Main Clinical Manifestations Research Articles

Candida parapsilosis complex in the clinical setting.

Representatives of the Candida parapsilosis complex are important yeast species causing human infections, including candidaemia as one of the leading diseases. This complex comprises C. parapsilosis, Candida orthopsilosis and Candida metapsilosis, and causes a wide range of clinical presentations from colonization to superficial and disseminated infections with a high prevalence in preterm-born infants and the potential to cause outbreaks in hospital settings. Compared with other Candida species, the C. parapsilosis complex shows high minimal inhibitory concentrations for echinocandin drugs due to a naturally occurring FKS1 polymorphism. The emergence of clonal outbreaks of strains with resistance to commonly used antifungals, such as fluconazole, is causing concern. In this Review, we present the latest medical data covering epidemiology, diagnosis, resistance and current treatment approaches for the C. parapsilosis complex. We describe its main clinical manifestations in adults and children and highlight new treatment options. We compare the three sister species, examining key elements of microbiology and clinical characteristics, including the population at risk, disease manifestation and colonization status. Finally, we provide a comprehensive resource for clinicians and researchers focusing on Candida species infections and the C. parapsilosis complex, aiming to bridge the emerging translational knowledge and future therapeutic challenges associated with this human pathogen.

Protein S Defficiency and The Mechanism of Protein S in Hemostasis and Atherosclerosis

Protein S (PS) is Vitamin K dependant protein which plays a role in regulating the blood clotting process in the body. Protein S deficiency is explained as a condition characterized by reduced levels of protein S in the serum so that it makes the blood clot too easily. The purpose of this literature review is to give an update of protein S defficiency and the mechanism of protein s in hemostasis and atherosclerosis based on publish literature reference from various database. Protein S plays important role in hemostasis by regulating blood cloth process in the initiation phase of the extrinsic pathway as a TFPI cofactor or in the propagation phase, namely as an APC cofactor and independent activity of TFPIα and APC. Protein S deficiency is known to be associated with the occurrence of atherosclerosis via the Tyro3-Axl-Mer (TAM) receptor. The main clinical manifestations of the majority of patients with heterozygous mutations in the protein S (PROS1) gene are deep vein thrombosis (DVT) and pulmonary embolism that precipitate by VTE. Administration of anticoagulant drugs such as heparin in the form of low-molecular-weight heparin (LMWH) or unfractionated heparin, vitamin K antagonists (VKA), namely warfarin, or direct oral anticoagulants (DOACs) can be selected as a management of protein S deficiency with VTE. Protein S has a central role in the coagulation prosses and its deficiency associated with atherosclerotic conditions.

Selective IgM Deficiency: Evidence, Controversies, and Gaps.

Selective Immunoglobulin M deficiency (SIgMD) has been recently included in the inborn errors of immunity (IEI) classification by the International Union of Immunological Societies Expert Committee. The understanding of SIgMD is still extremely limited, especially so in cases of SIgMD in the pediatric population. The epidemiology of SIgMD in the pediatric population is still unknown. The pathogenesis of SIgMD remains elusive, and thus far no genetic nor molecular basis has been clearly established as a definitive cause of this primary immunodeficiency. Recurrent respiratory infections represent the main clinical manifestations in children, followed by allergic and autoimmune diseases. No conclusive data on the correct therapeutic management of SIgMD are available. Although, for most SIgMD patients, Ig replacement therapy is not required, it may be recommended for patients with significantly associated antibody deficiency and recurrent or severe infections. Prophylactic antibiotics and the prompt treatment of febrile illness are crucial. There is insufficient evidence on the prognosis of this condition. Therefore, further studies are required to define the disease trajectories and to increase our understanding of the molecular mechanisms underlying SIgMD in order to facilitate a better clinical, immunological, and prognostic characterization of the condition and develop tailored therapeutic management strategies.

