Objective To explore the factors influencing blood drug concentrations of first-line anti-tuberculosis drugs in fixed-dose combinations by analyzing therapeutic drug monitoring data from tuberculosis patients receiving these regimens.Methods This retrospective study enrolled 224 patients who received treatment at Guangzhou Chest Hospital between January 2020 and December 2024.All participants underwent standardized therapy during the intensive phase,with therapeutic drug monitoring of first-line anti-tuberculosis drugs(ANTDs),including isoniazid(INH)and rifampicin(RFP).Data collection was completed in January 2025,at which time clinical records and measured INH and RFP plasma concentrations were updated.Data analysis was conducted from January to February 2025.Eight baseline variables—gender,age,hypoproteinemia(serum albumin<35 g/L),glomerular filtration rate(GFR),and others—were collected.Univariate chi-square tests and multivariate logistic regression analyses were performed to identify independent risk factors associated with subtherapeutic INH and RFP plasma concentrations.Results Among the study participants,71.43%(160/224)exhibited blood drug concentrations below the reference range for INH,compared to 41.07%(92/224)for RFP.The mean blood concentrations(mg/L,±SD)were 2.532±1.371 for INH and 9.428±4.317 for RFP,respectively.One-way analysis indicated significant associations between male gender,positive etiological test results,and subtherapeutic RFP concentrations(P<0.05),suggesting statistically significant differences.Multivariate regression analysis further revealed that male gender(OR=1.992,95%CI:1.094～3.628)and positive etiological tests(OR=1.929,95%CI:1.058～3.517)were independent risk factors for low RFP levels.Conclusions This study demonstrates that therapeutic drug monitoring(TDM)frequently identifies subtherapeutic RFP concentrations in tuberculosis patients undergoing treatment.Multivariate analysis reveals that male sex and positive pathogen test results are independent risk factors associated with low RFP plasma levels.Consequently,clinicians should exercise heightened vigilance in patients exhibiting these characteristics,promptly implementing TDM to guide individualized dose adjustments.Such an approach is crucial for optimizing treatment efficacy and minimizing the risk of drug resistance development.

Objective To explore the factors influencing blood drug concentrations of first-line anti-tuberculosis drugs in fixed-dose combinations by analyzing therapeutic drug monitoring data from tuberculosis patients receiving these regimens.Methods This retrospective study enrolled 224 patients who received treatment at Guangzhou Chest Hospital between January 2020 and December 2024.All participants underwent standardized therapy during the intensive phase,with therapeutic drug monitoring of first-line anti-tuberculosis drugs(ANTDs),including isoniazid(INH)and rifampicin(RFP).Data collection was completed in January 2025,at which time clinical records and measured INH and RFP plasma concentrations were updated.Data analysis was conducted from January to February 2025.Eight baseline variables—gender,age,hypoproteinemia(serum albumin<35 g/L),glomerular filtration rate(GFR),and others—were collected.Univariate chi-square tests and multivariate logistic regression analyses were performed to identify independent risk factors associated with subtherapeutic INH and RFP plasma concentrations.Results Among the study participants,71.43%(160/224)exhibited blood drug concentrations below the reference range for INH,compared to 41.07%(92/224)for RFP.The mean blood concentrations(mg/L,±SD)were 2.532±1.371 for INH and 9.428±4.317 for RFP,respectively.One-way analysis indicated significant associations between male gender,positive etiological test results,and subtherapeutic RFP concentrations(P<0.05),suggesting statistically significant differences.Multivariate regression analysis further revealed that male gender(OR=1.992,95%CI:1.094～3.628)and positive etiological tests(OR=1.929,95%CI:1.058～3.517)were independent risk factors for low RFP levels.Conclusions This study demonstrates that therapeutic drug monitoring(TDM)frequently identifies subtherapeutic RFP concentrations in tuberculosis patients undergoing treatment.Multivariate analysis reveals that male sex and positive pathogen test results are independent risk factors associated with low RFP plasma levels.Consequently,clinicians should exercise heightened vigilance in patients exhibiting these characteristics,promptly implementing TDM to guide individualized dose adjustments.Such an approach is crucial for optimizing treatment efficacy and minimizing the risk of drug resistance development.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the efficacy and safety of distal transradial access for cerebral angiography and neurointervention.Methods:The literature about distal transradial access for cerebral angiography and neurointervention were searched in PubMed, EMbase, the Cochrane Library, CNKI, WanFang Data, and VIP database from January 2015 to September 2021. Two reviewers independently screened the literature and extracted data according to the inclusion and exclusion criteria, evaluated the literature quality according to the Newcastle-Ottawa scale. The R 4.0.5 software was used for meta-analysis.Results:A total of 12 articles with 987 patients were enrolled. All the studies were retrospective design and did not compare with the results of proximal transradial access and transfemoral access. A meta-analysis of the operation success rate and complication rate using a fixed effect model showed that the operation success rate of distal transradial access was 96% (95% confidence interval 95%-97%), and the incidence of minor complications was 3% (95% confidence interval 2%-4%). One patient had serious complications.Conclusion:The distal transradial access is a safe and effective alternative approach for cerebral angiography and neurointervention.

