Metabonomics and proteomics were employed to investigate the mechanism of Yuzhi Zhixue Granules in treating polycystic ovary syndrome with insulin resistance(PCOS-IR). The disease model was established by feeding a high-fat diet and gavage of letrozole solution and it was then treated with different doses of Yuzhi Zhixue Granules. The therapeutic effect of Yuzhi Zhixue Granules was evaluated based on the body mass, homeostasis model assessment of insulin resistance and insulin sensitivity index, serum levels of adipokines, and histopathological changes of rats. Metabolomics and proteomics were employed to find the action pathways of Yuzhi Zhixue Granules. The results showed that Yuzhi Zhixue Granules reduced the body mass, improved the insulin sensitivity and aromatase activity, improved the levels of leptin, adiponectin and other adipokines, and alleviated insulin resistance, histopathological changes, and metabolic disorders in PCOS-IR rats. Metabolomics results revealed 14 metabolites with altered levels in the ovarian tissue, which were closely related to glutathione metabolism and pyruvate metabolism. Proteomics results showed that the therapeutic effect of Yuzhi Zhixue Granules was mainly related to the adipokine, adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), forkhead box protein O(FoxO), and mechanistic target of rapamycin(mTOR) signaling pathways. Western blot results showed that compared with the model group, Yuzhi Zhixue Granules treatment decreased the p-AMPK/AMPK and p-FoxO1/FoxO1 levels, increased the p-mTOR/mTOR level, and up-regulated the expression level of recombinant glucose transporter 4(GLUT4). Yuzhi Zhixue Granules can balance amino acid metabolism and pyruvate metabolism by regulating the AMPK/mTOR/FoxO/GLUT pathway to maintain the homeostasis of the ovarian environment and alleviate insulin resistance, thus treating PCOS-IR.
Animals ; Female ; Insulin Resistance ; Polycystic Ovary Syndrome/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Metabolomics ; Proteomics ; Rats, Sprague-Dawley ; Humans ; Ovary/metabolism* ; Signal Transduction/drug effects*

Electrical impedance tomography (EIT) is a new non-invasive functional imaging technology, which has the advantages of non-invasion, non-radiation, low cost, fast response, portability and visualization. In recent years, more and more studies have shown that EIT has great potential in the detection of lung diseases and has been applied to early diagnosis and treatment of some diseases. This paper introduced the basic principle of EIT, discussed the research and clinical application of EIT in the detection of acute respiratory distress syndrome, chronic obstructive pulmonary disease, pneumothorax and pulmonary embolism, and focused on the summary and introduction of indicators and functional images of EIT related to the detection of lung diseases. This review will help medical workers understand and use EIT, and promote the further development of EIT in lung diseases as well as other fields.
Humans ; Electric Impedance ; Tomography/methods* ; Lung Diseases/diagnosis* ; Pulmonary Disease, Chronic Obstructive/diagnosis* ; Pulmonary Embolism/diagnosis* ; Respiratory Distress Syndrome/diagnosis*

OBJECTIVE: To introduce the etiology and prevention of bone cement implantation syndrome (BCIS). METHODS: The literature about BCIS at home and abroad in recent years was extensively reviewed, and the incidence, clinical manifestations, etiology, and prevention of BCIS were summarized and analyzed. RESULTS: The clinical manifestations of BCIS are diverse. The etiology of BCIS is not completely clarified, and it may be related to circulating methyl methacrylate-mediated model, embolus-mediated model, histamine release and hypersensitivity response, complement activation and multimodal model. BCIS prevention begins with the identification of high-risk patients in preoperative evaluation and communication between surgeon and anesthesiologist about the choice of implant type, surgical procedure, and technique to minimize the risk of cardiovascular complications in high-risk patients with multiple or severe risk factors or comorbidities. Preoperative assessment and optimization of a patient's cardiovascular reserve is also critical to prevent BCIS. CONCLUSION BCIS is a possible complication after hip joint arthroplasty, and its pathogenesis needs to be further research in order to provide new ideas for prevention and treatment.
Humans ; Bone Cements/adverse effects* ; Postoperative Complications/etiology* ; Arthroplasty, Replacement, Hip/adverse effects* ; Risk Factors ; Syndrome ; Methylmethacrylate/adverse effects*

