As a patented characteristic medicine of Yi ethnic minority， Pingxuan capsules have the effects of nourishing the liver and kidney， pacifying the liver， and subduing Yang. With the main indications of dizziness， headache， palpitations， tinnitus， insomnia， dreaminess， waist and knee soreness caused by liver-kidney deficiency and liver Yang upward disturbance， Pingxuan capsules are widely used in the treatment of posterior circulation ischemic vertigo， vestibular migraine， benign paroxysmal positional vertigo. However， the current knowledge is limited regarding the efficacy， syndrome differentiation， and safety of this medicine. On the basis of summarizing the experience of clinicians and the existing evidence， this study invites clinical experts of traditional Chinese and Western medicine， pharmaceutical experts， and methodological experts from relevant fields across China to conduct evidence-based evaluation of Pingxuan capsules. The evaluation follows the Specifications for the Development of Clinical Expert Consensus on Chinese Patent Medicines issued by the Standardization Office of the China Association of Chinese Medicine， and reaches 5 recommendations and 16 consensus suggestions. The consensus clarifies the clinical applications， efficacy， dose， course of treatment， combination of medicines， precautions， and contraindications of Pingxuan capsules in the treatment of vertigo and explains the safety of clinical application. This consensus is applicable to clinicians （traditional Chinese medicine， Western medicine， and integrated traditional Chinese and Western medicine） and pharmacists in tertiary hospitals， secondary hospitals， and community-level medical and health institutions across China， providing a reference for the rational use of Pingxuan capsules in the treatment of vertigo. It is hoped that the promotion of this consensus can facilitate the rational use of drugs in clinical practice， reduce the risk of drug use， and give full play to the advantages of Pingxuan capsules in the treatment of vertigo diseases. This consensus has been reviewed and published by the China Association of Chinese Medicine， with the number GS/CACM330-2023.

ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi， so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） combined with Smart aroma database and National Institute of Standards and Technology（NIST） database were used to characterize the aroma components in different parts of N. jatamansi， and the aroma components were quantified according to relative response factor（RRF） and three internal standards， and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis（OPLS-DA） and cluster thermal analysis based on variable importance in the projection（VIP） value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose， and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data， and the rapid identification model of different parts of N. jatamansi was established by principal component analysis（PCA）， discriminant factor alysis（DFA）， soft independent modeling of class analogies（SIMCA） and statistical quality control analysis（SQCA）. ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi， of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components， the contents of five components（ethyl isovalerate， 2-pentylfuran， benzyl alcohol， nonanal and glacial acetic acid，） in the aboveground part of N. jatamansi were significantly higher than those in the underground part（P<0.01）， the contents of β-ionone， patchouli alcohol， α-caryophyllene， linalyl butyrate， valencene， 1，8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part（P<0.01）. Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82， and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted， respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%， the validation score of the SIMCA model for discrimination of the two parts was 99， and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose（PCA， DFA， SIMCA and SQCA） can realize the rapid identification of different parts of N. jatamansi. Combining the two results， it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.

OBJECTIVES: To investigate the effect of in vitro cultured calculus bovis (ICCB) on cerebral ischemia/reperfusion injury (CIRI) and its mechanism. METHODS: A CIRI rat model and a cell model were induced by middle cerebral artery occlusion (MCAO) in Sprague Dawley rats and oxygen glucose deprivation/reperfusion (OGD/R) in BV2 cells, respectively. The CIRI rat model was evaluated using the modified neurological severity score (mNSS), brain water content, and cerebral infarction volume after 1.5 h of ischemia followed by 72 h of reperfusion. Histopathological changes in the cortex and hippocampal CA1 region were observed with hematoxylin and eosin staining. Microglial polarization and NOD-like receptor thermal protein domain associated protein (NLRP) 3 inflammasome expression in the cortex were examined by immunofluorescence. BV2 cell viability was measured via MTT assay after treatment with ICCB and Nigericin. The expressions of NLRP3, ASC, caspase-1 proteins and inflammatory cytokines were detected with Western blotting in OGD/R treated BV2 cells (0.5 h OGD+24 h reperfusion) and in cells pretreated with Nigericin for 24 h. RESULTS: ICCB treatment significantly improved neurological function, reduced cerebral infarct volume and brain water content, and mitigated pathological damage in the cortical and hippocampal CA1 regions of rats subjected to CIRI (all P<0.05). ICCB promoted the transition of cortical microglia from M1 to M2 phenotypes and suppressed NLRP3 activation in microglial cells (all P<0.01). ICCB significantly down-regulated the expression of NLRP3, ASC, and caspase-1 proteins, and reduced the secretion of IL-18 and IL-1β in BV2 cells of OGD/R model (all P<0.01). In addition, Nigericin significantly reversed the salvage effect of ICCB on model cells (both P<0.01) and the modulation of inflammatory cytokines (P<0.05). CONCLUSIONS ICCB exerts a protective effect against CIRI by mitigating neuroinflammation, through the reduction of M1 microglial polarization, promotion of M2 conversion, and suppression of the NLRP3/ASC/caspase-1 signaling pathway.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Microglia/metabolism* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein ; Brain Ischemia/metabolism* ; Male