Objective:To investigate the efficacy and safety of different stents assisted embolization in the treatment of subarachnoid hemorrhage(SAH) caused by V4 dissecting aneurysm of vertebral artery.Methods:The clinical data of 39 patients with spontaneous SAH V4 dissecting aneurysm treated at the Department of Neurosurgery, the Northern Theater General Hospital from January 2016 to June 2019 were analyzed retrospectively.There were 21 males and 18 females, aged (48±17) years(range:35 to 68 years).There were 24 cases of HUNT-HESS grade Ⅰ and 15 cases of grade Ⅱ.Among them, 20 cases were treated with single stent-assisted embolization, 9 cases with multi-stent-assisted embolization, 9 cases with semi-dense mesh-assisted embolization, and 1 case with dense-mesh stent-assisted embolization.The perioperative and postoperative complications, postoperative recurrence were collected.Results:Intraoperative complications included 2 cases of aneurysm rupture and 2 cases of acute thrombosis.All aneurysms were densely packed according to the angiography performed immediately after operation.Postoperative complications included 3 cases of long-term responsible vascular ischemia(modified Rankin score<2). The patients were followed up for 15.1 months(range: 12 to 29 months). At the last follow-up, aneurysms recurrence occured in 10 cases, the recurrence rate was 25.6%(10/39). There were 6 cases of recurrence and 2 cases of complications in 20 cases with single stent-assisted embolization, 3 cases of recurrence and 4 cases of complications in 9 cases with multi-stent-assisted embolization, 1 case of recurrence and 1 case of complications in 9 cases with semi-dense mesh stent.Conclusion:Endovascular treatment is feasible for patients with vertebral artery dissecting aneurysm, and the appropriate surgical method should be selected according to the vascular structure and the location of the aneurysm.

Objective:To investigate the efficacy and safety of different stents assisted embolization in the treatment of subarachnoid hemorrhage(SAH) caused by V4 dissecting aneurysm of vertebral artery.Methods:The clinical data of 39 patients with spontaneous SAH V4 dissecting aneurysm treated at the Department of Neurosurgery, the Northern Theater General Hospital from January 2016 to June 2019 were analyzed retrospectively.There were 21 males and 18 females, aged (48±17) years(range:35 to 68 years).There were 24 cases of HUNT-HESS grade Ⅰ and 15 cases of grade Ⅱ.Among them, 20 cases were treated with single stent-assisted embolization, 9 cases with multi-stent-assisted embolization, 9 cases with semi-dense mesh-assisted embolization, and 1 case with dense-mesh stent-assisted embolization.The perioperative and postoperative complications, postoperative recurrence were collected.Results:Intraoperative complications included 2 cases of aneurysm rupture and 2 cases of acute thrombosis.All aneurysms were densely packed according to the angiography performed immediately after operation.Postoperative complications included 3 cases of long-term responsible vascular ischemia(modified Rankin score<2). The patients were followed up for 15.1 months(range: 12 to 29 months). At the last follow-up, aneurysms recurrence occured in 10 cases, the recurrence rate was 25.6%(10/39). There were 6 cases of recurrence and 2 cases of complications in 20 cases with single stent-assisted embolization, 3 cases of recurrence and 4 cases of complications in 9 cases with multi-stent-assisted embolization, 1 case of recurrence and 1 case of complications in 9 cases with semi-dense mesh stent.Conclusion:Endovascular treatment is feasible for patients with vertebral artery dissecting aneurysm, and the appropriate surgical method should be selected according to the vascular structure and the location of the aneurysm.

