OBJECTIVE To explore clinical characteristics and risk factors of drug-induced hypofibrinogenemia， providing a reference for rational clinical drug use. METHODS Retrospective case analyses literature on drug-induced hypofibrinogenemia were collected from domestic and international databases from their inception to December 31， 2024. The patients’ gender， age， fibrinogen （FIB） levels before and after treatment， drug types， the incidence of drug-induced hypofibrinogenemia， time of occurrence， bleeding rates， clinical manifestations， risk factors， and protective factors were all analyzed. RESULTS A total of 40 retrospective case analysis studies were included， involving 17 313 patients. Patient age ranged from 0.83 to 78.40 years， with males accounting for 16.90%-81.00%. The involved drugs comprised 5 categories and 13 specific agents， including tigecycline， snake venom hemocoagulase， tocilizumab， and alteplase， etc. The incidence of drug-induced hypofibrinogenemia ranged from 0 to 100%， occurring between 2 hours and 9 months after drug administration， and FIB levels rebounded in most patients after drug discontinuation. The bleeding rate varied from 0% to 91.30%， including epistaxis， airway bleeding， gastrointestinal bleeding， and cerebral hemorrhage. Risk factors included high drug dosage， prolonged treatment duration， abdominal infection， advanced age， and low baseline FIB levels. Protective factors were only mentioned in studies on tigecycline， including skin and soft tissue infections and high baseline FIB levels. CONCLUSIONS Drug-induced hypofibrinogenemia is commonly associated with tigecycline， hemocoagulase， and tocilizumab. Its clinical features vary depending on the drug， and risk factors include high drug dosage， prolonged treatment， low baseline FIB levels， and advanced age. For high-risk medications， individualized medication management and monitoring of FIB levels are recommended.

Mitochondria, functioning not only as the central hub of cellular energy metabolism but also as semi-autonomous organelles, orchestrate cellular fate decisions through their endogenous mitochondrial DNA (mtDNA), which encodes core components of the electron transport chain. Emerging research has identified microRNAs localized within mitochondria, termed mitochondria-located microRNAs (mitomiRs). Recent studies have revealed that mitomiRs are transcribed from nuclear DNA (nDNA), processed and matured in the cytoplasm, and subsequently transported into mitochondria. mitomiRs regulate mtDNA through diverse mechanisms, including modulation of mtDNA expression at the translational level and direct binding to mtDNA to influence transcription. Aberrant expression of mitomiRs leads to mitochondrial dysfunction and contributes to the pathogenesis of metabolic diseases. Restoring mitomiR expression to physiological levels using mitomiRs mimics or inhibitors has been shown to improve mitochondrial function and alleviate related diseases. Consequently, the regulatory mechanisms of mitomiRs have become a major focus in mitochondrial research. Given that mitomiRs are located in mitochondria, targeted delivery strategies designed for mtDNA can be adapted for the delivery of mitomiRs mimics or inhibitors. However, numerous intracellular and extracellular barriers remain, highlighting the need for more precise and efficient delivery systems in the future. The regulation of mtDNA expression mediated by mitomiRs not only expands our understanding of miRNA functions in post-transcriptional gene regulation but also provides promising molecular targets for the treatment of mitochondrial-related diseases. This review systematically summarizes recent research progress on mitomiRs in regulating mtDNA expression and discusses the underlying mechanisms of mitomiRs-mtDNA interactions. Additionally, it provides new perspectives on precision therapeutic strategies, with a particular emphasis on mitomiRs-based regulation of mitochondrial function in mitochondrial-related diseases.

