OBJECTIVE To investigate the reference range of steady-state trough concentrations in depression patients taking paroxetine. METHODS Therapeutic drug monitoring data of 890 depression inpatients treated with paroxetine in our hospital from January 1， 2023 to December 31， 2024 were retrospectively collected. Univariate analysis and multiple linear regression analysis were employed to explore the influencing factors of the steady-state trough concentration of paroxetine， as well as the correlation between concentration and efficacy and adverse reactions. The reference range of steady-state trough concentration was obtained by receiver operating characteristic（ROC） curve method. RESULTS Patients with a greater degree of improvement in therapeutic efficacy exhibited higher steady-state trough concentrations of paroxetine （P＜0.000 1）. The steady-state trough concentrations of paroxetine and the ratio of paroxetine steady-state trough concentration to dose （C/D ratio） were significantly lower in male patients and those weighing 60-80 kg compared to female patients and those weighing＜60 kg， respectively （P＜0.05 or P＜0.000 1）. The steady-state trough concentration， C/D ratio， dosage， and concomitant medication all showed a positive correlation with therapeutic efficacy （P＜0.05 or P＜0.000 1）. Both the steady-state trough concentration and C/D ratio were correlated with liver function impairment， and the C/D ratio was also correlated with urinary retention （P＜0.05 or P＜0.000 1）. The critical threshold for the effective concentration of paroxetine was 56.31 ng/mL in the overall population， 56.42 ng/mL in males， 44.91 ng/mL in females， and 198.90 ng/mL in patients experiencing adverse reactions. CONCLUSIONS The reference range for the steady-state trough concentration of paroxetine in the overall population is 56.31-198.90 ng/mL； for male patients， it is 56.42-198.90 ng/mL， and for female patients， it is 44.91-198.90 ng/mL. Dosage of paroxetine should be reduced as appropriate for female patients and patients with low body weight or abnormal liver function.

OBJECTIVE: To investigate the biomechanical characteristics of retrograde tibial nailing (RTN) and distal tibial L-shaped plating in the internal fixation of distal tibial fractures. METHODS: Fourteen fresh adult tibia specimens were selected, comprising 7 males and 7 females aged from 34 to 55 years old. The specimens were randomly divided into experimental group and control group by numerical table method with 7 specimens in each group. RTN was used for internal fixation of distal tibial fractures in the experimental group, and L-shaped plate was used for internal fixation of distal tibial fractures in the control group. The axial compression properties of the two groups of specimens were tested under the pressure of 100, 200, 300, 400, and 500 N after operation, and torsional resistance at torque levels of 1.0, 2.0, 3.0, 4.0, 5.0 N·m. The anti-fatigue performance of the specimens was tested at 500 N pressure for 3 000 and 10 000 cycles. X-ray fluoroscopy was performed to observe whether the the internal fixator was deformed and whether the screw was loosened or broken. RESULTS: When the pressure was 400 N and 500 N, the axial compression displacement of the experimental group was (1.11±0.06) mm and (1.24±0.05) mm, which were smaller than those of the control group (1.21±0.08) mm and (1.37±0.11) mm, and the differences were statistically signific (P<0.05). Under the pressure of 500 N, the axial compression stiffness of the experimental group was (389.24±17.79) N·mm^-1, which was significantly higher than that of the control group (362.37±14.44) N·mm^-1(P<0.05). When the torque was 4 and 5 N·m, the torsion angles of the experimental group were (2.97±0.23) ° and (3.41±0.17) °, which were smaller than those of the control group (3.31±0.28) ° and (3.76±0.20) °, and the differences were statistically significant (P<0.05). When the torque was 5 N·m, the torsional stiffness of the experimental group was (1.48±0.07) N·m per degree, which was higher than that of the control group (1.36±0.06) N·m per degree, and the difference was statistically significant (P<0.05). For the intragroup comparison of fatigue resistance, the differences in axial compression displacement between the two groups were not statistically significant at 3 000 and 10 000 cycles (all P>0.05). When 3 000 times and 10 000 times of compression, the axial compression displacement of the experimental group was (1.38±0.08), (1.43±0.07) mm, which was smaller than that of the control group (1.51±0.10), (1.54±0.08) mm, the differences were statistically significant (P<0.05). In the experimental group, no screw loosening, fracture or internal fixation deformation was found, while in the control group, locking screw loosening occurred in 2 models after 10 000 pressures. CONCLUSION The biomechanical performance of RTN is obviously better than that of the distal tibial L-shaped plate, which provides biomechanical data support for the clinical application of RTN.
Humans ; Female ; Male ; Adult ; Tibial Fractures/physiopathology* ; Middle Aged ; Biomechanical Phenomena ; Bone Plates ; Fracture Fixation, Internal/instrumentation* ; Bone Nails ; Tibia/surgery*

