BACKGROUND AND OBJECTIVE

The incidence of ischemic stroke typically increases with age; however, recent studies have shown a concerning trend of stroke cases among adults under the age of 45. This neurologic condition is called “Stroke in the Young” (SITY). SITY poses public health concerns due to its long-term consequences on individuals and their families. Despite significant impact, published literature on SITY among Filipinos is scarce. Given the potential differences in genetic background and lifestyle, the clinical characteristics and outcomes of SITY Filipinos may vary considerably from other populations. Therefore, the aim of this study is to describe the clinical features and outcomes of ischemic SITY Filipinos.

The study was a two-center, five-year retro- spective cohort design involving 19- to 45-year-old  patients admitted between January 1, 2017, and December 31, 2022, diagnosed clinically and radiologically with ischemic stroke for the first time. Medical records were reviewed, including demographic data, stroke symptoms, cardiovascular or non-cardiovascular risk factors, and laboratory results. Ischemic stroke subtypes were categorized into cardioembolic, small artery occlusion, stroke of other determined causes, and stroke of undetermined cause through the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. Functional outcomes on hospital discharge were assessed by the Modified Rankin Scale (mRS). All data were analyzed using descriptive statistics in the Statistical Package for the Social Sciences (SPSS software, version 29).

A total of 205 cases of ischemic SITY were chart reviewed. The mean age was 37.30, with a female predominance of 68.3%. The most reported cardiovascular risk factors were obesity (56.6%), hypertension (51.2%), heavy alcohol consumption (36.5%), and diabetes mellitus type 2 (19.5%). Concurrently, the non-cardiovascular risk factors identified were pregnancy, particularly in the postpartum period (4.8%), use of estrogen-containing pills (4.8%), and migraine without aura (4.4%). Based on TOAST classification, small vessel occlusion (42.1%) and large artery atherosclerosis (30.2%) were the most frequent ischemic stroke subtypes of SITY Filipino females. Mostly showed no symptoms of disability (35.1%) on hospital discharge.

This study highlights the difference in the clinical profile of young Filipino adults with ischemic stroke. Contrary to previous studies, ischemic stroke was more predominant among young females. Aside from hypertension, obesity has emerged as the leading cardio- vascular risk factor for ischemic SITY. Moreover, noncardiovascular risk factors, specific to females (pregnancy, use of estrogen-containing pills, and migraine), were also identified in the study. With regards to stroke subtypes, small vessel occlusion and large artery atherosclerosis were frequently seen in young female patients. These f indings suggest a need for gender-specific approaches in the evaluation, management, and prevention of ischemic SITY.

OBJECTIVES

This study aimed at determining the association of the clinical profile of patients with GDM to maternal and neonatal outcomes

This single-center, retrospective, descriptive, cross-sectional chart review was conducted in a tertiary hospital in Cebu City to 229 patients with GDM admitted from January 2021 to December 2022.

The study revealed several significant associations. Hypertension was strongly linked with primary cesarean section (OR: 4.32, P-value 0.004); and severe pre-eclampsia (OR: 16.97, P-value: 0.000). Gravidity showed significant correlations with Ballard’s score (P-value: 0.013), birthweight (P-value: 0.045) and 5-minute APGAR score (P-value: 0.001). Parity was associated with birthweight (P-value: 0.011) and 5-minute APGAR score (P-value: 0.001). Weight gain during pregnancy was linked to birthweight (P-value: 0.004) and occurrence of congenital anomalies (OR: 1.26, P-Value: 0.032). Additionally, prenatal smoking was associated with 5-minute APGAR score (P-value: 0.006). Moreover, having a Small for Gestational Age (SGA) fetal growth status is associated with insulin-requiring mothers, (OR: 4.79, P-Value: 0.049); and a family history of diabetes was significantly associated with insulin therapy (OR: 5.38, P-value: 0.021).

Patients' clinical profile affect maternal and neonatal outcomes among patients with GDM. Careful consideration of these factors during the perinatal period may help reduce maternal and fetal risks

Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

AIM To investigate the protective effects of verbascoside on D-galactose-induced liver injury in mice and its underlying mechanisms.METHODS C57BL/6J mice were randomly assigned to the normal group,the model group,the vitamin E group(100 mg/kg),and the low-dose and high-dose verbascoside groups(40,80 mg/kg),with 10 mice in each group.Simultaneous administration of medicine and subcutaneous injection of D-galactose(600 mg/kg)went on among the groups except the normal group for 8 weeks.Serum ALT,AST,ALP activities,along with TBil levels were measured using biochemical kits.Hepatic GSH,MDA concentrations,as well as SOD and GSH-Px activities were quantified.Liver pathological morphology was evaluated by HE staining,while hepatic fibrosis area was assessed using Sirius red staining.Western blot analysis determined hepatic expression of IL-6,IL-1β,TNF-ɑ,TLR4,NF-κB p65,IκBɑ and p-IKBɑ proteins.RESULTS Compared to the model group,the groups treated with vitamin E or verbascoside demonstrated significantly reduced body weight(P＜0.05,P＜0.01);increased hepatic index(P＜0.05,P＜0.01);decreased serum activities of ALT,AST and ALP alongsided reduced TBil levels(P＜0.05,P＜0.01);attenuated pathological damage of liver tissue and fibrosis severity;reduced hepatic MDA level(P＜0.05,P＜0.01);and elevated GSH level with enhanced SOD and GSH-Px activities(P＜0.05,P＜0.01).Furthermore,the high-dose verbascoside group showed significantly decreased hepatic expressions of IL-6,IL-1 β,TNF-ɑ,TLR4,NF-κB p65,and p-IKBɑ/IKBɑ proteins(P＜0.05,P＜0.01).CONCLUSION Verbascoside improves D-galactose-induced liver injury through its antioxidant activity,anti-inflammatory effects,and suppression of the TLR4/NF-κB signaling pathway.

