Network pharmacology-based strategy to investigate the mechanisms of artemisinin in treating primary Sjögren's syndrome.

OBJECTIVE: The study aimed to explore the mechanism of artemisinin in treating primary Sjögren's syndrome (pSS) based on network pharmacology and experimental validation. METHODS: Relevant targets of the artemisinin and pSS-related targets were integrated by public databases online. An artemisinin-pSS network was constructed by Cytoscape. The genes of artemisinin regulating pSS were imported into STRING database to construct a protein-protein interaction (PPI) network in order to predict the key targets. The enrichment analyses were performed to predict the crucial mechanism and pathway of artemisinin against pSS. The active component of artemisinin underwent molecular docking with the key proteins. Artemisinin was administered intragastrically to SS-like NOD/Ltj mice to validate the efficacy and critical mechanisms. RESULTS: Network Pharmacology analysis revealed that artemisinin corresponded to 412 targets, and pSS related to 1495 genes. There were 40 intersection genes between artemisinin and pSS. KEGG indicated that therapeutic effects of artemisinin on pSS involves IL-17 signaling pathway, HIF-1 signaling pathway, apoptosis signaling pathway, Th17 cell differentiation, PI3K-Akt signaling pathway, and MAPK signaling pathway. Molecular docking results further showed that the artemisinin molecule had higher binding energy by combining with the key nodes in IL-17 signaling pathway. In vivo experiments suggested artemisinin can restored salivary gland secretory function and improve the level of glandular damage of NOD/Ltj mice. It contributed to the increase of regulatory T cells (Tregs) and the downregulated secretion of IL-17 in NOD/Ltj model. CONCLUSION: The treatment of pSS with artemisinin is closely related to modulating the balance of Tregs and Th17 cells via T cell differentiation.

Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders: A case report and review of literature.

BACKGROUND: The relation between orthodontic treatment and temporomandibular disorders (TMDs) is under debate; the management of TMD during orthodontic treatment has always been a challenge. If TMD symptoms occur during orthodontic treatment, an immediate pause of orthodontic adjustments is recommended; the treatment can resume when the symptoms are managed and stabilized. CASE SUMMARY: This case report presents a patient (26-year-old, female) with angle class I, skeletal class II and TMDs. The treatment was a hybrid of clear aligners, fixed appliances and temporary anchorage devices (TADs). After 3 mo resting and treatment on her TMD, the patient's TMD symptom alleviated, but her anterior occlusion displayed deep overbite. Therefore, the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves. After the levelling, the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion. After careful examination of temporomandibular joints (TMJ) position, the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion. Eventually, the improved facial appearance and relatively stable occlusion were achieved. The 1-year follow-up records showed there was no obvious change in TMJ morphology, and her occlusion was stable. CONCLUSION: TMD screening and monitoring is of great clinical importance in the TMD susceptible patients. Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth (p <0.001), dry eyes (p <0.001), fatigue (p <0.001), arthralgia (p <0.001), and dental caries (p <0.001) and higher rates of anti-Sjögren syndrome A (p < 0.05), anti-Ro52 (p < 0.05), and anti-SSB (p < 0.05) positivity than their control groups, with prevalence increasing with disease duration (ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Treatment of severe open bite and mandibular condyle anterior displacement by mini-screws and four second molars extraction: A case report.

BACKGROUND: Temporomandibular joint (TMJ) disorders are closely related to high-angle and skeletal Class II malocclusion. Sometimes pathological changes in the mandibular condyle can cause open bite to occur after growth is complete. CASE SUMMARY: This article is about the treatment of an adult male patient with a severe hyperdivergent skeletal Class II base, an unusual and gradually occurring open bite and an abnormal mandibular condyle anterior displacement. Because the patient refused surgery, four second molars with cavities and root canal therapy were extracted, and four mini-screws were used for intrusion of the posterior teeth. The treatment duration was 22 mo, and after the treatment, the open bite was corrected and the displaced mandibular condyles were seated back to the articular fossa as shown by cone-beam computed tomography (CBCT). Based on the patient's open bite history, the result of clinical examinations and CBCT comparisons, we believe it is possible that the occlusion interference was eliminated after the four second molars were extracted and the posterior teeth were intruded, and the patient's condyle spontaneously returned to its physiologic position. Finally, a normal overbite was established, and stable occlusion was achieved. CONCLUSION: This case report suggested that identifying the cause of open bite is essential, and the TMJ factors for hyperdivergent skeletal Class II cases should be particularly examined. For these cases, intruding posterior teeth may place the condyle in a more appropriate position and provide an environment suitable for TMJ recovery.