Objective To investigate the effect of melatonin on mice with ischemia-reperfusion via a silent information regulator 1 (SIRT1) reducing mitochondrial oxidative stress mechanism. Methods A transient middle cerebral artery occlusion ( MCAO) cerebral ischemia-reperfusion ( IR) model in mice was established by the suture-occluded method. One hundred and ninety mice were injected with melatonin intraperitoneally or the SIRT1 inhibitor (EX527) intracerebroventricularly,30 dead and model failure mice were excluded. They were divided into IR,melatonin,melatonin +EX527,and EX527 groups (n =40 in each group ) according to the random number table. The cerebral infarct volume was detected by the triphenyltetrazolium chloride (TTC) method,the brain edema was measured by the wet and dry weight method and the neurological deficit scores were measured. Western blot was used to detect SIRT1,Ac-P53, acetylated-nuclear factorκB (Ac-NF-κB),BCl2,Bax proteins in the mitochondria and cytoplasm,as well as the cytochrome C protein expression. A single factor analysis of variance was used for comparison among the groups. Results ( 1 ) There were significant differences in cerebral infarction volume, neurological dysfunction scores and cerebral edema among the four groups ( F values,16. 452,23. 622,and 18. 786, respectively (all P<0. 05). There were significant differences in the expression levels of SIRT1,Ac-P53, Ac-NF-κB,BCl2, and Bax among the four groups ( F values, 2348. 158, 1434. 841, 7042. 563, 14627. 128,and 691. 475,respectively,all P<0. 05). There were significant differences in mitochondrial membrane potential,mitochondrial reactive oxygen species,and complex I activity in mice among the four groups (F value,28. 454,33. 728 and 29. 716,respectively,all P <0. 05). (2) Compared with the IR group,the infarct volume was reduced (32 ± 5 mm3 vs. 57 ± 5 mm3,P<0. 05),neurological deficit scores were decreased (2. 4 ± 0. 3 vs. 3. 5 ± 0. 3,P<0. 05);brain edema was reduced (80. 2 ± 0. 9% vs. 83. 9 ± 1. 2%,P<0. 05);the expression levels of SIRT1 and anti-apoptosis protein BCL2 were increased in the melatonin group (P<0. 05);the expression levels of pro-apoptotic protein BAX and Ac-P53,Ac-NF-κB were reduced ( P <0. 05 );the mitochondrial membrane potential, mitochondrial complex I activity and cytochrome C level were increased (P<0. 05);and the cytoplasmic reactive oxygen species and cytochrome C level were decreased (P < 0. 05). (3) Compared with the melatonin group,cerebral infarction volume were increased (42 ± 5 mm3 vs. 32 ± 5 mm3,P < 0. 05);nerve dysfunction scores were increased(3. 2 ± 0. 3 vs. 2. 4 ± 0. 3,P<0. 05);cerebral edema was aggravated (83. 4 ± 0. 8% vs. 80. 2 ± 0. 9%, P < 0. 05 );the expression levels of SIRT1 and anti-apoptotic protein BCL2 were reduced (P <0. 05);the pro-apoptotic protein BAX,Ac-P53,and Ac-NF-κB expression levels were increased (P<0. 05);the mitochondrial membrane potential and mitochondrial complex I activity and cytochrome C level were decreased (P<0. 05);and the cytoplasmic reactive oxygen species and cytoplasmic cytochrome C level were increased in the melatonin+EX527 group (P<0. 05). Conclusion In ischemic stroke model mice, melatonin plays a neuroprotective role by activating the SIRT1 signaling pathway and reducing oxidative stress injury and cell death in mitochondria,thus plays a role in cerebral protection.