Objective:To investigate the role and molecular mechanisms of transcription factor EB (TFEB) and its target genes in the treatment of multiple myeloma (MM) with bortezomib.Methods:TFEB target genes were predicted using the GTRD database (http://gtrd.biouml.org/), identifying Ptch1 gene for further study. Expression changes of Ptch1 in RPMI8226 and U266 MM cell lines after bortezomib treatment were assessed by real time fluorogenic quantitative PCR (RT-qPCR) and Western blot. RPMI8226 and U266 cell lines were transfected with siRNA-TFEB, and mRNA and protein levels of key factors (Ptch1, Gli1) in the Ptch1/Hedgehog signaling pathway were measured by RT-qPCR and Western blot. Furthermore, Ptch1 was overexpressed in MM cell lines via lentiviral transduction. Autophagy was evaluated by acridine orange staining, and protein levels of LC3B, Beclin-1, and Lamp-1 were measured by Western blot. Lysosomal quantity changes were assessed by lysosomal fluorescent probes.Results:Bortezomib (6.0×10 -6 mmol/L, 24 h) significantly reduced Ptch1 mRNA and protein levels in both cell lines compared with blank control group (all P<0.05). siRNA-TFEB transfection reversed bortezomib’s inhibition of Hedgehog pathway key factors Ptch1 and Gli. Ptch1 overexpression in bortezomib-treated RPMI8226 and U266 cells significantly reduced the relative expression of autophagy-related proteins LC3B, Beclin-1, and Lamp-1 (all P=0.001). Acridine orange staining showed fewer acidic vesicular organelles within two cell lines (all P=0.001). The relative fluorescence expressions of lysosomal probes reflecting the number of lysosomes were also decreased ( P values of RPMI8226 and U266 cell lines were 0.001 and 0.007, respectively) . Conclusion:The knockdown of TFEB can specifically promote the expression of the Ptch1/Hedgehog signaling pathway, thereby reducing bortezomib-induced autophagy in MM cells and reversing the inhibitory effect of bortezomib on the proliferation of MM cell lines.

Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular condition where the superior mesenteric artery is affected by dissection without involving other arteries. Its incidence is estimated at 0.06% to 0.08% globally. Possible causes include trauma, congenital connective tissue disorders, arteriosclerosis, and vasculitis such as polyarteritis nodosa (PAN). SISMAD can manifest with various clinical presentations, from asymptomatic to acute bowel ischemia, warranting consideration when common causes of acute abdomen are ruled out.

This is a case of a 44-year-old female Filipino, who complained of abdominal pain, initially managed as intestinal amoebiasis. Abdominal examination showed a soft, non-tender abdomen with no guarding, making the symptoms disproportionate to physical examination. Due to persistence of symptoms despite full antibiotic course, further work up was done. Computed tomography (CT) scan of the whole abdomen with contrast revealed an isolated dissection of the proximal superior mesenteric artery (SMA) with thrombosis which was confirmed on CT angiography. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), cytoplasmic antineutrophilic cytoplasmic antibodies (ANCA) and perinuclear ANCA were both negative; antinuclear antibody (ANA), C3 and C4 levels were also unremarkable. The diagnosis of PAN was established based on the correlation of clinical presentation, laboratory findings, and imaging results. She was given methylprednisolone pulse therapy and cyclophosphamide with good response. Anticoagulation with heparin was initiated to address the thrombosis. The patient had complete bowel rest, pain management, intravenous hydration, and parenteral nutrition. Resolution of symptoms noted and was eventually discharged improved.

SISMAD and PAN are independently rare conditions. This unique case involved both diseases in a 44-year-old Filipino female. Early diagnosis of the disease requires a high degree of suspicion and pattern recognition. This is crucial for timely treatment and improved prognosis. Furthermore, close surveillance is important to identify potential relapses even after symptom resolution.

BACKGROUND

Intraoperative transfusion for gynecologic surgery, when appropriately used, can improve patient outcomes. However, when utilized incorrectly, blood transfusion can worsen patient outcomes and increase patient cost. This study aimed to evaluate the blood transfusion practices of tertiary hospitals in the Philippines.

The study utilized a cross-sectional design wherein prospective data were gathered through multiple sources across seven tertiary-level hospitals. Women admitted to undergo gynecologic surgery were recruited based on a set of criteria. A chart review was conducted, and blood utilization indices were calculated. Outcomes were compared between public versus private facilities and transfused versus nontransfused patients.