OBJECTIVE: To investigate the effect of intraoperative blood salvage autotransfusion on local recurrence and long-term metastasis of patients after carotid body tumor resection. METHODS: We retrospectively reviewed a consecutive series of 61 patients undergoing elective carotid body tumor resection from August 2009 to December 2020. Among them, 14 received intraoperative blood salvage autotransfusion (autotrasfusion group) and 47 did not (non-autotransfusion). Data of general information, surgical status and postoperative follow-up results were collected. RESULTS: The proportion of Shamblin Ⅲ in the autotransfusion group was 85.7%, which was significantly higher than 31.9% in the non-autotransfusion group (P=0.003). The average operation time of the 14 patients in the autotransfusion group was (264±84) min, intraoperative blood loss was 1 200 (700, 2 700) mL, and autologous blood transfusion was 500 (250, 700) mL. Of these, 8 patients (57%) required concomitant allogeneic blood with 400 (260, 400) mL of allogeneic blood. The average operation time of the 47 patients in the non-autotransfusion group was (153±75) min, and the intraoperative blood loss was 300 (100, 400) mL. Of these, 6 (13%) required allogeneic blood transfusion, and 520 (400, 520) mL of allogeneic blood was used. Compared with the non-autotransfusion group, the average operation time in the autologous blood transfusion group was significantly longer (P < 0.001), and the intraoperative blood transfusion volume was larger (P=0.007). Of the 14 patients undergoing autotransfusion, 8 (57%) needed allogeneic blood at the same time; while in the 47 non-autologous transfusion patients, 6 (13%) needed allogeneic blood transfusion. The proportion of autotransfusion group using allogeneic blood at the same time was even higher (P=0.002). The incidence of nerve injury within 30 days after surgery was 29.5%, and there was no significant difference between the two groups. No early deaths occurred. The average follow-up was (76±37) months. One case of local recurrence occurred in the non-autotransfusion group. There was no distant metastasis. There were no tumor-related deaths. The estimated 5-year and 10-year overall survival rates were 96.4% and 83.8%, respectively. There was no significant difference in overall survival between the two groups (P=0.506). CONCLUSION The use of intraoperative blood salvage autotransfusion increased no risk of local recurrence and distant metastasis in patients with carotid body tumor, which is safe and effective in carotid body tumor resection.
Humans ; Blood Transfusion, Autologous/methods* ; Operative Blood Salvage/methods* ; Retrospective Studies ; Male ; Female ; Carotid Body Tumor/pathology* ; Middle Aged ; Prognosis ; Neoplasm Recurrence, Local ; Blood Loss, Surgical ; Aged ; Adult ; Operative Time

