Treatment Strategies Research Articles

Functional Outcome Prediction of Acute Ischemic Stroke Based on the Oral and Gut Microbiota.

Although several studies have identified a distinct gut microbiota in individuals with acute ischemic stroke (AIS), there is a limited amount of research that has simultaneously investigated alterations in the oral and intestinal microbiota in AIS patients and their correlation with clinical prognosis. This was a prospective and observational single-center cohort study in which we included 160 AIS patients who were admitted within 24h after a stroke event. We collected oral and rectal swab samples for analysis using 16S rRNA high-throughput sequencing. Our study revealed that patients with unfavorable outcomes after AIS showed early disruptions in their oral and intestinal microbiota. Rectal swabs showed increased levels of facultatively anaerobic bacteria in patients with a poor prognosis, while the oral cavity exhibited higher levels of anaerobic and opportunistic pathogenic bacteria. By employing machine learning analysis, we found that the microbiota composition at both rectal and oral sites could predict early and long-term outcomes. Moreover, patients with a poor prognosis displayed increased oral bacterial colonization in the rectal microbiota and altered interactions between the oral and gut microbiota. This study reveals distinct rectal and oral bacteria that could predict unfavorable outcomes for AIS patients. Monitoring the microbiota of various body sites during the early stages after admission may hold prognostic value and inform personalized treatment strategies. The presence of oral bacteria colonizing the intestines during the acute phase of stroke could serve as an early indication of poor outcomes for AIS patients.

Subtyping colorectal cancer based on septic shock-associated genes: prognosis and immune characteristics

BackgroundSepsis and colorectal cancer (CRC) are leading causes of death. Given their mutual dependence for susceptibility, we used bioinformatics to explore potential connections between septic shock (SS) and CRC.MethodsWe identified 452 co-expressed genes between SS-related differential expression genes (SS-DEGs) and CRC patient-expressed genes (TCGA-CRC genes). CRC samples were categorized into two cluster subgroups through hierarchical clustering. We then compared the prognosis and immune landscapes of the two cluster subgroups through survival analysis, immune microenvironment analysis, and immune therapy response evaluation.ResultsClustering analysis of the 452 CRC patient-expressed SS-DEGs identified two subtypes: SS-like CRC (SL-CRC) and non-SS-like CRC (NSL-CRC). There were no significant differences in overall survival between the CRC subtypes. However, the subtypes displayed significant differences in immune score, stromal score, and ESTIMATE score. Based on immune therapy databases, there were also significant differences in responses to anti-CTLA-4 and anti-PD-1 immune checkpoint inhibitors between the subtypes.ConclusionOur study reveals significant differences in the immune microenvironment and immune therapy responses between SL-CRC and NSL-CRC subtypes. These findings provide a foundation for identifying new therapeutic targets and developing personalized treatment strategies for specific CRC subtypes.

Gut Microbiota’s role in lipoma development: evidence from mendelian randomization