Among 514 patients, 79.7% underwent cross-matching and 75.1% received transfusions. Adverse events were rare, with no transfusion-related deaths. The overall crossmatch-to-transfusion ratio (C/T ratio) was 2.8, exceeding the 2.5 optimal benchmark; all public hospitals recorded a C/T ratio >2.5, whereas private centers had more efficient usage. Six hospitals met acceptable benchmarks for transfusion probability and transfusion index. Open abdominal procedures, particularly hysterectomy, accounted for the most blood used. Transfused patients had longer operative times, greater blood loss, lower preoperative hemoglobin, and more frequently involved resident physicians in training. Public hospitals recorded higher cross-match and transfusion rates, greater resident physician participation, and broader use of general anesthesia.

Results of the study highlight the importance of monitoring blood transfusion parameters to optimize blood utilization. The observed differences between public and private institutions in the country highlight the urgent need for standardized and evidence-based practice to ensure efficient transfusion protocols nationwide.

Objective To investigate the mechanisms by which astaxanthin(AST)alleviates oxaliplatin(OXA)-induced neuropathic pain through antioxidant pathways so as to provide theoretical basis for clinical intervention.Methods Animal experiments:SD rats were divided into five groups(n=6):control group,OXA(4 mg/kg)group,OXA+Oil group,OXA+AST(5 mg/kg)group,and OXA+AST(10 mg/kg)group.Mechanical and cold pain thresholds were measured at day 0,7,14,and 21.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity in the dorsal root ganglia(DRG)were detected using the thiobarbituric acid(TBA)method and WST-1 assay,respectively.Western blotting was performed to analyze the expressions of Nrf2 and HO-1.Cell experiments:neuro-2a cells were divided into control group,OXA(50 μmol/L)group,AST(10 μmol/L)group,and OXA(50 μmol/L)+AST(10 μmol/L)group.Cells were treated with nerve growth factor(NGF,50 ng/mL)to induce growth,and morphological changes were observed under an inverted microscope.Intracellular reactive oxygen species(ROS)level and mitochondrial superoxide were measured using DCFH-DA fluorescent probe and MitoSOXTM red,respectively.Mitochondrial function was assessed by JC-1 assay.Western blotting was used to detect Nrf2 and HO-1 expressions.Results Animal experiments:① Mechanical and cold pain thresholds were reduced in OXA and OXA+Oil groups(P＜0.05),while AST significantly increased these thresholds in OXA-treated rats(P＜0.05).② SOD activity decreased while MDA content increased in the DRG of OXA-treated rats(P＜0.05).AST restored SOD activity and reduced MDA level(P＜0.05,P＜0.01).③ Western blotting showed elevated Nrf2 and HO-1 expressions in OXA group(P＞0.05),which were further upregulated by AST(P＜0.05,P＜0.01).Cell experiments:① OXA reduced the number of neurite-bearing cells and shortened the average neurite length(P＜0.05).Inverted microscopic observation revealed that AST intervention increased both parameters(P＜0.01,P＜0.001).② OXA increased intracellular and mitochondrial ROS fluorescence intensity(P＜0.05),which was attenuated by AST(P＜0.01).③ JC-1 assay revealed decreased mitochondrial membrane potential in OXA group(P＜0.01),which was partially reversed by AST(P＜0.05).④ Western blotting results showed that OXA upregulated Nrf2 and HO-1 expressions(P＜0.05,P＜0.01),and AST further enhanced their levels(P＜0.01).Conclusion AST alleviates OXA-induced neuropathic pain by promoting Nrf2/HO-1 expression,enhancing SOD activity,reducing lipid peroxidation and ROS production,and improving mitochondrial function.

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men, the incidence of which gradually increases with age and leads to lower urinary tract symptoms (LUTS), which seriously affects the quality of life of patients. Chinese herbal medicines (CHMs) are widely used for the treatment of BPH in China and some other countries. To explore the molecular mechanisms of CHMs for BPH, we conducted a review based on peer-reviewed English-language publications in PubMed and Web of Science databases from inception to December 31, 2023. This article primarily reviewed 32 papers on the use of CHMs and its active compounds in the treatment of BPH, covering animal and cell experiments, and identified relevant mechanisms of action. The results suggest that the mechanisms of action of CHMs in treating BPH may involve the regulation of sex hormones, downregulation of cell growth factors, anti-inflammatory and antioxidative effects, inhibition of cell proliferation, and promotion of apoptosis. CHMs also exhibit α-blocker-like effects, with the potential to relax urethral smooth muscle and alleviate LUTS. Additionally, we also reviewed 4 clinical trials and meta-analyses of CHMs for the treatment of BPH patients, which provided initial evidence of the safety and effectiveness of CHMs treatment. CHMs treatment for BPH shows advantages as a multi-component, multi-target, and multi-pathway therapy, which can mitigate the severity of the disease, improve LUTS, and may become a reliable treatment option in the future.
Prostatic Hyperplasia/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Male ; Animals