Polycystic ovary syndrome (PCOS) is the predominant cause of subfertility in reproductive-aged women; however, its pathophysiology remains unknown. Neurotensin (NTS) is a member of the gut-brain peptide family and is involved in ovulation; its relationship with PCOS is unclear. Here, we found that NTS expression in ovarian granulosa cells and follicular fluids was markedly decreased in patients with PCOS. In the in vitro culture of cumulus-oocyte complexes, the neurotensin receptor 1 (NTSR1) antagonist SR48692 blocked cumulus expansion and oocyte meiotic maturation by inhibiting metabolic cooperation and damaging the mitochondrial structure in oocytes and surrounding cumulus cells. Furthermore, the ERK1/2-early growth response 1 pathway was found to be a key downstream mediator of NTS/NTSR1 in the ovulatory process. Animal studies showed that in vivo injection of SR48692 in mice reduced ovulation efficiency and contributed to irregular estrus cycles and polycystic ovary morphology. By contrast, NTS partially ameliorated the ovarian abnormalities in mice with dehydroepiandrosterone-induced PCOS. Our findings highlighted the critical role of NTS reduction and consequent abnormal NTSR1 signaling in the ovulatory dysfunction of PCOS, suggesting a potential strategy for PCOS treatment.
Polycystic Ovary Syndrome/physiopathology* ; Female ; Animals ; Neurotensin/metabolism* ; Receptors, Neurotensin/antagonists & inhibitors* ; Mice ; Ovulation/drug effects* ; Humans ; Granulosa Cells/metabolism* ; Adult ; Oocytes/metabolism* ; MAP Kinase Signaling System ; Signal Transduction ; Follicular Fluid/metabolism* ; Disease Models, Animal ; Gonadotropin-Releasing Hormone/analogs & derivatives*

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

OBJECTIVE: To analyze the risk factors of hypophosphatemia in patients with acute respiratory distress syndrome (ARDS). METHODS: A retrospective case-control study was conducted. The clinical data of the patients with ARDS admitted to Yanbian University Affiliated Hospital from January 2018 to October 2022 were collected. According to the 1-day serum phosphorus level after intensive care unit (ICU) admission, the patients with normal (0.80-1.45 mmol/L) or elevated (> 1.45 mmol/L) serum phosphorus levels were included in the non-hypophosphatemia group, while those with phosphorus levels lower than 0.80 mmol/L were included in the hypophosphatemia group. The differences in the inflammatory indicators [neutrophils percentage (NEU%), neutrophil count (NEU), lymphocyte count (LYM), high-sensitivity C-reactive protein (hs-CRP)], proteins [total protein (TP), albumin (Alb), prealbumin (PA)], blood lactic acid (Lac), neutrophil/lymphocyte ratio (NLR), neutrophil/albumin ratio (NAR), and blood lactic acid/albumin ratio (L/A) at 1, 2, 4, 6 and 8 days after ICU admission were compared between the two groups. The partial correlation method was used to analyze the correlation between the 1-day serum phosphorus level after ICU admission and the above indicators. Multivariate Logistic regression analysis was adopted to explore the risk factors of hypophosphatemia in patients with ARDS. RESULTS: All 110 patients were enrolled in the final analysis, among which there were 56 cases in the hypophosphatemia group and 54 cases in the non-hypophosphatemia group. At 1 day and 2 days after ICU admission, NEU% in the hypophosphatemia group were significantly higher than those in the non-hypophosphatemia group (1 day: 0.87±0.08 vs. 0.82±0.12, 2 days: 0.87±0.05 vs. 0.83±0.11, both P < 0.05). As the ICU admission time prolonged, LYM in the hypophosphatemia group was basically on the rise, and NEU%, hs-CRP, and NLR were first decreased and then increased. At 1 day after ICU admission, TP, Alb and PA in the hypophosphatemia group were significantly lower than those in the non-hypophosphatemia group [TP (g/L): 52.96±8.42 vs. 56.47±8.36, Alb (g/L): 29.73±5.83 vs. 33.08±7.35, PA (g/L): 69.95±50.72 vs. 121.50±82.42, all P < 0.05]. As the ICU admission time prolonged, TP and Alb in the hypophosphatemia group were basically showed a trend of first decreasing and then increasing, but at 8 days, Alb was still lower than that at 1 day, and PA basically showed an upward trend. In the non-hypophosphatemia group, the change trends of TP and Alb were consistent with those in the hypophosphatemia group. Lac and L/A both showed a downward trend in the two groups. Partial correlation analysis showed that 1-day serum phosphorus level after ICU admission was significantly negatively correlated with NEU% and hs-CRP (r value was -0.229 and -0.286, respectively, both P < 0.05), and significantly positively correlated with LYM and PA (r value was 0.231 and 0.311, respectively, both P < 0.05). Multivariate Logistic regression analysis showed that 1-day NEU% [odds ratio (OR) = 0.932, 95% confidence interval (95%CI) was 0.873-0.996, P = 0.038] and Alb (OR = 1.167, 95%CI was 1.040-1.308, P = 0.008) were the independent risk factors for hypophosphatemia in ARDS patients. CONCLUSION NEU% and Alb at 1 day after ICU admission are independent risk factors for hypophosphatemia in patients with ARDS.
Humans ; Hypophosphatemia/etiology* ; Respiratory Distress Syndrome/blood* ; Risk Factors ; Retrospective Studies ; Case-Control Studies ; Intensive Care Units ; Male ; Female ; Phosphorus/blood* ; Middle Aged ; Neutrophils ; Aged ; C-Reactive Protein