BackgroundLipoma, a benign tumor derived from mesenchymal tissue, significantly affects patients’ physical and psychological wellbeing. Increasing evidence points to a strong link between the gut microbiome (GM) and lipoma incidence. This study utilizes Mendelian Randomization (MR) to assess the potential causal relationships between the GM and lipoma development.MethodsWe conducted a two-sample MR analysis using genome-wide association study (GWAS) data from MiBioGen and FinnGen to explore the causal relationship between GM and lipoma. The GM dataset included 18,340 participants with 14,587 single nucleotide polymorphisms (SNPs), while the lipoma dataset comprised 412,181 participants with 21,306,349 SNPs. We employed 5 MR methods: Inverse Variance Weighted (IVW), Weighted Median, Simple Mode, MR-Egger, and Weighted Mode. Additional assessments included Cochran’s Q test for result heterogeneity, PRESSO analysis for horizontal pleiotropy, and sensitivity analyses through scatter plots, leave-one-out analyses, funnel plots, and forest plots.ResultsThe IVW method identified 18 gene predictors trans-genus associated with lipoma risk. Protective effects against benign lipoma (BL) were observed in the Eubacterium rectale group, Desulfovibrio, Ruminococcus1, Clostridium sensu stricto1, and Lachnospiraceae UCG001; conversely, Lachnospiraceae UCG008 was linked to increased BL risk. Desulfovibrio provided protection against TS-BL; however, the Family XIII AD3011 group, Eubacterium coprostanoligenes group, Lachnospiraceae NK4A136 group, and Parasutterella were associated with an increased TS-BL risk. The Clostridium innocuum group, Eubacterium rectale group, Anaerotruncus, Ruminiclostridium6, and Lachnospiraceae UCG001 offered protection against LS-BL, while Lachnospiraceae UCG008 was linked to an increased LS-BL risk. The Eubacterium brachy group, Odoribacter, Butyricimonas, Subdoligranulum, and Clostridium sensu stricto1 were protective against HFNS-BL; Ruminococcaceae UCG005 was associated with an increased HFNS-BL risk.ConclusionCompared to malignant tumors, research on lipomas has been relatively limited. This study, through MR analysis, provided new evidence of a causal relationship between specific GM and the development of lipomas. Certain gut bacterial species may act as protective or harmful factors in lipoma formation, offering new avenues for future treatment strategies. However, additional research is required to unravel the complexity of how GM influences the pathogenesis of lipomas.

Clinically Significant Prostate Cancer Prediction Using Multimodal Deep Learning with Prostate-Specific Antigen Restriction

Prostate cancer (PCa) is a clinically heterogeneous disease. Predicting clinically significant PCa with low–intermediate prostate-specific antigen (PSA), which often includes aggressive cancers, is imperative. This study evaluated the predictive accuracy of deep learning analysis using multimodal medical data focused on clinically significant PCa in patients with PSA ≤ 20 ng/mL. Our cohort study included 178 consecutive patients who underwent ultrasound-guided prostate biopsy. Deep learning analyses were applied to predict clinically significant PCa. We generated receiver operating characteristic curves and calculated the corresponding area under the curve (AUC) to assess the prediction. The AUC of the integrated medical data using our multimodal deep learning approach was 0.878 (95% confidence interval [CI]: 0.772–0.984) in all patients without PSA restriction. Despite the reduced predictive ability of PSA when restricted to PSA ≤ 20 ng/mL (n = 122), the AUC was 0.862 (95% CI: 0.723–1.000), complemented by imaging data. In addition, we assessed clinical presentations and images belonging to representative false-negative and false-positive cases. Our multimodal deep learning approach assists physicians in determining treatment strategies by predicting clinically significant PCa in patients with PSA ≤ 20 ng/mL before biopsy, contributing to personalized medical workflows for PCa management.

A low-fat amino acid diet reverses intestinal failure and shows good growth trends in five infants with diacylglycerol transferase 1 (DGAT1) deficiency: a prospective cohort study.

Congenital diarrheas and enteropathies (CODEs) caused by diacylglycerol transferase 1 (DGAT1) mutations often cause disease within 2 weeks after birth. If not treated properly, the disease can be life-threatening; therefore, early diagnosis and rational treatment strategies are essential. This study was conducted to improve the understanding of congenital diarrhea caused by DGAT1 deficiency. Clinical data from five congenital diarrhea infant cases caused by DGAT1 deficiency were analyzed. Infants were prospectively provided with a nutritional intervention with a low-fat amino acid formula for special medical purposes (FSMP). Their gastrointestinal symptoms and nutritional complications before and after interventions were compared. Due to poor weight gain and gastrointestinal symptoms after birth, infants were treated by our clinical nutritionist. Genetic testing confirmed a compound heterozygous mutation in DGAT1. Neither hydrolyzed nor high-medium chain triglyceride (MCT) formula significantly alleviated diarrheal symptoms; however, a low-fat amino acid diet rapidly relieved symptoms and significantly improved nutritional status, with infants showing better tolerance to dietary fat content with age. Infants with DGAT1 deficiency can be diagnosed by genetic testing. A low-fat amino acid FSMP formula and diet can quickly relieve diarrhea, vomiting, and other symptoms, and also improve infant growth and development. Ethical approval was obtained from the Medical Ethics Committee of the Children's Hospital of Fudan University (reference code: No.(2022)405).