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective To analyze the medication rule of Traditional Chinese Medicine(TCM)in treating diabetes nephropathy(DN)and to explore the interaction between core components and key targets.Methods Based on the ancient and modern medical case cloud platform,the medication rules of TCMs and the drug pairs with the highest frequency in treating DN were summarized.Then the network pharmacology approach was utilized to analyze the pharmacodynamic material basis and mechanisms of the highest frequency-drug pairs.The potential targets were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)databases.TTD,DISGENET,and GENECARD databases were used to obtain the related targets of DN and screen out the potential targets for DN.In order to clarify the relationships between the active ingredients,the core targets,and pathways,STRING and Cytoscape 3.7.1 software were used to construct the protein-protein interaction(PPI)network and core drugs-ingredients-targets-disease interaction network,DAVID database was screened for Kyoto Encyclopedia of Genes and Gnomes(KEGG)enrichment analysis of core targets.Sybyl 2.1 software and biofilm interference verify the combined capacity between the core ingredients and key targets.Results Among 183 prescriptions,Astragali Radix had the highest use frequency and average dose,43 times and 37 g,respectively,followed by Salviae miltiorrhizae Radix and Poria cocos.To find the core combined with the highest confidence in association analysis was astragalus,salvia miltiorrhiza,and tuckahoe.Correlation analysis indicates that the core combination with the highest confidence was Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos.Network pharmacologic showed 89 potential targets and 15 key signaling pathways for the treatment of DN by the drug pair.TNF signaling pathway,Nod-like receptor signaling pathway,and MAPK signaling pathway were disease-related pathways,and IL-6,TNF,and vascular endothelial growth factor A(VEGFA)were core targets.Isorhamnetin and quercetin of the drug pair had high binding ability with IL6,the scores were 8.2 and 7.4,respectively,and the dissociation constants(KD)were 5.6×10-5 mol·L-1 and 6.8×10-5 mol·L-1,respectively.Conclusion This study preliminarily finds the prescription rule of treating DN with Astragali Radix-Salviae miltiorrhizae Radix-Poria cocos as the core drug pair,isorhamnetin,and quercetin are probably the main active compounds of this drug pair in DN treatment,which provides a basis for clinical treatment and drug discovery of DN.

Objective:To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China.Methods:The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia.Results:The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% ( HR=1.22, 95% CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% ( HR=0.67, 95% CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion:Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

BACKGROUND:Compound Shengmai Chenggu capsule has good therapeutic effects on early steroid-induced osteonecrosis of the femoral head,but the exact mechanism of treatment is not fully understood. OBJECTIVE:To observe the effect of compound Shengmai Chenggu capsule on fucosyltransferase 8,osteogenic gene and Wnt/β-catenin in bone tissue of rats with steroid-induced osteonecrosis of the femoral head. METHODS:Sixty Sprague-Dawley rats were randomized into blank group,model group,low-,middle-,and high-dose drug groups(n=12 per group).In the latter four groups,animal models of steroid-induced osteonecrosis of the femoral head were established by subcutaneous injection of imiquimod(once every 2 weeks,2 times in total)and gluteal muscle injection of methylprednisolone(once a week,4 times in total).The low-,middle-and high-dose drug groups were given 1.89,3.78 and 7.56 g/kg per day compound Shengmai Chenggu capsule solution by gavage respectively on the second day after the last modeling.The same amount of saline was given by gavage to the model group.Administration lasted 8 weeks.After the administration,micro-CT scan,histological staining,compression test,RT-qPCR and western blot were performed on the femoral head. RESULTS AND CONCLUSION:Micro-CT scan results showed that compared with the blank group,trabecular volume fraction,trabecular number and trabecular thickness were significantly decreased(P<0.05),while trabecular separation was increased in the model group(P<0.05).Compared with the model group,the compound Shengmai Chenggu capsule could increase trabecular volume fraction,trabecular number and trabecular thickness(P<0.05),and decrease trabecular separation(P<0.05)in a dose-dependent manner.Hematoxylin-eosin staining results showed that compared with the model group,the rate of empty bone lacunae was reduced in a dose-dependent group in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups(P<0.05).Immunohistochemical staining results showed that compared with the blank group,the protein expression of fucosyltransferase 8,Runx2 and bone morphogenetic protein 2 was reduced in the model group(P<0.05);compared with the model group,the compound Shengmai Chenggu capsule increased the protein expression of fucosyltransferase 8,Runx2 and bone morphogenetic protein 2 in a dose-dependent manner(P<0.05).Results from the compression test showed that there was a dose-dependent increase in the maximum load and elastic modulus of the femoral head in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups compared with the model group(P<0.05).RT-qPCR and western blot results showed that the mRNA and protein expressions of fucosyltransferase 8,Runx2,alkaline phosphatase,osteocalcin,osteoblast-specific transcription factor and bone morphogenetic protein 2 were decreased in the model group compared with the blank group(P<0.05);compared with the model group,there was a dose-dependent increase in the mRNA and protein expressions of the above indicators in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups compared with the model group(P<0.05).Compared with the blank group,the mRNA and protein expression of Wnt2,low-density lipoprotein receptor-related protein 5 and β-catenin were decreased(P<0.05)and the mRNA and protein expressions of glycogen synthase kinase 3β were increased(P<0.05)in the model group;compared with the model group,there was a dose-dependent increase in the mRNA and protein expressions of Wnt2,low-density lipoprotein receptor-related protein 5 and β-catenin(P<0.05)but a dose-dependent decrease in the mRNA and protein expressions of lycogen synthase kinase 3β(P<0.05)in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups.To conclude,the mechanism by which the compound Shengmai Chenggu capsule treats steroid-induced osteonecrosis of the femoral head may activate the Wnt/β-catenin signaling pathway through the up-regulation of fucosyltransferase 8,thereby promoting bone formation.