Clinical and pathological characteristics of acute kidney injury caused by diquat poisoning

Introduction: Diquat poisoning leads to kidney injury, hepatotoxicity, rhabdomyolysis, gastrointestinal hemorrhage, and respiratory failure. Diquat has high mortality and no specific antidote. The pathology of acute kidney injury caused by diquat poisoning has been mainly investigated in animal studies and autopsies, and typically shows renal tubular necrosis. To our knowledge, antemortem renal biopsy has not been reported in humans. Case reports: Two males and one female presented following deliberate diquat self-poisoning. Their main clinical manifestations were abdominal pain, nausea, and emesis. All developed acute kidney injury. Kidney biopsy was performed in two cases which showed acute tubular necrosis with renal interstitial edema and multifocal inflammatory cell infiltration. Treatments given included gastric lavage, catharsis, early hemoperfusion combined with continuous kidney replacement therapy or hemodialysis, administration of glucocorticoids, and antioxidant therapy. All patients survived. Discussion: Despite potentially lethal ingestions three patients survived oral diquat poisoning with intensive supportive care. No clear relationship can be made between any of the therapies given and patient outcome. Conclusions: Kidney biopsy in these patients confirmed proximal renal tubular injury was the major pathological finding although interstitial injury was also present. The role of therapies that address renal pathology requires further study.

Non-muscle myosin heavy chain 9 gene-related disorders with thrombocytopenia: report of two pedigrees and literature review

Objective: To summarize the clinical characteristics and gene variants of 2 pedigrees of non-muscle myosin heavy chain 9 related diseases (MYH9-RD) in children. Methods: The basic information, clinical features, gene variants and laboratory tests of MYH9-RD patients from 2 pedigrees confirmed in the First Affiliated Hospital of Zhengzhou University in November 2021 and July 2022 were analyzed retrospectively. "Non-muscle myosin heavy chain 9 related disease" "MYH9" and "children" were used as key words to search at Pubmed database, CNKI and Wanfang database up to February 2023. The MYH9-RD gene variant spectrum and clinical data were analyzed and summarized. Results: Proband 1 (male, 11 years old) sought medical attention due to epistaxis, the eldest sister and second sister of proband 1 only showed excessive menstrual bleeding, the skin and mucous membrane of the their mother were prone to ecchymosis after bumping, the uncle of proband 1 had kidney damage, and the maternal grandmother and maternal great-grandmother of proband 1 had a history of cataracts. There were 7 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that the proband 1 MYH9 gene had c.279C>G (p.N93K) missense variant, and family verification analysis showed that the variant was inherited from the mother. A total of 4 patients including proband 1 and family members were diagnosed with MYH9-RD. The proband 2 (female, 1 year old) sought medical attention duo to fever and cough, and the father's physical examination revealed thrombocytopenia. There were 2 cases of phenotypic abnormalities in this pedigree. High-throughput sequencing showed that there was a c.4270G>A (p.D1424N) missense variant in the proband 2 MYH9 gene, and family verification analysis showed that the variant was inherited from the father. A total of 2 patients including proband 2 and his father were diagnosed with MYH9-RD. A total of 99 articles were retrieved, including 32 domestic literatures and 67 foreign literatures. The MYH9-RD cases totaled 149 pedigrees and 197 sporadic patients, including 2 pedigrees in our study. There were 101 cases with complete clinical data, including 62 sporadic cases and 39 pedigrees. There were 56 males and 45 females, with an average age of 6.9 years old. The main clinical manifestations were thrombocytopenia, skin ecchymosis, and epistaxis. Most patients didn't receive special treatment after diagnosis. Six English literatures related to MYH9-RD caused by c.279C>G mutation in MYH9 gene were retrieved. Italy reported the highest number of cases (3 cases). Twelve literatures related to MYH9-RD caused by c.4270G>A mutation in MYH9 gene were retrieved. China reported the highest number of cases (9 cases). Conclusions: The clinical manifestations of patients in the MYH9-RD pedigrees varied greatly. MYH9 gene c.279C>G and c.4270G>A mutations are the cause of MYH9-RD.

Diagnosis and treatment of malignant mesothelioma of the tunica vaginalis testis: a series of 7 cases

Objective: To investigate the clinical features, diagnosis, prognosis of malignant mesothelioma of the tunica vaginalis testis (MMTVT). Methods: The clinicopathological data of 7 patients with MMTVT who treated at Sun Yat-sen University Cancer Center between January 2010 and October 2022 were retrospectively reviewed. Cases were first diagnosed at (M (IQR)) 49 (23) years old (range: 27 to 64 years old). The main clinical manifestations were scrotal enlargement (7 cases) and hydrocele (2 cases). Results: Three patients underwent radical orchiectomy as initial treatment, 2 cases underwent hydrocelectomy due to diagnosis of hydrocele, followed by radical orchiectomy at Sun Yat-sen University Cancer Center, and 2 cases underwent transscrotal orchiectomy. Common tumor markers of testicular cancer were not significantly elevated in MMTVT. The expression of tumor PD-L1 was positive in 2 out of the 3 cases. One patient received adjuvant chemotherapy and 2 patients received first-line chemotherapy after tumor recurrence. Chemotherapy regimens used include cisplatin+pemetrexed. Up to October 2022, 3 cases relapsed, of which 2 cases died. The median overall survival was 35 months (range: 4 to 87 months) and the median progression-free survival was 6 months (range: 2 to 87 months). Conclusions: MMTVT at early stage should be treated with early radical orchiectomy and followed up closely after surgery. The cisplatin+pemetrexed regimen is a common option for the treatment of metastatic MMTVT, while whether immune checkpoint inhibitors could serve as a second-line treatment option deserves further research.

