ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

OBJECTIVE: To study the relevant factors affecting the occurrence of adjacent vertebral fractures in women with osteoporotic vertebral compression fractures after conservative treatments. METHODS: A total of 98 elderly female patients diagnosed with osteoporotic vertebral compression fractures and treated from January 2020 to January 2022 were retrospectively analyzed. The average age was (73.05±7.38) years old. Based on the follow-up results after two years of injury, the patients were divided into the adjacent vertebral fracture group (24 cases) and the non-adjacent vertebral fracture group (74 cases). The following factors were recorded for each patient:age, initial bone density, follow-up bone density, bone density changes, initial VAS score, degree of fracture compression, presence of old fractures, use of zoledronic acid, use of parathyroid hormone analogs, occurrence of complications, and further compression of the affected vertebrae. Univariate and multivariate Logistic regression analyses were performed to analyze the associated risk factors. RESULTS: Univariate analysis revealed that in elderly women undergoing conservative treatment for osteoporotic vertebral compression fractures, the degree of fracture compression, follow-up bone density, changes in bone density, use of zoledronic acid, and use of parathyroid hormone analogs were statistically significant(P<0.05). Multivariate Logistic regression analysis demonstrated that the degree of fracture compression 95%CI(0.040, 0.571), P=0.005, OR=0.151, changes in bone density 95%CI(1.264, 1 360.732), P=0.036, OR=41.477, and use of parathyroid hormone analogs 95%CI(1.638, 31.625), P=0.009, OR=7.196 were risk factors affecting the occurrence of adjacent vertebral fractures following vertebral compression fractures in elderly women with osteoporosis. CONCLUSION The degree of fracture compression, changes in bone density, and the use of parathyroid hormone analogs are factors influencing the occurrence of adjacent vertebral fractures following vertebral compression fractures in elderly women with osteoporosis. For patients with mild compression fractures (gradeⅠ), conservative treatment can be achieved by intensifying anti-osteoporosis therapy and using parathyroid hormone analogs.
Humans ; Female ; Aged ; Fractures, Compression/etiology* ; Spinal Fractures/therapy* ; Osteoporotic Fractures/therapy* ; Retrospective Studies ; Risk Factors ; Conservative Treatment ; Aged, 80 and over ; Bone Density

OBJECTIVE: To explore the role of reactive oxygen species (ROS) and lactate dehydrogenase isoenzyme X (LDH-X) in the changes of sperm mitochondrial membrane potential (MMP) in infertility patients with varicocele (VC). METHODS: This study included 38 infertility patients with VC (VCinf), 35 non-VC infertile males (NVCinf), and 30 normal fertile men as controls. We obtained the routine semen parameters using the sperm quality analysis system, examined the contents of LDH-X in the seminal plasma and sperm with the automatic biochemical analyzer, measured the level of malondialdehyde (MDA) in seminal plasma by thiobarbituric acid (TBA) colorimetry, and determined the expressions of mitochondrial membrane potential (MMP) and LDH-X mRNA in the sperm using JC-1 fluorescence probe and RT-PCR. RESULTS: No statistically significant differences were observed among the three groups of subjects in age, semen pH value, semen volume and sperm concentration (P > 0.05). Compared with the normal fertile controls, the patients in the VCinf and NVCinf groups showed significantly decreased sperm motility (［52.36 ± 12.48］% vs ［34.74 ± 15.23］% vs ［25.76 ± 13.73］%, P< 0.05), percentage of progressively motile sperm (PMS) (［42.54 ± 13.58］% vs ［29.10 ± 14.17］% vs ［20.95 ± 12.33］%, P< 0.05), sperm LDH-X (［16.46 ± 5.47］ vs ［13.63 ± 4.50］ vs ［10.18 ± 3.00］ mU/106, P< 0.05), sperm MMP (［48.04 ± 11.62］% vs ［40.86 ± 12.69］% vs ［34.41 ± 13.93］%, P< 0.05) and expression of sperm LDH-X mRNA (P< 0.05). but increased seminal plasma LDH-X (［935.36 ± 229.48］ vs ［1241.05 ± 337.07］ vs ［1425.08 ± 469.35］ U/L, P< 0.05), seminal plasma/whole sperm LDH-X (［1.06 ± 0.35］ vs ［1.40 ± 0.34］ vs ［1.63 ± 0.66］, P< 0.05), and content of seminal plasma MDA (［1.10 ± 0.19］ vs ［1.59 ± 0.27］ vs ［2.00 ± 0.22］ nmol/ml, P< 0.05). CONCLUSION Excessive ROS in the reproductive system of VCinf patients reduces the content of MMP and causes the overflow of LDH-X out of sperm cells. Therefore the decrease of sperm LDH-X may be accompanied by that of MMP.
Humans ; Male ; Infertility, Male/etiology* ; Varicocele/metabolism* ; Adult ; Reactive Oxygen Species/metabolism* ; Spermatozoa/metabolism* ; L-Lactate Dehydrogenase/metabolism* ; Membrane Potential, Mitochondrial ; Isoenzymes/metabolism* ; Case-Control Studies ; Young Adult ; Mitochondrial Membranes/metabolism*

