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.

Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a rare congenital disorder characterized by the absence or underdevelopment of the uterus and upper part of the vagina in females with a normal 46, XX karyotype. It affects approximately 1 in 4500–5000 female live births and ranks as the second-most common cause of primary amenorrhea. This case report describes a 28-year-old nulligravid woman who presented with primary amenorrhea, difficulties during sexual intercourse manifesting as pain and resistance, and an incidental finding of a right ovarian new growth. Physical examination revealed normal secondary sexual characteristics and a blind-ending vagina measuring 5 cm in depth. Transvaginal ultrasound confirmed the presence of a transverse vaginal septum with hematocolpos, an infantile uterus with endometrium and cervix, a right ovarian new growth, and a normal left ovary. Both kidneys appeared normal, and hormonal assays were within normal limits. Karyotype analysis confirmed a genotype of 46, XX, indicating a normal chromosomal complement for a female without any detectable structural or numerical chromosomal abnormalities, consistent with typical female development. She subsequently underwent ultrasound-guided excision of the transverse vaginal septum combined with laparoscopic oophorocystectomy. Intraoperatively, findings included a normal left ovary, a right ovarian new growth, absence of fallopian tubes, and an infantile uterus. Histological analysis confirmed a serous cystadenoma in the right ovary. Karyotype analysis confirmed a genotype of 46, XX. The index case was diagnosed with MRKH type II (atypical), characterized by the absence of fallopian tubes and a right ovarian new growth without associated renal, skeletal, or cardiac anomalies.

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.

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

Objective To investigate the efficacy of Fumai Zhuyu Decoction combined with radial shock wave therapy(RSWT)in treating convalescent stroke patients with lower limb spasm,and to observe its effect on serum neuron-specific enolase(NSE)and transforming growth factor-β1(TGF-β1).Methods From January 2022 to January 2024,a total of 111 convalescent stroke patients with lower limb spasm of qi deficiency and blood stasis syndrome were selected from the First Affiliated Hospital of Hebei North University.According to the treatment method,the patients were divided into two groups.The 55 patients in the western medicine(WM)group were treated with RSWT,and 56 patients in the traditional Chinese medicine(TCM)group were treated with Fumai Zhuyu Decoction orally and RSWT.The course of treatment for the two groups covered 6 months.Before and after treatment,the two groups were observed in the changes of modified Ashworth Scale(MAS)score for the evaluation of muscle tone of hemiplegic limbs,Clinical Spasticity Index(CSI)score,Barthel Index(BI)score for the evaluation of activities of daily living,three-dimensional gait parameters(velocity,cadence,step length),serum levels of NSE and TGF-β1,and hemorheological indicators of plasma viscosity(PV),low-shear blood viscosity(LBV),high-shear blood viscosity(HBV)and platelet aggregation rate(PAR).After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate of the TCM group was 94.64%(53/56),and that of the WM group was 76.36%(42/55).The intergroup comparison(tested by chi-square test)showed that the efficacy of the TCM group was significantly superior to that of the WM group(P＜0.01).(2)After treatment,the MAS and CSI scores of the two groups were lowered(P＜0.05)and the BI scores were increased compared with those before treatment(P＜0.05).The decrease of MAS and CSI scores and the increase of BI scores in the TCM group were significantly superior to those in the WM group(P＜0.01).(3)After treatment,the three-dimensional gait parameters of velocity,cadence,and step length in the two groups were increased compared with those before treatment(P＜0.05),and the increase of gait parameters in the TCM group was significantly superior to that in the WM group(P＜0.01).(4)After treatment,the serum NSE level of the two groups was significantly decreased that before treatment(P＜0.05),and the serum TGF-β1 level was significantly increased compared with that before treatment(P＜0.05).The decrease of serum NSE level and the increase of serum TGF-β1 level in the TCM group were significantly superior to those in the WM group(P＜0.01).(5)After treatment,the hemorheological indexes such as PV,LBV,HBV and PAR in the two groups were significantly lowered compared with those before treatment(P＜0.05),and the decrease in the TCM group was significantly superior to that in the WM group(P＜0.01).Conclusion Fumai Zhuyu Decoction combined with RSWT can effectively improve the limb spasm degree and walking function,reduce serum NSE level,increase serum TGF-β1 level,and correct the abnormal blood hemorheology in convalescent stroke patients with lower limb spasm of qi deficiency and blood stasis syndrome.The curative effect of the combined treatment is significantly superior to that of RSWT alone.

Objective To evaluate the effects of Qitan Decoction(QTD)combined with radial shockwave therapy(RSWT)on walking ability,balance function,and neural injury markers in stroke patients with lower limb spasticity during convalescence.Methods A retrospective study was conducted on 100 stroke patients with lower limb spasticity of qi deficiency and blood stasis type treated at the First Affiliated Hospital of Hebei North University from December 2021 to December 2023.Patients were divided into a conventional group(n=49,receiving RSWT alone)and an trial group(n=51,receiving RSWT plus QTD)based on treatment protocols.Both groups received standard stroke care(including cerebral metabolism improvement,neurotrophic support,and antiplatelet therapy).The intervention lasted 6 months.The changes in Modified Ashworth Scale(MAS)scores,Functional Gait Assessment(FGA)scores,Berg Balance Scale(BBS)scores,Stroke-Specific Quality of Life(SS-QOL)scores,serum neural injury markers[gama-aminobutyric acid(GABA),brain-derived neurotrophic factor(BDNF)],and kinematic parameters(peak knee flexion,peak hip flexion)were observed,and the clinical efficacy was compared between groups.Results(1)After 6 months of treatment,the total effective rate of the trial group was 94.12％(48/51),and that of the conventional group was 75.51％(37/49),and the intergroup(by chi-square test)comparison showed that the efficacy of the trial group was significantly superior to that of the conventional group(P＜0.01).(2)After treatment,the MAS scores of patients in the two groups were lower than before treatment(P＜0.05),and the FGA,BBS,and SS-QOL scores were higher than before treatment(P＜0.05),and the reduction of the MAS scores and the increase of the FGA,BBS,and SS-QOL scores of the trial group were significantly superior to those of the conventional group(P＜0.01).(3)After treatment,the serum GABA and BDNF levels of patients in the two groups were higher than those before treatment(P＜0.05),and the increase in serum GABA and BDNF levels in the trial group was significantly superior to that in the conventional group(P＜0.01).(4)After treatment,the peak knee flexion and peak hip flexion of patients in the two groups were elevated compared with those before treatment(P＜0.05),and the trial group's elevation of peak knee flexion and peak hip flexion was significantly superior to that of the conventional group(P＜0.01).Conclusion QTD combined with RSWT effectively alleviates spasticity,enhances walking/balance function,mitigates neural injury,and improves quality of life in stroke patients with lower limb spasticity of qi deficiency and blood stasis syndrome during convalescence.