Excitatory amino acids as therapeutic agents: Reversing neurodegenerative trajectory by tackling excitotoxicity.

Neurodegenerative diseases pose significant challenges to healthcare systems globally due to their complex etiology and relentless progression, often rendering conventional treatments ineffective. Recent advances have spotlighted excitatory amino acids, particularly D-amino acids, once considered as products of metabolism of the microbiota or deriving from food intake. This review explores the role of D-amino acids in mitigating excitotoxicity-a process characterized by excessive calcium influx through aberrant N-methyl-D-aspartate receptor (NMDAR) activation, which is implicated in the pathogenesis of diseases like Alzheimer's disease. By providing alternative pathways for neuronal signaling and protecting against excitotoxic damage, D-amino acids offer a novel approach to reversing neurodegenerative trajectories. Future research should focus on elucidating the detailed mechanisms of action of these compounds, evaluating their therapeutic potential through rigorous preclinical and clinical trials, and developing effective delivery systems to optimize their neuroprotective effects. This emerging field holds promise for developing innovative treatment strategies that could significantly improve outcomes for patients with neurodegenerative disorders.

Progress and perspectives on BMP9-ID1 activation of HIF-1α and VEGFA to promote angiogenesis in hepatic alveolar echinococcosis

Hepatic alveolar echinococcosis is a zoonotic disease with a high incidence in western China, particularly affecting plateau areas such as Qinghai, Tibet, and Xinjiang. Research has indicated the presence of neovascularization in the peripheral infiltration area of hepatic alveolar echinococcosis, with a strong correlation between angiogenesis and vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1-alpha (HIF-1α) overexpression. Given the similarities between hepatic alveolar echinococcosis and liver cancer, current research is focused on treating the disease by targeting related signaling pathways using molecular drugs used for liver cancer. This article aims to summarize the biological regulation of HIF-1α and VEGFA overexpression in angiogenesis related to hepatic alveolar echinococcosis, as well as the impact of the BMP9-ID1 signaling pathway on the expression levels of HIF-1α and VEGFA, providing new insights for potential treatment strategies.

Dengue Cardiomyopathy Treatment Strategy Optimisation by Integrating Point-of-Care Ultrasound with VExUS

Dengue fever is an arthropod-borne viral disease that is widespread throughout the world. Herein, we report a case of dengue cardiomyopathy that was detected and treated to best effect using point-of-care ultrasound (POCUS) and the VExUS score. A 75-year-old lady with no known comorbidities presented with a 10-day history of fever, vomiting, loose stool, and poor appetite. Upon arrival, she was febrile and hypotensive. Bedside POCUS showed poor left ventricular systolic function, inferior vena cava measuring 2.27cm and VExUS grading of 2 to 3. Dengue serology IgM and IgG were positive and NT-proBNP raised at 12500pg/ml. Instead of fluid resuscitation, diuretic and inotropes were initiated along the line of cardiogenic shock secondary to dengue cardiomyopathy. Serial normal cardiac enzymes and electrocardiogram excluded acute coronary syndrome. She was discharged well, and repeated echocardiography one-month post discharge showed normal left ventricular systolic function with no clinical signs or symptoms of heart failure.

Whole-exome sequencing reveals novel genomic signatures and potential therapeutic targets during the progression of rectal neuroendocrine neoplasm.