BACKGROUND:The majority of studies on developmental dysplasia of the hip focus on hip malformations,but there are few reports on the effects of acetabular dysplasia on the spine. OBJECTIVE:To investigate the compensation of spinopelvic parameters in coronal and sagittal views in patients with developmental dysplasia of the hip,and to explore the correlation between acetabular development and spinopelvic parameters. METHODS:A total of 101 patients with developmental dysplasia of the hip admitted to the Third Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2018 to June 2022 were selected as the trial group,and 114 healthy subjects were selected as the control group during the same period.The spinopelvic parameters of the subjects were measured through the full-length X-ray films of the coronal and sagittal spines:lumbar lordosis,anterior pelvic tilt,thoracolumbar kyphosis,Cobb angle,and the distance between the C7 plumb line and the center sacral vertical line,sacral slope,pelvic incidence,and thoracic kyphosis.The differences in spinopelvic parameters were compared between the two groups.In addition,the differences in spinopelvic parameters in patients with unilateral,bilateral and different Crowe classifications of developmental dysplasia of the hip were compared.Pearson correlation analysis was used to explore the correlation between Sharp angle and spinopelvic parameters. RESULTS AND CONCLUSION:(1)In the sagittal view,the lumbar lordosis in the trial group was significantly lower than that in the control group(P<0.05).The pelvic tilt and kyphosis angle of the thoracolumbar segment in the trial group were significantly greater than those in the control group(P<0.05).In the coronary position,the Cobb angle and the distance between the C7 plumb line and center sacral vertical line in the trial group were significantly greater than those in the control group(P<0.05).There was no significant difference in the remaining spinopelvic parameters between the two groups(P>0.05).(2)The lumbar lordosis of patients with bilateral developmental dysplasia of the hip was significantly lower than that of patients with unilateral developmental dysplasia of the hip(P<0.05).The pelvic tilt,thoracolumbar kyphosis,Cobb angle and the distance between the C7 plumb line and center sacral vertical line in bilateral developmental dysplasia of the hip patients were significantly greater than those in unilateral developmental dysplasia of the hip patients(P<0.05).(3)The lumbar lordosis decreased with the increase of Crowe classification severity(P<0.05).The pelvic tilt increased with the severity of the Crowe classification(P<0.05).(4)Pearson correlation analysis showed that Sharp angle was negatively correlated with lumbar lordosis(P<0.05),while Sharp angle was positively correlated with anterior pelvic tilt,Cobb angle,C7 plumb line and center sacral vertical line(P<0.05).(5)It is concluded that the pelvic tilt,thoracolumbar kyphosis,Cobb angle and the distance between the C7 plumb line and center sacral vertical line increase,while lumbar lordosis decreases in developmental dysplasia of the hip patients.The degree of acetabular dysplasia was significantly correlated with lumbar lordosis,pelvic tilt,Cobb angle,C7 plumb line and center sacral vertical line.

Objective:To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China.Methods:Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model.Results:The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m 2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m 2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI ( Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference ( Plinear<0.001), hip circumference ( Plinear<0.001), and calf circumference ( Plinear<0.001). Conclusion:Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.