BACKGROUND

Down syndrome or trisomy 21, the most common chromosomal disorder, results from the presence of a third copy of chromosome 21 and manifests as mild to moderate intellectual disability, growth retardation, congenital heart defects, gastrointestinal abnormalities, and characteristic facial features. Several methods have been used to screen for Down syndrome in the prenatal period, such as ultrasound, biomarkers, cell-free DNA testing, and combinations of these tests. A positive result from one or more of these screening tests signals the need for confirmatory karyotyping to clinch the diagnosis. Ultrasound between 11 to 14 weeks of gestation can evaluate nuchal translucency (NT) to screen for Down syndrome. During the second trimester, a triple or quadruple test can also be performed alone or in addition to NT to quantify Down syndrome risk. In limited resource settings however, only the measurement of NT via ultrasound can be performed since biomarker tests are either unavailable or inaccessible. While the diagnostic performance of NT measurement alone has been investigated in several observational studies, there is no consensus on its performance as a sole test to screen for Down syndrome.

To determine the diagnostic performance of NT during prenatal first-trimester ultrasound as a screening test for Down syndrome.

We performed a systematic search on the PubMed, ProQuest, and Cochrane Library databases for recent systematic reviews and meta-analyses that addressed the objective. The existing reviews found were then independently appraised by the two reviewers with the AMSTAR-2 checklist. To update the existing reviews, a systematic search was done in the same databases to identify additional primary diagnostic studies, which were appraised using the QUADAS-2 tool. Random-effects univariate meta-analysis and summary receiving operator curve (HSROC) analysis for the outcomes were performed using Review Manager version 5.4 and R version 4.2.2, respectively. Subgroup analysis was performed by stratifying the baseline risk of mothers for fetal anomaly as low- or high-risk. Highrisk mothers were defined as women with risk factors such as advanced age, positive serum screen, presence of other ultrasound anomalies, and history of previous fetus with anomaly.

We found 22 cohort studies (n=225,846) of women at low-risk for fetal anomaly. The pooled sensitivity was 67.8% (95% CI: 61.4%-73.6%, I2=70.4%) and specificity was 96.3% (95% CI: 95.5%-96.9%, I2=96.7%). For low-risk women, the overall certainty of evidence was low, due to different modes of verification and heterogeneity not completely explained by variability in baseline risk or cut-points. Seven studies (n=9,197) were on high-risk women. The pooled sensitivity was 62.2% (95% CI: 54.1%-69.7%, I2=38.8%) and specificity was 96.5% (95% CI: 93.6%-98.1%, I2=95.5%). For women at high-risk, the evidence was rated as moderate due to differential verification.