OBJECTIVE To investigate the expression and clinical significance of Periostin in tissues of patients with chronic rhinosinusitis(CRS).METHODS Real-time quantitative PCR and immunohistochemistry were used to detect periostin expression in eosinophilic CRS with nasal polyps(ECRSwNP),non-eosinophilic CRS with nasal polyps(non-ECRSwNP),CRS without nasal polyps(CRSsNP),and control tissues.Correlations between periostin levels and blood eosinophil percentage(Eos%),Lund-Mackay score,modified endoscopic score,and Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis(JESREC)score were analyzed.Additionally,changes in SNOT-22 and VAS scores were compared at different preoperative and postoperative times.The predictive value of periostin for ECRSwNP was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Periostin expression was detected in all groups(ECRSwNP,non-ECRSwNP,CRSsNP,and controls),with predominant localization in the basement membrane and mucosal subepithelial lamina propria.Significantly elevated periostin levels were detected in the ECRSwNP group compared to the other three groups(P<0.001).Furthermore,Periostin mRNA expression showed significant positive correlations with blood Eos%,JESREC score,and Lund-Mackay score.SNOT-22 and VAS scores were significantly elevated in the ECRSwNP group at preoperative evaluation and 9 months postoperatively(P<0.001).ROC curve analysis demonstrated that periostin had a substantial predictive value for ECRSwNP(AUC=0.957).CONCLUSION Periostin plays a crucial role in the pathogenesis of chronic rhinosinusitis,contributing to the diagnosis,severity assessment,and prognosis evaluation of ECRSwNP,while offering potential therapeutic targets for CRS management.

OBJECTIVE To compare the expression characteristics of transforming growth factor-β1(TGF-β1),Smad2,Smad3,and epithelial-mesenchymal transition(EMT)-related markers(E-cadherin,N-cadherin,vimentin)in patients with different types of chronic sinusitis(CRS),to analyze the correlations of E-cadherin,N-cadherin and vimentin with TGF-β1 and the prognosis of surgical treatment in patients with different types of CRS.METHODS The expressions of E-cadherin,N-cadherin,vimentin,TGF-β1,Smad2 and Smad3 in patients with different types of CRS and the control group were compared by Western blotting(WB)and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Analyze its correlation with the improvement degree of each clinical score after the operation.RESULTS Compared with the control group,the expression of E-cadherin decreased in the CRSsNP group,the non-ECRSwNP group and the ECRSwNP group,while the expressions of vimentin and N-cadherin increased.The protein expression of TGF-β1 in the CRSsNP group was higher than that in the non-ECRSwNP group and the control group(P<0.001),and the expressions of Smad2 and Smad3 in the CRSsNP group were higher than those in the ECRSwNP group,the non-ECRSwNP group and the control group(P<0.001).In the CRSsNP group,there was a positive correlation between TGF-β1 and vimentin(r=0.675,P=0.011),and a negative correlation with E-cadherin(r=-0.802,P=0.001).The expression of E-cadherin was negatively correlated with the improvement amplitude of SNOT-22 nasal symptom scores in patients with different types of CRS(P<0.05).CONCLUSION The EMT phenomenon occurs in different types of CRS.In CRS SNPS,EMT may be related to the TGF-β1/Smad signaling pathway.The expressions of EMT markers E-cadherin,N-cadherin and vimentin are correlated with the decrease in the severity of postoperative disease in patients with CRS,suggesting a potential association between the EMT process and the surgical prognosis of patients with CRS.

