Journal of Medicine and Life最新文献

Ocular pharmacotherapy is constrained by compartmental anatomy and clearance barriers that limit sustained posterior-segment exposure. Intravitreal bolus dosing, therefore, remains dominant for retinal disease but produces peak-trough profiles and frequent retreatment. Long-acting implants and refillable systems can prolong exposure, yet are finite or maintenance-dependent. Ocular gene therapy introduces a different paradigm in which transduced retinal cells act as localized 'biofactories,' enabling prolonged intraocular production of therapeutic proteins after a single or infrequent administration. This review integrates pharmacokinetic principles with determinants of transgene expression, including vector/capsid design, promoter architecture, route-dependent biodistribution (subretinal, intravitreal, suprachoroidal), and immune modulation, to explain typical kinetics (lag phase, rise to plateau, and potential attenuation). We highlight an infusion-equivalent modeling framework that treats transgene-driven protein output as sustained input balanced by first-order loss, providing parameters for time to plateau, steady-state exposure, and variability. Finally, we discuss translational implications for efficacy and safety, including exposure-response and therapeutic window definition in emerging retinal gene therapy programs (notably anti-VEGF), and future directions such as tunable expression systems and biomarker-linked, model-informed dose optimization.

Gallbladder adenocarcinoma (GBC) is a rare and challenging diagnosis, often associated with chronic gallstones and discovered incidentally during histopathological examination. It may present in early or late stages without overt clinical or radiological signs. Laparoscopic cholecystectomy is commonly performed for gallstones, and in such cases, gallbladder cancer may be detected even in the absence of a visible mass or atypical clinical presentation. A 68-year-old female with no significant medical history presented with a gallstone, confirmed via abdominal ultrasound, showing multiple stones and sludge. The patient underwent an elective laparoscopic cholecystectomy without intraoperative complications, such as bile spillage, significant bleeding, or organ injury. Postoperative recovery was uneventful, with no additional symptoms. Histopathological analysis revealed grade 2 (moderately differentiated) adenocarcinoma extending to the hepatic surface of the gallbladder. Gallbladder adenocarcinoma can present silently in its early stages, underscoring the importance of histopathological examination of all cholecystectomy specimens, especially in older patients with gallstones. Avoidance of bile spillage during surgery is crucial for improving prognosis. Further metastatic evaluation through chest, abdominal, and pelvic CT shows no abnormalities in this case. Regular follow-up with hepatobiliary and oncology teams was recommended.

Achieving effective spasticity management in post-stroke patients remains a significant therapeutic challenge. It requires the anticipation and management of multiple potential complications through a complex, individualized therapeutic approach. The therapeutic goals in stroke-related spasticity vary considerably depending on the intensity and duration of spasticity, as well as the degree of motor control in the affected limb segments. This study presents four clinical case reports involving patients with post-stroke spasticity ranging from grade 1+ to 4 on the Modified Ashworth Scale (MAS), each exhibiting a distinct temporal profile of symptom progression and levels of motor control in affected limbs. All patients received conservative rehabilitation therapy in conjunction with botulinum toxin (BoNT-A) administration. Spasticity assessment is essential for evaluating treatment efficacy and for planning and refining rehabilitation strategies. Employing case-appropriate functional clinical scales facilitates dynamic assessment and quantification of motor deficits, thereby enabling precise definition and ongoing monitoring of therapeutic goals. Given the heterogeneous functional status of patients with post-stroke spasticity, therapeutic objectives and evaluation strategies must be tailored accordingly. BoNT-A therapy necessitates a patient-specific approach concerning dosing and injection intervals. Repeated BoNT-A treatment in cases of severe spasticity produced sustained reductions in limb pain and mitigated periarticular tissue damage. In patients with mild spasticity and preserved motor function, functionality reached substantial recovery, as reflected in outcomes from appropriately selected functional measures, with injections spaced at intervals exceeding three months and employing progressively lower doses.

Restless legs syndrome (RLS) and its association with venous disorders have garnered attention in medical literature. This systematic review aims to consolidate current evidence on the relationship between RLS and various venous pathologies, exploring potential mechanisms, interventions, and clinical implications. A comprehensive search of electronic databases identified relevant studies published up to January 2024. Inclusion criteria comprised studies investigating the association between RLS and venous disorders, encompassing a diverse range of methodologies. Data extraction and quality assessment were performed to ensure the robustness of the included studies. The systematic review included studies that explored associations between RLS and conditions such as superficial venous reflux, varicose veins, and chronic venous insufficiency. Findings from Dezube et al. and Pyne et al. indicated a positive correlation between RLS and superficial venous pathologies, with interventions such as superficial venous ablation and ultrasound-guided foam sclerotherapy showing promising outcomes. Sundaresan et al. extended the exploration to leg vein treatments, reporting improvements in RLS symptoms post-intervention. These results underscore the complexity of the relationship between RLS and venous disorders. The systematic review provides an overview of the current evidence on the association between RLS and various venous pathologies. The positive correlations observed in some studies suggest a potential role for addressing underlying venous pathology in managing RLS symptoms. However, the heterogeneity in study designs and outcomes calls for further research to elucidate the underlying mechanisms and refine targeted interventions.

Antenatal depression is a common complication of pregnancy, with consequences spanning maternal mental health, obstetric outcomes, and early mother-infant adaptation. Effective early identification requires integrating psychological and contextual information alongside validated screening. This study examined whether adult attachment style and the perception of motherhood are associated with antenatal depressive severity in late pregnancy, beyond socio-demographic factors. In a cross-sectional analysis of 140 third-trimester women, adult attachment (Revised Adult Attachment Scale, R-AAS) and depressive symptoms (Edinburgh Postnatal Depression Scale, EPDS) were assessed together with psychosocial indicators (pregnancy planning, partner support, and perception of motherhood). Bivariate associations were tested with χ² (Cramér's V), and multivariable effects with penalized logistic regression for EPDS ≥14, using bootstrap 95% CIs (B = 1000). Secure attachment was associated with minimal risk (0% EPDS ≥14), whereas anxious-ambivalent attachment showed increased vulnerability (49.4% EPDS ≥12). A negative perception of motherhood displayed the most severe profile (60.0% EPDS ≥14 vs 0% in the positive group). In adjusted models, negative perception (aOR = 21.07; 95% CI, 7.92-1317.40) and anxious-ambivalent attachment (aOR = 21.67; 95% CI, 1.00-77.96) retained independent associations, while other covariates were not significant. These findings support a pragmatic psychosocial screening approach for late pregnancy in which a single standardized question on the perception of motherhood and a brief attachment typology add clinically useful information to EPDS. Incorporating these elements into routine antenatal care may enhance early detection and facilitate timely referral to perinatal mental-health services, with multicentre validation needed to support wider implementation.