Our analysis showed that NT measured through first-trimester ultrasound is specific for Down syndrome but has low sensitivity. Despite this, it is a useful screening test for Down syndrome in low-resource settings where other strategies may not be available or accessible. Furthermore, interpretation of NT results must take into consideration its limited sensitivity as this may lead to missed cases.

Neuropsychiatric SLE (NPSLE) comprises the neurologic and psychiatric syndromes observed in patients with SLE after exclusion of other causes. The diagnosis of NPSLE is challenging due to diverse clinical manifestations and absence of laboratory or radiologic biomarkers.

We present the case of a patient with SLE with a chronic isolated seizure and was successfully managed with antiepileptic medication and high-dose corticosteroids.

Seizures may occur as an isolated manifestation of an SLE flare. Ischemic and inflammatory causes of seizure may coexist in active lupus and both should be considered in managing patients. A prompt and holistic workup to rule out metabolic, infectious, and structural neural causes and lupus disease activity of seizures is prudent for patients with SLE.

Posterior fossa malformations are rare cyst-like pathologies of the central nervous system. Outcomes of patients with these conditions are largely documented in fetal or early childhood studies as most cases are non-compatible with life. Also, different schemes to categorize these occurrences have been proposed. One classification puts forth that the entities are a continuum of pathologies, called the Dandy Walker Complex, wherein Mega Cisterna Magna is the most benign to Dandy Walker Malformation as the most severe form. We report the first case of a patient with a mixed presentation of Mega Cisterna Magna having extracranial manifestations of Dandy Walker Malformation reaching her adult years. The patient is a 26-year-old female who was apparently well until she presented with recurrent headache and seizure episodes of 2-year duration. She had an unremarkable birth and childhood history, apart from learning difficulties in school. In her adult years, she gave birth to an infant with multiple physical anomalies. She has a maternal uncle with abnormal facie and intellectual disability. Physical examination of the patient exhibited a bulging occiput, hypertelorism, down-slanting palpebral fissures, large globular nose, large ear lobules, high arched palate, and clinodactyly. Neurologic examination was unremarkable. Magnetic resonance imaging confirmed Mega Cisterna Magna and was deemed non-surgical. She remained seizure-free during admission as well as on followup, maintained on Phenytoin. The existence of a Dandy-Walker continuum is still debated, as the link among the disease entities are yet to be established using developmental or genetic studies. This case, however, supports the Dandy-Walker Complex classification by demonstrating a rare combination of Mega Cisterna Magna with features of Dandy-Walker Malformation in an adult. This can contribute to disease definition and eventually to the discovery of the pathobiological mechanisms of posterior fossa cysts, and to appropriate diagnosis and management.

BACKGROUND AND OBJECTIVES

A mounting evidence links dysregulated immune response to cases of fatal pneumonia seen in COVID-19 infection. We aimed to validate the COVID-19-associated Hyperinflammatory Syndrome (cHIS) score, a novel clinical tool devised to identify those at risk for adverse outcomes, in a local population and investigate the relationship of cHIS score taken at admission and the risk of mortality and the need of mechanical ventilation.

This retrospective cohort study analyzed the sociodemographic, clinical, and laboratory data of 1,881 COVID-19 patients admitted at a tertiary hospital in Davao City, Philippines from January to December 2021. We calculated the cHIS score, composed of six clinical and laboratory criteria from admission, and used multivariate logistic regression to determine the risk of mortality and need of mechanical ventilation.

The cHIS score taken at admission, regardless of cut-off value, was a significant predictor of mortality (OR 0.979 [99% CI 0.894-1.064]) and need of mechanical ventilation (OR 0.586 [99% CI 0.4975-0.6745]). Using the Youden Index, a cut-off cHIS score of 3 or more was a better predictor of mortality (sensitivity, 88.59%; specificity, 71.72%), and a cut-off score of 2 or more was a better predictor of need of mechanical ventilation (sensitivity, 84.02%; specificity, 70.82%) than other cutoff cHIS scores.

Among COVID-19 patients, the cHIS score at admission correlated with the risk of mortality and the need of mechanical ventilation. Cutoff scores of 3 and 2 had the optimal sensitivities and specificities to predict the risk of mortality and the need of mechanical ventilation, respectively.