Rectal neuroendocrine neoplasms (rNENs) are among the most frequent gastrointestinal neuroendocrine neoplasms and pose a serious challenge for clinical management. The size of the primary neoplasm is considered to be the most important predictor of disease progression, but the genetic alterations that occur during the progression of rNENs remain unknown. Here, we performed a comprehensive whole-exome sequencing study on 54 tumor-normal paired, formalin-fixed paraffin-embedded specimens from patients locally diagnosed with rNENs. Of these, 81.5% (n = 44) were classified as small-sized (≤2 cm) rNENs, while the remainder (18.5%, n = 10) were classified as large-sized (>2 cm) rNEN samples. Comparative analysis revealed marked disparities in the mutational landscape between small- and large-sized rNEN samples, and between large-sized rNEN samples with or without lymph node metastases. The high-confidence driver genes RHPN2, MUC16, and MUC4 were significantly mutated in both small- and large-sized rNEN specimens, whereas mutations in MAN2A1, and BAG2 were only identified in large-sized specimens diagnosed with lymph node metastases. Correspondingly, we observed that the mTOR and MAPK pathways were preferentially enriched in the large-sized rNEN specimens. Signature-based analysis revealed that mutational processes associated with defective DNA base excision repair (SBS30) significantly accumulated in large-sized rNEN samples with lymph node metastases, highlighting the important role of this mutagenic process in promoting rNEN progression. We further found that most rNEN subjects, regardless of tumor size, harbored at least one alteration with targeted therapeutic implications. Taken together, these results elucidate the genetic features associated with tumor size and lymphatic metastasis in rNEN patients, which will deepen our understanding of the genetic changes during rNEN progression and potentially directing improvements in rNEN treatment strategies.

Paradigms in periorbital scar management

Periocular scarring following surgery or trauma is of great aesthetic and functional concern and is difficult to predict. In today’s era, with increasing scientific knowledge and technological advances, both physicians and their patients are highly concerned with minimizing scar appearance as a rising number of patients feel disappointed with their scars and are frequently seeking help for functional and aesthetic improvement. Although various non-surgical and surgical treatment strategies are available it is still difficult to improve excessive scarring. Thus, the importance of thorough knowledge of eyelid anatomy and heal­ing mechanisms along with appreciation of wound closure techniques like placing the sutures at natural cosmetic subunit junctions and along relaxed skin tension lines (RSTLs) in order to achieve scar camouflage and to ensure decreased tension on the wound cannot be more emphasised. Periorbital area should be tackled by the oculoplasty surgeons in view of their distinct anatomy and close proximity to the eye.Scars are commonly treated with a combination of non-surgical techniques, including watchful waiting, scar massage, pressure therapy, silicone gel sheeting, topical or intralesional injections, cryotherapy, laser therapy or radiotherapy. Surgical approaches include pincushioning debulking, direct scar excision, broken line closure techniques, scar lengthening procedures (Z plasty, V-Y/Y-V advancement) and scar excision with lid reconstruction. Mastery of this content is essential for consistent operative success. For good cosmetic and functional outcomes, scar revision techniques should be thoughtfully tailored to the individual and scar subtype.

A rare case of spinal myeloid sarcoma

Background: Myeloid sarcoma (MS), a rare extramedullary tumor composed of myeloid blast cells, is classified by the World Health Organization as a subtype of acute myeloid leukemia (AML). Isolated, primary, or nonleukemic MS has an incidence of 2/1,000,000 adults and constitutes only 0.7% of all AML cases. MS presentations vary widely, with spinal involvement being rare. Case Description: A-year-old male presented with interscapular pain radiating to the right upper arm/neck but was neurologically intact. Once diagnosed with isolated spinal MS, he underwent a surgical decompression followed by local irradiation, systemic chemotherapy, and bone marrow transplantation. Eight months postoperatively, however, he experienced a graft-versus-host rejection and required additional therapies. Conclusion: Establishing the diagnosis of MS is challenging and typically requires histological confirmation (i.e., the presence of myeloblasts and granulocytic cells). However, optimal treatment strategies remain elusive; despite radiation, chemotherapy, bone marrow transplant/other local therapies, the overall long-term prognosis for MS remains poor.

Mn3O4-MnOOH nanocomposites for the adsorption-based removal of nickel ions from wastewater.