ObjectiveThe antitumor activity of sesquiterpenoid M36 isolated from Myrrha against human hepatoma HepG2 cells was investigated in this study. MethodHepG2 cells were treated with M36 at different concentrations （0， 2， 4， 6， 8， 10 μmol·L^-1）. Firstly， the effects of M36 on the proliferation of human hepatoma HepG2 cells were detected by methyl thiazolyl tetrazolium （MTT）， colony formation assay， and EdU proliferation assay. Hoechst staining， flow cytometry analysis， and Western blot were used to explore the effect of M36 on the apoptosis of human hepatoma HepG2 cells. Acridine orange staining and western blotting were used to examine the effect of M36 on autophagy in HepG2 cells. Finally， Western blot was used to detect protein expression of cancer-related signaling pathways. ResultCompared with the blank group， M36 treatment significantly inhibited the proliferation of human hepatoma HepG2 cells （P<0.01）， and the half inhibitory concentration （IC₅₀） value of M36 for 48 h was 5.03 μmol·L^-1， in a dose- and time-dependent manner. M36 was also able to induce apoptosis and autophagy in human hepatoma HepG2 cells. After treatment with 8 μmol·L^-1 M36 for 48 hours， the apoptosis rate of HepG2 cells was （42.03±9.65）% （P<0.01）. Compared with the blank group， HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h had a significant increase in cleaved poly ADP-ribose polymerase （cleaved-PARP） protein levels （P<0.01）. Acridine orange staining showed that autophagy was significantly activated in HepG2 cells treated with 4 and 8 μmol·L^-1 M36 for 48 h compared with the blank group （P<0.01）， which was further verified by the up-regulation of microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. Western blot results showed that compared with the blank group， the levels of phosphorylated extracellular regulated protein kinase （p-ERK）， phosphorylated p38 mitogen-activated protein kinase （p-p38 MAPK）， phosphorylated c-Jun N-terminal kinase （p-JNK）， and its downstream nuclear transcription factors c-Jun and p-c-Jun protein were significantly increased in M36 group （P<0.05， P<0.01）. The mechanism may be related to the up-regulation of MAPK signaling pathway. ConclusionThe sesquiterpenoid M36 isolated from Myrrha inhibits the proliferation of human hepatoma HepG2 cells and promotes apoptosis and autophagy， which may be related to the activation of the MAPK signaling pathway.

Objective To establish the energy expenditure(EE)prediction models of health Qigong Wuqinxi based on heart rate combined with accelerometer counts in different body parts,so to provide a reference for monitoring EE of Wuqinxi.Methods Seventy-four healthy college students aged 18-30 were selected as the research objects.They were divided into a skilled group of 39(21 males and 18 females)and a primary group of 35(17 males and 18 females)according to their level of practice,with 55 in the model group and 19 in the validation group.When performing a set of Wuqinxi,all subjects were recorded heart rate(HR),accelerometer counts[the average counts of X-axis,Y-axis,Z-axis and vector magnitude(VM)],and EE-related indicators by wearing the Polar heart rate moni-tor,ActiGraph-GT3X+accelerometers(9 parts:waist,both arms,both wrists,both thighs,and both ankles)and CORTEX Meta Max3B-R2 portable indirect calorimeter.Based on the accurate EE mea-sured by the gas metabolism meter,linear regression models of only HR,only accelerometer counts,or HR combined accelerometer counts were established,and their accuracy was analyzed and com-pared.Results The EE of Wuqinxi was significantly correlated with gender,height,weight,muscle mass,HR-related indicators,and accelerometer counts in different parts(X-axis counts of the waist,VM values of the left thigh and counts of the X-axis and Y-axis,VM values of the right thigh and the Y-axis,Z-axis count value,left ankle VM value and Y-axis count value,right ankle VM value and Y-axis,Z-axis count value)(P<0.05).Moreover,the adjusted R2 of the prediction model of only HR,only accelerometer counts,and the both were 0.582,0.508 and 0.678,respectively(P<0.05).The correlation between the predicted and measured values ranged between 0.706 and 0.817.Accord-ing to the Bland-Altman analysis,for each model,all except one error value fell outside the 95%confidence interval.That is,all models had an excellent fitting effect and high accuracy.Among them,the combined model was of the best prediction effect:EE(kcal)=-20.089+0.279×body weight(kg)+0.243×ΔHR(exercise HR-quiet HR,bpm)+0.001×Right thigh Y-axis count value+0.181×exer-cise HR(bpm)-4.202×gender(male=0,female=1).Conclusion The EE prediction model of Wuqinxi es-tablished on HR combined with accelerometer counts has the best effect and can calculate the EE more accurately.

Objective: Schizophrenia is a common mental disorder, and mitochondrial function represents a potential therapeutic target for psychiatric diseases. The role of mitochondrial metabolism-related genes (MRGs) in the diagnosis of schizophrenia remains unknown. This study aimed to identify candidate genes that may influence the diagnosis and treatment of schizophrenia based on MRGs. Methods: Three schizophrenia datasets were obtained from the Gene Expression Omnibus database. MRGs were collected from relevant literature. The differentially expressed genes between normal samples and schizophrenia samples were screened using the limma package. Venn analysis was performed to identify differentially expressed MRGs (DEMRGs) in schizophrenia. Based on the STRING database, hub genes in DEMRGs were identified using the MCODE algorithm in Cytoscape. A diagnostic model containing hub genes was constructed using LASSO regression and logistic regression analysis. The relationship between hub genes and drug sensitivity was explored using the DSigDB database. An interaction network between miRNA-transcription factor (TF)-hub genes was created using the Network-Analyst website. Results: A total of 1,234 MRGs, 172 DEMRGs, and 6 hub genes with good diagnostic performance were identified. Ten potential candidate drugs (rifampicin, fulvestrant, pentadecafluorooctanoic acid, etc.) were selected. Thirty-four miRNAs targeting genes in the diagnostic model (ANGPTL4, CPT2, GLUD1, MED1, and MED20), as well as 137 TFs, were identified. Conclusion Six potential candidate genes showed promising diagnostic significance. rifampicin, fulvestrant, and pentadecafluorooctanoic acid were potential drugs for future research in the treatment of schizophrenia. These findings provided valuable evidence for the understanding of schizophrenia pathogenesis, diagnosis, and drug treatment.