Sex Difference in Primary Sjögren Syndrome: A Medical Records Review Study.

OBJECTIVES: The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS. METHODS: Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ 2 test. RESULTS: This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries ( p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels ( p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 ( p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity ( p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease ( p < 0.05). CONCLUSIONS: Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital.

Knowledge mapping of biological disease-modifying anti-rheumatic drugs for axial spondyloarthritis: a bibliometric study.

Various biological disease-modifying anti-rheumatic drugs (bDMARDs) have been applied for treating axial spondyloarthritis (axSpA). However, there is a glaring absence of a bibliometric analysis on bDMARDs against axSpA. Articles related to use of bDMARDs in treating axSpA published from 2004 to 2022 were searched from the Web of Science Core Collection. VOS viewer 1.6.18 and CiteSpace 6.1.R2 were used to analyze and visualize the quantity and citations of publications, as well as to identify "research hotspots" and trends in this field. BibExcel version 1.0.0 and gCLUTO version 1.0 were used to build matrices for bi-clustering analysis. A total of 2546 articles referring to bDMARDs for treatment of axSpA were included in this bibliometric analysis. Overall, the number of publications has been increasing steadily annually. The USA (23.21%, 591 publications) ranked first with the largest output of papers, followed by Germany, and the Netherlands. Rheumazentrum Ruhrgebiet ranked first as the most frequent publisher (119 articles). Annals of the Rheumatic Diseases published the most documents (6.76%, 172 publications) in this field. The predominant hotspots have been "tuberculosis," "IL-17," and "quality of life" in the field until 2020. Since 2015, "biosimilar pharmaceuticals" has retained the popularity. Current research hotspots are "spinal radiographic progression," Janus kinase (JAK) inhibitors, and adverse events (AEs). Machine learning has become popular gradually. Globally, there has been a steady increase in the number of studies on bDMARDs use against axSpA. JAK inhibitors, spinal radiographic progression, biosimilar pharmaceuticals, and AEs are current research hotspots. Machine learning is emerging research hotspots and trends in this field.

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma.

The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1-associating protein)-mediated TEAD4 m6A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

Orthodontic-surgical treatment of an Angle Class II malocclusion patient with mandibular hypoplasia and missing maxillary first molars: A case report.

BACKGROUND: Adult patients presenting with Angle Class II division 1 malocclusions that have a strong skeletal etiology can be challenging for clinicians, particularly if accompanied by retrognathia of the mandible and a dolichofacial growth pattern. CASE SUMMARY: In this case report, we describe the successful orthodontic and surgical management of a 20-year-old woman with an Angle Class II malocclusion with a severe anteroposterior skeletal discrepancy characterized by mandibular deficiency. She had incompetent lips, dental and skeletal Class II malocclusion, high mandibular plane angle, mild mandibular crowding, and two missing maxillary first molars. The treatment plan comprised: (1) Extraction of two mandibular second premolars to decompensate and retract mandibular incisors; (2) pre-surgical alignment, leveling, and space closure of the teeth in both arches, and protraction of the second maxillary molars to close the maxillary space; (3) surgical treatment including a LeFort I osteotomy for maxillary retraction and rotation, a bilateral sagittal split osteotomy for mandibular advancement and rotation, and a genioplasty for correctting the skeletal deformities; and (4) post-surgical correction of the malocclusion. CONCLUSION: The patient's facial esthetics was significantly improved and a desirable occlusion was achieved after 16 mo treatment. Follow-up records after 2 years showed stable esthetics and function.