The removal of nickel from wastewater is a significant environmental concern because of its potential hazards to environment. Adsorption is known as an efficient water treatment strategy and there is a growing interest in the development of new adsorbent materials providing rapid adsorption kinetics, cost-effectiveness, and high adsorption capacity. In this study, the feasibility of Mn3O4-MnOOH nanocomposites was evaluated as the adsorbent material for the removal of nickel ions from wastewater. The nanocomposites were prepared using a modified sonochemical method and characterized by XRD analysis and SEM images. Batch adsorption experiments were carried out under different experimental conditions obtained by varying solution pH, adsorbent amount, and contact period. Under the optimum adsorption conditions, the %RE value was recorded around 80% for 10mg/L Ni(II) ions. The adsorption characteristics were investigated with respect to adsorption isotherms and kinetics. Langmuir and Freundlich isotherm models were used to fit the adsorption data and the results indicated that adsorption of nickel ions onto nanocomposite could be complex and obey both monolayer adsorption and heterogeneous surface. Accordingly, maximum adsorption capacity of nanocomposites were calculated as 12.387mg/g. Research works comparing the kinetic models of pseudo-first-order, pseudo-second-order, and Elovich revealed that chemical sorption plays an important role as the rate-limiting step in the adsorption of nickel ions.

Artificial intelligence-enhanced biosurveillance for antimicrobial resistance in sub-Saharan Africa.

Antimicrobial resistance (AMR) remains a critical global health threat, with significant impacts on individuals and healthcare systems, particularly in low-income countries. By 2019, AMR was responsible for >4.9 million fatalities globally, and projections suggest this could rise to 10 million annually by 2050 without effective interventions. Sub-Saharan Africa (SSA) faces considerable challenges in managing AMR due to insufficient surveillance systems, resulting in fragmented data. Technological advancements, notably artificial intelligence (AI), offer promising avenues to enhance AMR biosurveillance. AI can improve the detection, tracking and prediction of resistant strains through advanced machine learning and deep learning algorithms, which analyze large datasets to identify resistance patterns and develop predictive models. AI's role in genomic analysis can pinpoint genetic markers and AMR determinants, aiding in precise treatment strategies. Despite the potential, SSA's implementation of AI in AMR surveillance is hindered by data scarcity, infrastructural limitations and ethical concerns. This review explores what is known about the integration and applicability of AI-enhanced biosurveillance methodologies in SSA, emphasizing the need for comprehensive data collection, interdisciplinary collaboration and the establishment of ethical frameworks. By leveraging AI, SSA can significantly enhance its AMR surveillance capabilities, ultimately improving public health outcomes.

Combination Nanodrug Delivery Systems Facilitate the Syncretism of Chemotherapy with Immunotherapy to Promote Cancer Treatment.

Cancer has emerged as a significant threat that gravely endanger human health. Anti-tumor immunotherapy has now emerged as an important treatment for cancer. However, immunosuppressive tumor microenvironment limits the antitumor immunity. The importance of the immune system in the cancer treatment process must be emphasized. Herein, two precision-targeted nanoparticles PD-L1@Cur-NPs and PD-1@AS-NPs are constructed for cancer treatment. PD-L1@Cur-NPs can precisely target tumor cells in vivo to eradicate tumor cells or induce them apoptosis. PD-1@AS-NPs can precisely target T cells in vivo to activate the T cell-mediated immune system and induce antitumor immune responses. Furthermore, these two nanoparticles have good synergistic effect and show stronger antitumor effect after combination. After treatment with the combination of two nanoparticles, the tumor volumes of C57BL/6 tumor-bearing mice are significantly reduced. Moreover, the percentage of CD8+T cells and CD4+T cells in the tumor significantly increased, and the percentage of regulatory T cells significantly decreased. The percentage of memory T cells and memory effector T cells in the spleen also significantly increased after treatment, suggesting that the antitumor immunity is activated after treatment. This study provides a new antitumor treatment strategy combining chemotherapy and immunotherapy, which has good application prospect.