This work aims to explore the effect of glycolysis on the replication of porcine reproductive and respiratory syndrome virus (PRRSV) in porcine alveolar macrophages (PAMs). The changes of glucose metabolism, PRRSV protein levels, PRRSV titers, and the relative expression levels of genes and proteins in PAMs were analyzed by ELISA, qPCR, virus titration, and Western blotting after PRRSV infection. The effect of hypoxia-inducible factor-1α (HIF-1α) on PRRSV replication was subsequently assessed by specific siRNAs targeting to HIF-1α. The results showed that PRRSV infection enhanced glycolysis, elevated the levels of glucose uptake and lactate in the supernatant (P<0.05 and 0.01, respectively), reduced ATP production (P<0.05), and up-regulated the expression of hexokinase 2 (HK2), 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), and pyruvate kinase isozyme type M2 (PKM2) in PAMs (P<0.05 and 0.01, respectively). Glycolysis inhibitors down-regulated the expression of PRRSV proteins and reduced virus titers (P<0.01). The knockdown of HIF-1α by siRNAs inhibited glycolysis and lowered PRRSV titers (P<0.05). In addition, the interferon pathways inhibited by PRRSV infection were reversed by the inhibition of glycolysis. These findings may facilitate further investigation of the role of glycolysis in PRRSV replication.
Porcine respiratory and reproductive syndrome virus/physiology* ; Glycolysis ; Swine ; Animals ; Virus Replication ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Macrophages, Alveolar/metabolism* ; Porcine Reproductive and Respiratory Syndrome/virology* ; Cells, Cultured ; RNA, Small Interfering/genetics*

The prevalence and mortality of cancer have been on the rise， and it has been the global leading cause of death. The causes of cancer are diverse， such as heredity， radiation， and carcinogens. The abnormality of cell cycle regulation is also one of the causes. Cell cycle is a complex sequence of events through which a cell duplicates its contents and divides. Cell cycle is highly organized to ensure the integrity of genetic material. This process involves many regulatory genes and proteins. Cell cycle will be dysregulated when these proteins and genes change， resulting in the loss of control of cell proliferation， the inhibition of apoptosis， and finally the occurrence of tumor. At the moment， the therapies for cancer include traditional surgical resection， radiotherapy， chemical therapy， and targeted therapy. Chinese medicine has a wide range of sources and little side effect， which is worthy of further research and development. More and more studies have revealed that a variety of Chinese medicines play an anti-tumor role by inducing cell cycle arrest， so as to improve the quality of life and prolong the survival time of patients with advanced tumors. This article first introduces the characteristics and related regulatory factors of each phase of cell cycle， and enumerates the clinical and experimental examples of tumorigenesis caused by abnormal cell cycle. Then， we summarize the hot anti-tumor drugs targeting cell cycle in China and abroad， such as Cyclin-dependent kinase （CDK） inhibitors， cell division cycle 25 （CDC25） inhibitors， ataxia-telangiectasia-mutated-and-Rad3-related kinase （ATR） inhibitors， and checkpoint kinase 1 （CHK1） inhibitors. Finally， this article summarizes the recent research on the anti-tumor effect of Chinese medicine by inducing cell cycle arrest from the three aspects of cell cycle G₀/G₁ phase， S phase and G₂/M phase， in order to provide some reference for the research on the anti-tumor effect of Chinese medicine.

Vestibular migraine and patent foramen ovale are closely related conditions with linked incidence rates.This systematic review presents the potential pathophysiological mechanisms underlying the association of patent foramen ovale with vestibular migraine，delves into the clinical features and classifications of vestibular migraine as well as the shunt status and anatomical features of patent foramen ovale，and also discusses the outcome of vestibular migraine following a patent foramen ovale closure.Vasoactive peptide，microemboli，inflammation，and genetic theories have been proposed for the association of the two conditions.Although most studies support a link between vestibular migraine and patent foramen ovale，evidence is lacking to prove that patients with vestibular migraine can gain significant benefits from a patent foramen ovale closure，and moreover，the surgery-related serious adverse events and risks，such as atrial fibrillation and new-onset headache，need careful consideration.