The Clinical Characteristics, Diagnostic Methods, Treatment, and Outcomes of Listeria monocytogenes Meningoencephalitis: A Case Series Study from China.

Listeria monocytogenes meningoencephalitis (LMM) is a rare but dangerous infection of the nervous system. This study intends to summarize and discuss the clinical features, diagnostic methods, treatment, and outcomes. LMM patients treated in the First Affiliated Hospital of Zhengzhou University from June 2013 to December 2022 were retrospectively studied. The clinical data, magnetic resonance imaging (MRI), biochemical and hematological parameters, pathogen tests, treatments, and outcomes information were collected and summarized. Ten LMM patients were enrolled in this study. Three were female and seven were male, with a mean age of 54.5 years old. Seven (70%) of the patients had chronic conditions that either affected the liver (1 case), heart (1 case), or immune system (5 cases). The main clinical manifestations were fever (100%), headache, (60%), and disturbance of consciousness (60%). Out of the nine patients taken MRI, enhanced magnetic resonance imaging was observed with cerebral parenchyma and meningeal enhancement in 3 patients, whereas six patients showed non-specific abnormal signals and brain edema. Seven (70%) patients were positive for L. monocytogenes by bacterial culture and five patients were positive by further next-generation sequencing (NGS) test in CSF. All patients were treated with antibiotics based on antibiotic sensitivity tests or experience, with seven (70%) improved but three (30%) died within one month. LMM patients have a high mortality rate. Considering the time and reliability of NGS reports, it would be better to identify L. monocytogenes infection in the CSF than bacterial culture. While, after diagnosis, giving timely and appropriate antibiotics would still be a challenge to achieve good outcomes.

A Case Report of Turner Syndrome and Literature Review

Turner syndrome (TS), also known as congenital dysplasia of ovary syndrome, is the most common female chromosomal abnormality, and the incidence of live birth girls is 1/2 000 ~ 1/2 500. The main clinical manifestations of Turner syndrome are spinal trunk abnormality, growth retardation, sexual dysplasia and special physical characteristics, and abnormal sex hormone, abnormal growth hormone, dyslipidemia, etc. This article summarized and analyzed the clinical characteristics and test results of a child with Turner syndrome, combined with literature review, in order to improve the understanding of Turner syndrome and clinical diagnosis and treatment.

The CADA-MRIT: An MRI Inventory Tool for Evaluating Cerebral Lesions in CADASIL Across Cohorts.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent genetic cerebrovascular disease. The clinical aspects of the disease in relation to the various types of lesions on MRI vary widely not only within families but also between different cohorts reported worldwide. Many limitations prevent comparison of imaging data obtained with different scanners and sequences in different patient cohorts. We aimed to develop and validate a simple tool to inventory quickly the key MRI features in CADASIL to compare imaging data across different populations. The Inventory Tool (CADA-MRIT) was designed by consensus after repeated expert meetings. It consists of 11 imaging items to assess periventricular, deep, and superficial white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMB), centrum semiovale and basal ganglia dilated perivascular spaces (dPVS), superficial and deep atrophy, large infarcts, and macrobleeds. The reliability, clinical relevance, and time-effectiveness of CADA-MRIT were assessed using data from 3 independent patient cohorts. Imaging data from 671 patients with CADASIL (440 from France, 119 from Germany, and 112 from Taiwan) were analyzed. Their mean age was 53.4 ± 12.2 years, 54.5% were women, 56.2% had stroke, and 31.1% had migraine with aura. Any lacune was present in at least 70% of individuals, whereas CMB occurred in 83% of patients from the Asian cohort and in only 35% of European patients. CADA-MRIT scores obtained for WMH, CMB, and dPVS were comparable regardless of the scanner or sequence used (weighted κ > 0.60). Intrarater and interrater agreements were from good to very good (weighted κ > 0.60). Global WMH and atrophy scores correlated strongly with accurate volumetric quantification of WMH or brain parenchymal fraction (Pearson r > 0.60). Different imaging scores were significantly associated with the main clinical manifestations of the disease. The time for evaluating 1 patient was approximately 2-3 minutes. The CADA-MRIT is an easy-to-use tool for analyzing and comparing the most frequent MRI lesions of CADASIL across different populations. This instrument is reliable. It can be used with different imaging sequences or scanners. It also provides clinically relevant scores in a very short time for completion.