Objective: To evaluate the efficacy and safety of plasma exchange (PE) in thymoma-associated myasthenia gravis (MG), thereby to provide theoretical support for its application in the treatment of thymoma-associated MG. Methods: A total of 133 patients with thymoma-associated MG admitted from January 2018 to September 2024 were retrospectively analyzed. Patients were matched using propensity score to reduce selection bias, yielding 22 matched pairs for both PE group (n=22) and non-PE group (n=22). Patient characteristics including gender, age of disease onset, course of disease, history of thymoma resection, clinical absolute scores [clinical absolute scores (CAS) and clinical relative scores (CRS)], and synchronized immunotherapy regimen of the two groups were analyzed. The CAS scores before and after treatment were compared between the two groups, and the CRS was used to assess the treatment efficiency. Safety of the two treatment regimens were also compared. Continuous variables were compared using the t-test or ANOVA, while categorical data were compared by the chi-square test. Results: A total of 133 patients were included and divided into two groups according to whether they underwent plasma exchange treatment: the PE group (n=22) and the non-PE group (n=111). To exclude bias caused by large difference in the number of cases between the two groups, we performed propensity score matching. After matching, the number of cases in both groups was 22. There was no significant difference in baseline clinical characteristics between the two groups (P>0.05), including gender, age of onset, duration of disease course, history of thymectomy and baseline CAS score before treatment. Compared to the non-PE group, patients in the PE group showed more significant improvement in CAS score (5.09±1.95 vs 3.59±1.50, P<0.05) and a higher CRS score (75.00% vs 50.00%, P<0.001). Compared to the non-PE group, PE group had significantly longer ICU stay, longer hospital stay and higher hospitalization cost (P<0.05). There was no statistically significant difference in adverse events between the two groups during treatment (P>0.05). During long-term follow-up, both the PE and non-PE groups showed relatively low 1-, 3-, and 5-year recurrence rate, with no significant difference between the two groups (P>0.05). Conclusion: This study indicates that plasma exchange has clear value in the treatment of patients with thymoma-associated myasthenia gravis. It can not only significantly improve patients' muscle strength to alleviate motor dysfunction and enhance quality of life, but also does not significantly increase the incidence of adverse reactions. Therefore, it can be regarded as one of the preferred treatment options that achieve a "balance between efficacy and safety" for such patients, and provides an important basis for optimizing treatment strategies, improving prognosis, and promoting the application of subsequent treatment regimens.

Aim To evaluate the hypolipidemic effect of the total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) on hyperlipidemic golden hamsters and explore its regulatory effect on intestinal flora. Methods Sixty hamsters were randomly divided into a control group, a model group, a positive drug group, LRTPG-L group, LRTPG-M group, and LRTPG-H group. After the successful induction of the model by high-fat diet, the animals were continuously administered for four weeks, and their blood lipids and liver lipids were detected. The formed feces from the colorectal region of the hamsters in the control group, model group and LRTPG-H group were collected for 16S rDNA sequencing. Results LRTPG reduced serum TG, TC, LDL-C and liver TG, TC concentrations significantly in hyperlipidemic hamsters. The results of the intestinal microbiota sequencing showed that compared to the control group, LRTPG significantly decreased the relative abundance of the phylum Firmicutes and increased the relative abundance of the phylum Bacteroidetes and Verrucomicrobia (P < 0.01) at the phylum level. At the family level, LRTPG significantly increased the relative abundance of Christensenellaceae, Peptococcaceae, and Verrucomicrobiaceae (P < 0.05 or P < 0.01). At the genus level, LRTPG significantly increased the relative abundance of Oscillospira, Oscillibacter, Flavonifractor and Akkermansiaceae (P < 0.05 or P < 0.01). These changes in the flora were beneficial to the hypolipidemic effect of LRTPG. Conclusion LRTPG may exert its hypolipidemic effect by improving the intestinal flora disorder caused by a high-fat diet in golden hamsters.

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09％)were diagnosed with STB,and 54(40.91％)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68％and 66.67％,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95％CI:1.847-9.974,P＜0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56％,higher than 67.42％of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.

