUND: Familial hypercholesterolemia (FH) is a common autosomal dominant hereditary disease. Its early diagnosis and intervention significantly improve the patient's quality of life. However, there are few types of research on the FH pathogenic genes in China. METHODS: In this study, we recruited a family diagnosed with FH and used whole exome sequencing (WES) to analyze the proband variants. Intracellular cholesterol level, reactive oxygen species (ROS) level, and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells. RESULTS: A heterozygous missense variant predicted to be deleterious to LDLR (c.1879G > A, p.Ala627Thr) was identified in the proband. Mechanistically, intracellular cholesterol level, ROS level, and the expression of pyroptosis-related genes, nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome and components (caspase 1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and NLRP3), gasdermin D (GSDMD), interleukin (IL) -18, IL-1β was elevated in the variant LDLR group, which was attenuated by inhibition of ROS. CONCLUSIONS FH is associated with a variant (c.1879G>A, p.Ala627Thr) in the LDLR gene. Regarding the mechanism, the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Background: and Purpose Orthostatic hypotension (OH) is common in patients with Parkinson’s disease (PD). Early recognition OH is required with sensitive assessments. The purpose of this study was to determine whether blood pressure (BP) changes during exercise can predict the occurrence of OH in PD. Methods: This prospective cohort study included 80 consecutive patients with PD. All patients agreed to participate in a baseline evaluation and cardiopulmonary exercise test (CPET).According to the initial active standing test (AST), those without OH (PD-nonOH) at baseline had their AST results followed up for 6 months. The main outcome was defined as whether patients without OH at baseline would develop OH after 6 months. Logistic regression analysis was applied to identify the relevant variables. A nomogram was constructed based on clinical features and identified variables. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) were used to evaluate the accuracy and predictive ability of the nomogram, respectively. Results: CPET results indicated that peak load, peak heart rate, heart rate recovery at 1 min, and systolic BP change (ΔSBP) were lower in those with OH than in the PD-nonOH group (p<0.05) at baseline. Logistic regression analysis indicated that peak load and ΔSBP during CPET had significant effects on OH (p<0.05). Age, sex, peak load, and ΔSBP were used to construct the nomogram model (C-index=0.761). The prediction model had an AUC of 0.782 (95% confidence interval=0.649–0.889) and a specificity and sensitivity of 70.0% and 81.8%, respectively. Conclusions This study has identified predictive factors for OH development in patients with PD. CPET could be used as a complementary examination to identify patients at a high risk of OH.

Objective: To explore the efficacy and safety of transcatheter pulmonary valve perforation in the treatment of neonatal pulmonary atresia with intact ventricular septum (PA-IVS). Methods: The clinical data on surgical treatment and follow-up in 16 patients with PA-IVS who underwent transcatheter pulmonary valve perforation in Women and Children's Hospital, Qingdao University from October 2018 to October 2021 were analyzed retrospectively. The right ventricular systolic pressure and percutaneous oxygen saturation (SpO₂) were compared before and after operation. In addition, the SpO₂ and echocardiographic data at preoperative and the last follow-up were compared. Comparisons between groups were performed using paired-samples t test. Results: Among the 16 patients (10 males and 6 females) with the age at operation of 19 (14, 26) days, 12 cases underwent transcatheter pulmonary valve perforation successfully, 2 cases were transferred to surgery department for open-heart pulmonary valvulotomy, and the remaining 2 cases were transmitted to surgery department for transthoracic pulmonary valve perforation. The age at operation of the 12 patients who underwent transcatheter pulmonary valve perforation was 18 (14, 27) days, and the weight was (3.6±0.4) kg. The immediate postoperative right ventricular systolic pressure decreased significantly ((57±16) vs. (95±19) mmHg (1 mmHg=0.133 kPa), t=7.49, P<0.001), and the postoperative SpO₂ was improved effectively (0.90±0.48 vs.0.75±0.09, t=-5.61, P<0.001). The follow-up time was 22 (7, 33) months for 12 patients who underwent transcatheter pulmonary valve perforation successfully. At the last follow-up, the ratio of right to left ventricular transverse diameter was significantly higher than that before operative (0.55±0.05 vs. 0.45±0.05, t=-3.27,P=0.007). Furthermore, the Z-scores of pulmonary valvular diameter (-0.78±0.23 vs. -1.73±0.56, t=-8.52, P<0.001) and the tricuspid valvular diameter (-0.52±0.12 vs. -1.46±0.38, t=-10.40, P<0.001) were all significantly higher than preoperative data. At last, all the patients achieved biventricular circulation without death or major complications. Conclusion: Transcatheter pulmonary valve perforation is a safe and effective therapy for neonatal PA-IVS, and its curative effect has been confirmed by the medium follow-up data.