The role of α-synuclein in Parkinson disease

Parkinson disease (PD) was a common insidious neurodegenerative disorder that occurs in middle-aged and elderly people, where the dopaminergic neurons in the midbrain substantia nigra (Dopamine, DA) die over time and the main clinical manifestations are resting tremor, motor bradykinesia, rigidity and eventual inability to control motor functions [1] The specific pathogenesis of PD was complex and not yet clear, but misfolding and aggregation of α-synuclein (α-Syn) is considered to be the hallmark of PD. Since early diagnosis of the disease is difficult, this review summarizes how α-Syn is involved in several aspects into neuronal function and recent advances in targeting α-Syn for PD, providing a theoretical basis for subsequent treatment of PD.

Establishment of human-induced pluripotent stem cell GZHMCi0011-A from peripheral blood mononuclear cells from a volunteer with 14/63 CAG repeats of the ATXN3 mutation

Spinocerebellar ataxia type 3 (SCA3) is a genetic degeneration disease of the nervous system with ataxia as the main clinical manifestation, and the most frequent subtype of SCA3 is known to be caused by CAG repeat expansions of more than 55 units in ATXN3. In this study, we used peripheral blood mononuclear cells (PBMCs) from a volunteer with 14/63 CAG repeats in ATXN3 to generate induced pluripotent stem cells (iPSCs), which will be a good model for studying SCA3.

The Current Role of Cardiopulmonary Exercise Test in the Diagnosis and Management of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease with a poor prognosis if left untreated. Despite remarkable achievements in understanding disease pathophysiology, specific treatments, and therapeutic strategies, we are still far from a definitive cure for the disease, and numerous evidences have underlined the importance of early diagnosis and treatment to improve the prognosis. Cardiopulmonary exercise testing (CPET) is the gold standard for assessing functional capacity and evaluating the pathophysiological mechanisms underlying exercise limitation. As effort dyspnea is the earliest and one of the main clinical manifestations of PAH, CPET has been shown to provide valid support in early detection, differential diagnosis, and prognostic stratification of PAH patients, being a useful tool in both the first approach to patients and follow-up. The purpose of this review is to present the current applications of CPET in pulmonary hypertension and to propose possible future utilization to be further investigated.

Clinical course features of atypical demyelinating optic neuritis: case series

Optic neuritis (ON) can often occur at the onset of a demyelinating autoimmune CNS disease or as one of its clinical manifestations. The introduction of novel laboratory techniques, technical advances in magnetic resonance imaging (MRI), electrophysiologic studies, and ocular imaging have significantly expanded the spectrum of autoimmune optic neuropathies. Identification of different forms of ON based on clinical and instrumental data can lead to early diagnosis of the underlying neurologic disorder. According to current guidelines, one can distinguish between typical ON, which are mainly associated with multiple sclerosis (MS), and atypical ON, which are the main clinical manifestation of neuromyelitis optica spectrum disorders (NMOSD) and diseases associated with myelin oligodendrocyte glycoprotein antibodies (MOGAD). In this paper, we present four clinical cases of atypical ON at the onset of NMOSD and MOGAD and illustrate the high diagnostic value of a multidisciplinary approach.

CT Findings of Undifferentiated Pancreatic Cancer With Osteoclast-Like Giant Cells: A Case Series from a Single Center's Experience With 10 Cases.

Little is known about the imaging features of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) because of its extremely low incidence. To improve the diagnostic accuracy of this tumor, 10 UCOGCP cases with confirmed histopathology were collected and their clinical and image data features were analyzed. We found that the median age of our study was 61 years (50-76 years in range) and the main clinical manifestations were nonspecific abdominal pain. There were some differences in the degree of enhancement and computed tomography (CT) features between the tumor located at the head and body or tail of the pancreas. Perhaps these subtle imaging findings can provide valuable diagnostic information.