A retrospective clinico epidemiological study of pattern of dermatosis involving trigeminal distribution in a tertiary care center

Trigeminal nerve is the principal sensory nerve of face. Many dermatological conditions known occur in relation to trigeminal nerve distribution clinically presenting as unilateral facial lesions with strict midline demarcation. To study the clinical pattern and epidemiological determinants of dermatoses along trigeminal nerve among the patients of both the sexes, involving all the age groups. Thirty two patients presenting with skin lesions along trigeminal nerve presenting to Dermatology department of a tertiary care center, Bangalore, Karnataka, are selected for the study. Study design is retrospective hospital record based study conducted from January 2023 to January 2024. In this study, out of 32 patients most common dermatoses along trigeminal nerve were infection of which herpes zoster was seen thirteen (40.62%) patients, followed by nevi (n=6, 18.75%), pigmentary disorders (n=5, 15.62%), vascular disorder (n=4, 12.5%) and auto inflammatory disorder (n=4, 12.5%) was seen. Most common branch affected was ophthalmic followed maxillary branch .Females were more common and mean age was 24 years. Small sample size and rare clinical cases are included Studies focusing on the pattern of dermatoses involving the trigeminal nerve contribute to the advancement of medical knowledge and facilitate the development of novel diagnostic techniques and therapeutic modalities. By elucidating the underlying pathophysiological mechanisms and identifying potential risk factors, research in this field can lead to the development of more effective treatment strategies tailored to the specific needs of patients.

Computed Tomography and Magnetic Resonance Imaging Features of Gracilis Myopathy in Dogs.

Gracilis myopathy is a well-recognized syndrome of weight-bearing gait abnormality; however, detailed description of computed tomography (CT) and magnetic resonance imaging (MRI) features of gracilis myopathy is lacking in the literature. This study aims to describe in detail CT and MRI features of gracilis myopathy. This is a retrospective study. Medical records of dogs with characteristic gait and available pelvic limb MRI or CT, presenting to four referral institutions, were reviewed. Seven cases with MRI (3/7) or CT (4/7) were included, all German Shepherd dogs. MRI findings in all cases included a well-defined, T1-/T2-/proton density-weighted hypointense band along the axial margin of the gracilis muscle, shorter affected muscles, thickening and T2W/STIR hyperintensity with contrast enhancement at the symphyseal tendon, and concurrent focal indentation of the axial border of the gracilis muscle. CT findings included a hyperattenuating band (4/4), single instances of contrast enhancement at the origin of the muscle, thickening of the tendon at the origin and insertion, and concurrent thickening at the musculotendinous muscle. CT and MRI can present advantages in correctly identifying the specific muscles affected within the gracilis-semitendinosus muscle complex. Both modalities can localize anatomically lesions in detail, for instance at the origin or insertion of the muscle, which could present advantages in novel treatment strategies for this condition.

Non-infectious mixed cryoglobulinemia as a new clinical presentation of mutation in the gene encoding coatomer subunit alpha: a case report of two adult sisters

Cryoglobulinemia is a rare disease characterized by the presence of cryoglobulins in the blood serum. It is usually caused by autoimmune, lymphoproliferative, or infectious factors. The pathogenesis of cryoglobulinemia is not well understood, therefore, genetic testing is very important. We present the case of two adult sisters with different clinical phenotypes of non-infectious cryoglobulinemic vasculitis associated with a rare genetic variant [(Hg38) 1:160323529 C>G, NP_004362.2:p.(Gly203Ala)]. One of the sisters suffered from essential mixed cryoglobulinemia, while the other suffered from cryoglobulinemia associated with systemic connective tissue disease. In both cases, genetic tests revealed a variant in the COPA gene, encoding coatomer subunit alpha. Mutations in the COPA gene are associated with COPA syndrome, an autoimmune interstitial lung, joint, and kidney monogenic disease, found mainly in children. Only 15 pathogenic COPA variants have been reported thus far which suggests that the full spectrum of disease manifestations remains unknown. Ours is the first report of the association of the COPA gene with non-infectious cryoglobulinemic vasculitis in adults. This unexpected finding may direct research into the pathogenesis of cryoglobulinemia and new treatment strategies for this rare disease.

Body composition as a prognostic factor in cholangiocarcinoma: a meta-analysis.