OBJECTIVE: To explore and verify the effect and potential mechanism of Brucea javanica Seed Oil Emulsion Injection (YDZI) and Shengmai Injection (SMI) on peripheral microcirculation dysfunction in treatment of gastric cancer (GC). METHODS: The potential mechanisms of YDZI and SMI were explored through network pharmacology and verified by cellular and clinical experiments. Human microvascular endothelial cells (HMECs) were cultured for quantitative real-time polymerase chain reaction, Western blot analysis, and human umbilical vein endothelial cells (HUVECs) were cultured for tube formation assay. Twenty healthy volunteers and 97 patients with GC were enrolled. Patients were divided into surgical resection, surgical resection with chemotherapy, and surgical resection with chemotherapy combining YDZI and SMI groups. Forearm skin blood perfusion was measured and recorded by laser speckle contrast imaging coupled with post-occlusive reactive hyperemia. Cutaneous vascular conductance and microvascular reactivity parameters were calculated and compared across the groups. RESULTS: After network pharmacology analysis, 4 ingredients, 82 active compounds, and 92 related genes in YDZI and SMI were screened out. β-Sitosterol, an active ingredient and intersection compound of YDZI and SMI, upregulated the expression of vascular endothelial growth factor A (VEGFA) and prostaglandin-endoperoxide synthase 2 (PTGS2, P<0.01), downregulated the expression of caspase 9 (CASP9) and estrogen receptor 1 (ESR1, P<0.01) in HMECs under oxaliplatin stimulation, and promoted tube formation through VEGFA. Chemotherapy significantly impaired the microvascular reactivity in GC patients, whereas YDZI and SMI ameliorated this injury (P<0.05 or P<0.01). CONCLUSIONS YDZI and SMI ameliorated peripheral microvascular reactivity in GC patients. β-Sitosterol may improve peripheral microcirculation by regulating VEGFA, PTGS2, ESR1, and CASP9.
Humans ; Microcirculation/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Stomach Neoplasms/physiopathology* ; Emulsions ; Male ; Plant Oils/administration & dosage* ; Brucea/chemistry* ; Middle Aged ; Female ; Drug Combinations ; Human Umbilical Vein Endothelial Cells/metabolism* ; Seeds/chemistry* ; Injections ; Vascular Endothelial Growth Factor A/metabolism* ; Aged ; Network Pharmacology

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

[Objective] To analyze the influence of the cycle length of hepatitis B surface antigen (HBsAg) double reagent positive samples collected from voluntary blood donors in Guangzhou on the detection results. [Methods] A total of 127 044 blood samples from voluntary blood donors at Guangzhou Blood Center from August 10 to December 9, 2023 were selected. Two ELISA reagents were used for HBsAg detection, and samples with HBsAg double reagent positive and S/CO values<10 were tested continuously for 7 days to observe the changes in their S/CO values. [Results] A total of 505 HBsAg double reagent positive samples were detected, of which 52 had S/CO values less than 10. After 7 consecutive days of uninterrupted testing, the S/CO values of Wantai (median 5 decreased to 3) and Xinchuang (median 5 decreased to 3) showed an overall downward trend, and the HBsAg missed detection rate showed an upward trend (from 0 on the first day to 1/10 000 on the seventh day). A total of 13 cases had negative double reagent test results within the 7-day testing cycle. [Conclusion] With the extension of the detection cycle, the S/CO value of HBsAg detection shows a downward trend, and the missed detection rate of HBsAg shows an upward trend. Samples used for HBsAg detection should be tested promptly after sampling to improve the quality of blood testing.

Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)％,0,(42.80±6.70)％,(11.74±1.79)％;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)％,(0.5±0.15)％,(38.6±2.39)％,(1.58±0.54)％.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P＜0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P＜0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

Purpose::To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.Methods::A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1, Q 3) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy. Results::Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass ( p = 0.001), total body water (TBW, p=0.006), extracellular water ( p=0.020) and intracellular water ( p=0.010) as well as a larger ratio of basal metabolic rate/total weight ( p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat ( p=0.001) and body fat mass index ( p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% ( p=0.050, odds ratio =3.114) and 3rd space water > 0.95% ( p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries. Conclusion::TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.