Characteristics and risk factors for colorectal polyps among children in an urban area of Wenzhou, China: a retrospective case control study

BackgroundScarce evidence exists on pediatric colorectal polyp risk factors. This study explored the clinical manifestations, morphological and pathological characteristics of, and risk factors for pediatric colorectal polyps.MethodsThis retrospective case-control study included children who received colonoscopy, divided into a colorectal polyp group and a normal control group based on colonoscopy results. The risk factors for colorectal polyps in children were analyzed through logistic regression analysis.ResultsThe mean age of children with polyps was 6.77 ± 3.44 years. Polyps were detected predominantly in males (72.9%); hematochezia was the primary clinical manifestation (80.25%). Most polyps were juvenile (88.9%) and solitary (87.7%); 50.6% were located in the rectosigmoid area. Univariate analysis showed that gender (P = 0.037), age (P < 0.001), family aggregation (P < 0.001), specific immunoglobulin E (sIgE) (P < 0.001), platelet count (P = 0.001), aspartate aminotransferase (AST) (P = 0.016), meat intake (P = 0.010), and vegetable intake (P < 0.001) were significantly associated with colorectal polyps. Age ≤ 6 years (3–6 years: OR: 26.601, 95% CI: 3.761–160.910; < 3 years: OR: 22.678, 95% CI: 1.873–274.535), positive family aggregation (OR: 3.540, 95% CI: 1.177–10.643), positive sIgE (OR:2.263, 95% CI: 1.076–4.761), and higher meat intake (OR:1.046, 95% CI: 1.029–1.063) were risk factors for pediatric colorectal polyps in logistic regression analysis. Higher vegetable intake (OR: 0.993, 95% CI: 0.986–1.000) was a protective factor against pediatric colorectal polyps. The area under the curve (AUC) of meat intake in the receiver operating characteristic (ROC) curve analysis for predicting colorectal polyps was 0.607; the best cut-off value was 92.14 g/d (P = 0.010, 95% CI: 0.527–0.687). The meat and vegetable intake combination AUC in predicting pediatric colorectal polyps was 0.781 (P < 0.001, 95% CI: 0.718–0.845).ConclusionsJuvenile, solitary, and located in the rectosigmoid region polyps are most common in children. Hematochezia is the main clinical manifestation. Most polyps were, but multiple and proximally located polyps were also detected. Age ≤ 6 years, especially 3–6 years, positive family aggregation, positive sIgE, and higher meat intake are risk factors for pediatric colorectal polyps. A higher vegetable intake is a protective factor.

Risk factors of deep vein thrombosis in children with osteomyelitis

Objective To investigate the risk factors for deep vein thrombosis (DVT) in children with osteomyelitis and provide diagnostic and treatment strategies for the prevention, early detection and treatment of DVT. Study design The clinical data of nine children diagnosed with osteomyelitis and DVT between July 2012 and March 2021 were collected at our hospital, including age, sex, clinical manifestations, body temperature, coagulation function and other data, as well as the clinical data of 27 children diagnosed with osteomyelitis without DVT during the same period. Thirty-six children were divided into thrombus and thrombus-free groups. The clinical characteristics and risk factors for DVT in children with osteomyelitis were analysed. Results Among the 36 children in this study, nine cases of thrombus formation mainly occurred in the femoral vein, popliteal vein and iliac vein, all near the infection site. The main clinical manifestations were lower extremity pain, swelling and pulmonary embolism in three cases. Among them, intensive care unit (ICU) admission, sepsis, higher D-dimer, higher body temperature during hospitalization, and pathogen culture showed that methicillin-resistant Staphylococcus aureus (MRSA) was associated with DVT. MRSA was the independent risk factor for DVT. Conclusions Admission to ICU, sepsis, higher D-dimer, higher body temperature during hospitalization, and MRSA are risk factors for thrombosis. MRSA is the independent risk factor for DVT. For patients with related risk factors, timely ultrasound examination of the infected site should be considered to achieve early detection and treatment.

PolyQ Database-an integrated database onpolyglutamine diseases.