Child ; Male ; Infant, Newborn ; Humans ; Female ; Pulmonary Valve/surgery* ; Retrospective Studies ; Pulmonary Atresia/surgery* ; Heart Defects, Congenital

OBJECTIVE: To evaluate the diagnostic performances of salivary gland ultrasonography(SGUS)in Sjögren's syndrome(SS). METHODS: A total of 246 patients with dry mouth and/or eyes who were treated in the outpatient department and inpatient department of Rheumatology and Immunology Department of the Ninth People's Hospital, Shanghai Jiaotong University School of Medicine from December 2019 to January 2022 were collected. All patients received SGUS examination and scored by 2019 outcome measures in rheumatology clinical trial (OMERACT)ultrasonic scoring system.Their general information, unstimulated saliva flow rate(USFR), Schirmer test and serological test results were recorded. In the study, 193 cases had lip gland biopsy. The 2016 American College of Rheumatology(ACR)/ European League Against Rheumatism(EULAR)classification criteria were adopted as the diagnostic standard of SS. χ² test was used to compare the difference of salivary gland ultrasonic scores between the two groups. The receiver operating characteristic(ROC) curve was used to evaluate the accuracy of SGUS in diagnosing SS, and the disease characteristics of SGUS positive group and negative group in the SS patients were compared. RESULTS: A total of 175 patients were SS group according to the ACR/EULAR classification, and the remaining 71 patients were non-SS group.There was no significant difference in age [(54.2±11.8) years vs. (53.4±14.9) years, P=0.705] and female (94.4% vs.93.1%, P=1.000) between SS and non-pSS groups. A total of 109 patients were SGUS positive (≥ 2 points), of whom 104 patients met the SS diagnosis and 5 patients did not meet the SS diagnosis. The positive rate of SGUS in SS group was significantly higher than that in non-SS group (59.4% vs. 7.0%, P < 0.001). The accuracy of 2019 OMERACT ultrasonic scoring system to predict ACR/EULAR classification was good, with an area under the curve of 0.762 (95%CI 0.701-0.823). The absolute agreement between the SGUS outcome and ACR-EULAR classification was 69.1%(170/246), with a sensiti-vity of 59.4%(104/175), specificity of 93%(66/71), positive predictive value of 95.4%(104/109) and negative predictive value of 48.2% (66/137). A total of 81 patients were positive SGUS combined with anti-SSA antibody, 100% (81/81) fulfilled the ACR-EULAR criteria, 85 patients were negative SGUS and anti SSA antibody, and 60 patients(70.6%, 60/85) did not fulfil the ACR-EULAR criteria. SGUS positive group had higher antinuclear antibody(ANA) positive rate(83.1% vs. 98.1%, P < 0.001) in the patients with SS. CONCLUSION The OMERACT ultrasonic scoring system has high diagnostic value in SS. The combination of SGUS and anti-SSA antibody can improve the diagnostic value.
Humans ; Female ; Adult ; Middle Aged ; Aged ; Sjogren's Syndrome/diagnostic imaging* ; Sensitivity and Specificity ; China ; Salivary Glands/pathology* ; Ultrasonography/methods*