Distinct clinical phenotypes of primary Sjögren's syndrome differ by onset age: a retrospective study of 742 cases and review of the literature.

OBJECTIVES: To study the clinical characteristics of primary Sjögren's syndrome (pSS) with different onset age, and perform a review of the literature to confirm if the clinical phenotypes are affected by onset age in patients with pSS. METHODS: Data of 742 patients with pSS were retrospectively analysed. Patients were divided into three groups according to onset age: young-onset pSS (YopSS, <35 years), adult-onset pSS (AopSS, ≥35 and ≤65 years), and elderly-onset pSS (EopSS, >65 years). Clinical characteristics were compared among three groups and further multiple comparisons were conducted by Bonferroni adjustment. The Chi-squared test for linear-by-linear association was used to explore variation tendency. RESULTS: This study included 105 (14.2%), 533 (71.8%), and 104 (14.0%) cases of YopSS, AopSS, and EopSS, respectively. YopSS demonstrated lower prevalence of dry mouth, abnormal Schirmer I tests, and interstitial lung disease (ILD), but higher proportions of low C3 and C4 levels, and ANA, anti-SSA, anti-SSB, and rheumatoid factor (RF) positivity than AopSS and EopSS. The proportions of dry mouth (p=0.004), abnormal Schirmer I tests (p=0.002), and ILD (p<0.001) tended to increase with the increase of onset age, while the prevalence of leukopenia (p=0.011), low C3 (p=0.001), low C4 (p=0.001), and ANA (p<0.001), anti-SSA (p<0.001), anti-SSB (p<0.001) and RF (p<0.001) positivity tended to decrease with an increase in onset age. CONCLUSIONS: YopSS demonstrated less dryness and ILD, but more immunologic disorders. ILD prevalence were directly proportional to onset age of pSS; however, leukopenia, hypocomplementaemia, and autoantibody positivity showed opposite trends.

Retrorectal mucinous adenocarcinoma arising from a tailgut cyst: A case report and review of literature.

BACKGROUND: Tailgut cysts are defined as congenital cysts that develop in the rectosacral space from the residue of the primitive tail. As a congenital disease, caudal cysts are very rare, and their canceration is even rarer, which makes the disease prone to misdiagnosis and delayed treatment. We describe a case of caudal cyst with adenocarcinogenesis and summarize in detail the characteristics of cases with analytical value reported since 1990. CASE SUMMARY: A 35-year-old woman found a mass in her lower abdomen 2 mo ago. She was asymptomatic at that time and was not treated because of the coronavirus disease 2019 pandemic. Two weeks ago, the patient developed abdominal distension and right waist discomfort and came to our hospital. Except for the high level of serum carcinoembryonic antigen, the medical history and laboratory tests were not remarkable. Magnetic resonance imaging showed a well-defined, slightly lobulated cystic-solid mass with a straight diameter of approximately 10 cm × 9 cm in the presacral space, slightly high signal intensity on T2-weighted imaging, and moderate signal intensity on T1-weighted imaging. The mass was completely removed by laparoscopic surgery. Histopathological examination showed that the lesion was an intestinal mucinous adenocarcinoma, and the multidisciplinary team decided to implement postoperative chemotherapy. The patient recovered well, the tumor marker levels returned to normal, and tumor-free survival has been achieved thus far. CONCLUSION: The case and literature summary can help clinicians and researchers develop appropriate examination and therapeutic methods for diagnosis and treatment of this rare disease.

Factors associated with secondary immune thrombocytopenia in patients with primary Sjögren's syndrome: a retrospective study of 639 cases.