Polyglutamine (polyQ) diseases are neurodegenerative disorders caused by abnormally expanded Cytosine, Adenine, Guanine (CAG) triplet repeat sequences in the coding region of otherwise unrelated genes. Until now, nine different polyQ diseases have been described: Huntington's disease, dentatorubral-pallidoluysian atrophy, spinal and bulbar muscular atrophy and six types of spinocerebellar ataxias-1, 2, 3, 6, 7 and 17. The pathogenic expansion translates into an aberrant tract of glutamines in the encoded proteins, compromising several cellular functions and biological processes. There is currently no cure available for the progressive neurodegenerative disorders caused by the ensuing cytotoxic alterations. Although each disease is considered rare, polyQ diseases constitute the largest group of monogenic neurodegenerative disorders. Information about these disorders is scattered among several books, articles and general databases, hindering exploration by students and researchers, but also by patients and their families. Therefore, we aimed to develop a free online database to fill this gap, by centralizing relevant available information. The PolyQ Database is a platform that focuses on all nine polyQ diseases and offers information about topics that are pertinent for scientists, clinicians and the general public, including epidemiology, the characteristics of the causative genes and the codified proteins, the pathophysiology of the diseases and the main clinical manifestations. The database is available at https://polyq.pt/, and it is the first of its kind, focusing exclusively on this group of rare diseases. The database was conceived to be continuously updated and allow incorporation and dissemination of the latest information on polyQ diseases.

Papilledema and Chiari I in childhood: case report

Introduction: Chiari malformation type I (CM-I) is a condition characterized by an abnormal craniocervical transition whose main finding is cerebellar tonsillar ectopia of &gt; 5 mm below the foramen magnum. The main clinical manifestations are occipital headache, truncal ataxia, corticospinal tract dysfunctions, and scoliosis.&#x0D; Objective: The scope of this article is to report a rare case of papilledema and visual impairment in a child diagnosed with CM-I.&#x0D; Methods/case presentation: Presentation of the case of an 8-year-old child with difficulty in performing school activities due to visual blurring in the 3 days prior to hospitalization. She was taken by her parents to the ophthalmologist who identified bilateral papilledema and was urgently referred to the pediatric emergency unit. She underwent magnetic resonance imaging of the brain and CM-I was identified. She underwent urgent surgical posterior cranial fossa decompression and progressed to complete visual improvement, confirmed by ophthalmological examination.&#x0D; Conclusion: Papilledema may be the initial clinical manifestation of CM-I in children and urgent surgical decompression of the posterior cranial fossa may prevent or even reverse the visual impairment.

Fluoride-induced osteoporosis via interfering with the RANKL/RANK/OPG pathway in ovariectomized rats: Oophorectomy shifted skeletal fluorosis from osteosclerosis to osteoporosis

Osteosclerosis and osteoporosis are the two main clinical manifestations of skeletal fluorosis. However, the reasons for the different clinical manifestations are unclear. In this study, we established the fluoride (F) -exposed ovariectomized (OVX) and non-OVX rat models to assess the potential role of ovarian function loss in osteosclerosis and osteoporosis. Micro-CT scanning showed that excessive F significantly induced a high bone mass in non-OVX rats. In contrast, a low bone mass manifestation was presented in OVX F-exposed rats. Also, a prominent feature of increasing trabecular connectivity, collagen area, growth plate thickness, and reduced trabecular space was found by histopathological morphology in non-OVX F-exposed rats; an opposite result was observed in OVX F-exposed. These alterations indicated ovariectomy was a vital factor leading to osteosclerosis or osteoporosis in skeletal fluorosis. Furthermore, levels of bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRAP) increased, combined with the increasing osteoclasts number, showing a sign of high bone turnover in both OVX and non-OVX F-exposed rats. Mechanistically, oophorectomy considerably activated the RANKL/RANK/OPG signaling pathway. Meanwhile, it was discovered that upregulated NF-κB positively facilitated the accumulation of nuclear factor of activated T-cells 1 (NFATC1), significantly promoting osteoclast differentiation. To sum up, this study greatly enriched the causes of clinical skeletal fluorosis and provided a new perspective for studying the pathogenesis of skeletal fluorosis.

Clinical characteristics of the cardiovascular system involvement in various variants of ankylosing spondylitis

Inflammatory and degenerative spinal diseases are one of the pressing problems of modern rheumatology due to the high prevalence, frequent incidence of diseases of young and middle-aged men, frequent lesions of internal organs, early disability of patients, socio-economic damage caused to the patient and society [1]. Since 1892, when V.M.Bekhterev described the main clinical manifestations of the disease and suggested that it should be singled out as a separate nosological form, researchers from the leading countries of the world have achieved certain success in studying its nature, mechanisms of development, as well as treatment and rehabilitation of patients. Nevertheless, ankylosing spondylitis (AC), which is regarded as a disease of the musculoskeletal apparatus, affecting mainly young men, remains one of the leading socioeconomic problems of our time, leading to disability in working age.