Objective To study the level of clinical diagnosis of pulmonary tuberculosis and implementa-tion of tuberculosis prevention and control policy. Methods Frequencies and percentages of pulmonary tuberculosis, other lung diseases and health among 3315 cases with pulmonary tuberculosis suspicious symptoms ,transferred by non-tuberculosis control institutions during 2010-2015,were calculated and analyzed. Results Among the 3315 suspected cases of pulmonary tuberculosis ,cases of pulmonary tuberculosis ,tuberculosis ,other lung diseases and healthy group were 2068,598 and 649 based on final diagnosis and their percentages were 62.38%,18.04% and 19.58% respectively. As to groups of elder than fifteen years ,the proportion of patients with pulmonary tubercu-losis accounts for 72.62%,61.00%and 48.58% of the total of young group(15~44 years old ),middle age group (45 ~ 64 years old)and elderly group(≥ 65 years old )respectively. Conclusions Compared with pulmonary tuberculosis suspicious symptomscases from tuberculosis control institution during the same period ,the proportion of tuberculosis patients from transferred groups is roughly the same.It indicate high levels of tuberculosis diagnosis and implementation to tuberculosis control policy.

Objective Age and sex of the population with suspected pulmonary tuberculosis (PTB) symptoms in Yuexiu District of Guangzhou were analyzed , to find out the prevalence and important risk factors responsible for tuberculosis in this district. Methods New PTB suspects domiciling in Guangzhou Yuexiu District during 2010-2015 were of interests. Data from Guangzhou Tuberculosis Control Project registration book and biobank of Guangzhou Tuberculosis Translational Medicine Center were applied to analyzed the frequency distribution of age and sex of the population. Results 6 154 cases of PTB suspects were included in this study. As to sex,ratio of male to female was 1.70 and there was no obvious fluctuation from 2010 to 2015. Frequency distribution among PTB suspects under 40 had no difference between male and female , but the ratio of male to female was nearly 1.70 for study objects aged above 40.As to age , there was a minor peak in the age group of 25~ while the greater peak was in the age group of 50~ after the age group of 35~. Conclusion In Yuexiu District of Guangzhou ,male were more likely to be the PTB suspects than female , and the peak age of prevalence was between 50 and 60.

Objective To examine the effects of sinomenine (Sin) on inflammatory cell numbers of subarachnoid small perivascular and explore the role of anti-inflammatory of Sin in the treatment of migraine in a rat model of migraine. Methods Healthy wistar rats were randomly divided into 6 groups:normal group, model group and Sin low dose group, Sin middle dose group and Sin high dose group. The rat migraine model was established by subcutaneously administration of nitroglycerin. The brain and mater of rats were decapitated following 4 h of medical intervention. HE staining was used to stain inflammatory cells and inflammatory cells within perivascular spaces were counted under light microscope. Results Compared to normal group, the inflammatory cells (mainly lymphocyte and monocyte) within perivascular spaces were in-creased significantly in model group [(28.10 ± 2.28) vs. (1.60 ± 1.07),P<0.01)];The inflammatory cells in all three Sin groups were significantly reduced compared with model group [Sin high dose group (2.60 ± 1.43)、Sin middle dose group (5.10±1.37)、Sin low dose group (9.10±0.88) vs. (28.10±2.28),P<0.01]. Conclusions Sin can significantly reduce inflam-matory cells within perivascular spaces in the rat model of migraine, suggesting that Sin can effectively treat migraine.