Objective:To explore the acupoint selection law of acupuncture and moxibustion in treating diabetic gastroparesis (DGP) using data mining technology.Methods:The clinical literature on acupuncture and moxibustion treatment for DGP was retrieved from CNKI, Wanfang Data, VIP, SinoMed, PubMed, the Cochrane Library from the establishment of the databases to July 31, 2023. The acupoint prescriptions were extracted to Excel 2016 to establish a database, and the statistics of acupoint frequency, meridian, distribution site and specific acupoint use were collected. SPSS Modeler 18.0 was used to analyze the association rules among acupoints, and SPSS Statistics 25.0 was used for clustering analysis and factor analysis to summarize the acupoint selection law for acupuncture treatment of DGP.Results:Totally 153 articles were included, involving 59 acupoints, with a total frequency of 802 times. The 5 most frequently used acupoints were "Zusanli" (ST 36), "Zhongwan" (CV 12), "Neiguan" (PC 6), "Sanyinjiao" (SP 6), "Pishu" (BL 20). The commonly used meridians were stomach meridian, Conception Vessel and bladder meridian. The involved acupoints were mostly located in the chest-abdomen and lower limbs, and most of them were Wushu acupoints, Mu acupoints, and Xiahe acupoints. The core acupoints group was "Zusanli (ST 36)-Zhongwan (CV 12)-Neiguan (PC 6)-Pishu (BL 20)-Weishu (BL 21)-Sanyinjiao (SP 6)-Tianshu (ST 25)", 24 groups of association rules, 5 effective clusters and 6 factors were obtained.Conclusion:Acupuncture and moxibustion treatment of DGP focuses on both spleen and stomach, treating both symptoms and root causes, and uses methods of combining acupoints such as distant and near matching, combining Mu acupoints, and Xiahe acupoints, and combining of Wushu acupoints and Mu acupoints, to achieve the therapeutic effect of nourishing yin and tonifying qi, dispelling upper abdominal fullness and resolving turbidity, and harmonizing stomach and strengthening spleen.

Objective Evaluation of the clinical efficacy of f trochanteric flip osteotomy combined with Kocher-Langen-beck approach for high acetabular posterior wall fracture.Methods Between January 2020 and December 2022,20 patients with high acetabular posterior wall fractures were retrospectively analyzed,including 12 males and 8 females,aged 18 to 75 years old.They were divided into two groups according to the different surgical methods.Ten patients were treated with greater trochanteric osteotomy combined with Kocher-Langenbeck approach as the observation group,including 5 males and 5 fe-males,aged from 18 to 75 years old.Ten patients were treated with Kocher-Langenbeck approach alone as the control group,including 7 males and 3 females,aged from 18 to 71 years old.Matta reduction criteria were used to evaluate the reduction quality of the two groups,and Harris score was used to compare the hip function of the two groups at the latest follow-up.The operation time,blood loss and postoperative complications of the two groups were analyzed.Results All patients were followed up for 10 to 24 months.According to the Matta fracture reduction quality evaluation criteria,the observation group achieved anatomical reduction in 6 cases,satisfactory reduction in 3 cases,and unsatisfactory reduction in 1 case,while the control group only achieved anatomical reduction in 3 cases,satisfactory reduction in 3 cases,and unsatisfactory reduction in 4 cases.At the final follow-up,the Harris hip score ranged from 71.4 to 96.6 in the observation group and 65.3 to 94.5 in the control group.According to the results of Harris score.The hip joint function of the observation group was excellent in 6 cases,good in 3 cases,and fair in 1 case.The hip joint function of the control group was excellent in 2 cases,good in 3 cases,fair in 3 cases,and poor in 2 cases.In the observation group,the intraoperative blood loss ranged from 300 to 700 ml,and the operation dura-tion ranged from 120 to 180 min;in the control group,the intraoperative blood loss ranged from 300 to 650 ml,and the opera-tion duration ranged from 100 to 180 min.Complications in the observation group included 1 case of traumatic arthritis and 1 case of heterotopic ossification,while complications in the control group included 3 cases of traumatic arthritis,3 cases of het-erotopic ossification and 1 case of hip abduction weakness.Conclusions Trochanteric flip osteotomy combined with the Kocher-Langenbeck approach significantly improved anatomical fracture reduction rates,enhanced excellent and good hip joint function outcomes,and reduced surgical complication incidence compared to the Kocher-Langenbeck approach alone.Clinical application of this combined approach is promising,although larger studies are needed for further validation.

Physiologically based pharmacokinetic (PBPK) models have been widely used to predict various stages of drug absorption, distribution, metabolism and excretion. Models based on machine learning (ML) and artificial intelligence (AI) can provide better ideas for the construction of PBPK models, which can accelerate the prediction speed and improve the prediction quality of PBPK. ML and AL can complement the advantages of PBPK model to accelerate the progress of drug research and development. This review introduces the application of machine learning and artificial intelligence in pharmacokinetics, summarizes the research progress of physiological pharmacokinetic models based on machine learning and artificial intelligence, and analyzes the limitations of machine learning and artificial intelligence applications and their application prospects and prospects.

Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.