This investigation seeks to scrutinize the relationships between body composition metrics and the clinical outcomes observed in patients with cholangiocarcinoma (CCA). A comprehensive exploration was conducted across three prominent online databases: Embase, PubMed, and the Cochrane Library. This endeavor spanned the entirety of each database up to the cutoff date of September 29, 2023. To evaluate the quality of the included studies, the Newcastle-Ottawa scale was employed. This comprehensive analysis included a total of 26 articles with a combined patient cohort of 4398 individuals. The results demonstrated that CCA patients with low skeletal muscle index (SMI) had significantly inferior OS (HR: 1.93, p < 0.001) and RFS (HR: 2.02, p < 0.001), as well as a higher incidence of postoperative complications (OR: 1.69, 95% CI: 1.20-2.38, p < 0.001) compared to those with high SMI. The presence of sarcopenia in CCA patients was significantly related to poorer OS (HR: 1.96, p < 0.001) and RFS (HR: 2.05, p < 0.001), and a higher rate of postoperative complications (OR: 1.39, p = 0.049) in comparison to those without sarcopenia. Moreover, lower psoas muscle index (PMI) and myosteatosis were associated with shorter OS (PMI, HR: 1.56, p < 0.001; myosteatosis, HR: 1.49, p = 0.001) and RFS (PMI, HR: 2.16, p < 0.001; myosteatosis, HR: 1.35, p = 0.023). Our findings highlight incorporating body composition screening into clinical practice can help develop treatment strategies and optimize perioperative care, potentially improving patient outcomes.

Investigating the diagnostic and prognostic significance of genes related to fatty acid metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2-3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC. In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo. Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967-0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033-6.605, P < 0.001; multivariate Cox regression analysis: HR = 2.801%, 95% CI = 1.553-5.049, P < 0.001). Additionally, in vitro and in vivo experiments demonstrated that SLC22A1 inhibits HCC tumor development, suggesting it may be a potential therapeutic target for HCC. These findings indicate a considerable value of specific FA metabolism-related genes in the diagnostic and prognostic evaluation of HCC, which provide novel insights into the disease's management, as well as has potential implications for personalized treatment strategies. However, further investigation of the effects of these model genes on HCC is required.

An observational study of diagnostic hysterolaparoscopy for evaluation of infertility at a tertiary care hospital

Infertility is an illness recognised by the World Health Organisation (WHO) that refers to the inability to achieve a clinical pregnancy after engaging in regular, unprotected sexual intercourse for a period of 12 months or more. The incidence of primary infertility in India ranges from 3.9% to 16.8%. Hysteroscopy has emerged as a crucial technique for diagnosing infertility, providing a direct view of the uterine chamber to detect any possible abnormalities. The objective of this research is to analyse the use of diagnostic hysterolaparoscopy (DHL) in the evaluation of infertility. This research was a retrospective observational study that included 150 female patients who had a previous history of infertility. The study was done from May 2022 to September 2023. Information on the social and demographic characteristics of individuals and their medical history pertaining to infertility were collected by conducting interviews using a pre-tested, semi-structured questionnaire. Every participant took Dual-Hemisphere Language testing, and the gathered data were organised in Microsoft Excel. The significance threshold was established at 5% with a significance level of α = 0.05.: Out of the 150 patients that received DHL, 89 (59.33%) had primary infertility, whereas 61 (40.67%) had secondary infertility. Laparoscopy detected abnormalities in 35 (39.3%) of the individuals with primary infertility and 26 (42.6%) of the cases with secondary infertility. Abnormalities identified during hysteroscopy were 12 (13.4%) of the individuals with primary infertility and in 6 (9.83%) of the cases with secondary infertility. The prevalent abnormalities detected during hysteroscopy were uterine synechiae, fibroids, and uterine septa. The incidence of tubal obstructions was higher in the primary infertility group compared to the secondary infertility group.Diagnostic hysterolaparoscopy (DHL) is a very useful method for assessing infertility, namely in identifying adnexal adhesions, endometriosis, and uterine septa. In addition, DHL has the ability to detect several structural abnormalities in the uterus, fallopian tubes, and pelvis, which may assist in formulating suitable treatment strategies. So, both diagnostic and therapeutic intervention can be done at same sitting.