OBJECTIVES: To investigate the clinical characteristics and relevant factors of secondary immune thrombocytopenia (ITP) in patients with primary Sjögren's syndrome (pSS). METHODS: Patients with pSS being treated between 2013 and 2020 in China-Japan Friendship Hospital were retrospectively analysed. Clinical characteristics were compared between pSS patients with and without secondary ITP. Logistic regression analysis was performed to identify factors associated with secondary ITP in patients with pSS. RESULTS: 639 patients with pSS were included in this study, among which 566 (88.6%) were women. The prevalence of secondary ITP in patients with pSS were 12.4%. Among pSS patients with secondary ITP, 55.7% had mucocutaneous bleeding and 8.9% experienced visceral bleeding. Lymphopenia (OR=3.154, 95% CI 1.185-8.395, p=0.021), anaemia (OR=2.416, 95% CI 1.250-4.668, p=0.009), low C4 (OR=2.904, 95% CI 1.563-5.394, p=0.001), and positive anti-RNP (OR=2.777, 95% CI 1.070-7.202, p=0.036) were significantly related to secondary ITP, while interstitial lung disease (ILD, OR=0.429, 95% CI 0.203-0.907, p=0.027), ANA ≥1:320 (OR=0.469, 95% CI 0.221-0.996, p=0.049) and positive anti-SSB (OR=0.288, 95% CI 0.126-0.685, p=0.003) were negatively associated with secondary ITP in patients with pSS. CONCLUSIONS: Over 10% of patients with pSS had secondary ITP, among whom visceral bleeding was comparatively rare. Lymphopenia and anaemia were positively related to secondary ITP, while ILD was negatively associated with secondary ITP. Low C4 and positive anti-RNP seem to be two potential risk factors for secondary ITP in patients with pSS, while ANA ≥1:320 and positive anti-SSB may be two potential protective factors.

Therapeutic effect of oxyberberine on obese non-alcoholic fatty liver disease rats.

BACKGROUND: Berberine (BBR) has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The metabolites of BBR were believed to contribute significantly to its pharmacological effects. Oxyberberine (OBB), a gut microbiota-mediated oxidative metabolite of BBR, has been firstly identified in our recent work. PURPOSE: Here, we aimed to comparatively investigate the anti-NAFLD properties of OBB and BBR. METHODS: The anti-NAFLD effect was evaluated in high-fat diet-induced obese NAFLD rats with biochemical/ELISA tests and histological staining. The related gene and protein expressions were detected by qRT-PCR and Western blotting respectively. Molecular docking and dynamic simulation were also performed to provide further insight. RESULTS: Results indicated OBB remarkably and dose-dependently attenuated the clinical manifestations of NAFLD, which (100 mg/kg) achieved similar therapeutic effect to metformin (300 mg/kg) and was superior to BBR of the same dose. OBB significantly inhibited aberrant phosphorylation of IRS-1 and up-regulated the downstream protein expression and phosphorylation (PI3K, p-Akt/Akt and p-GSK-3ß/GSK-3ß) to improve hepatic insulin signal transduction. Meanwhile, OBB treatment remarkably alleviated inflammation via down-regulating the mRNA expression of MCP-1, Cd68, Nos2, Cd11c, while enhancing Arg1 mRNA expression in white adipose tissue. Moreover, OBB exhibited closer affinity with AMPK in silicon and superior hyperphosphorylation of AMPK in vivo, leading to increased ACC mRNA expression in liver and UCP-1 protein expression in adipose tissue. CONCLUSION: Taken together, compared with BBR, OBB was more capable of maintaining lipid homeostasis between liver and WAT via attenuating hepatic insulin pathway and adipocyte inflammation, which was associated with its property of superior AMPK activator.

Berberine impairs embryonic development in vitro and in vivo through oxidative stress-mediated apoptotic processes.

Berberine, an isoquinoline alkaloid isolated from several traditional Chinese herbal medicines, has been shown to suppress growth and induce apoptosis in some tumor cell lines. However, berberine has also been reported to attenuate H2 O2 -induced oxidative injury and apoptosis. The basis for these ambiguous effects of berberine-triggering or preventing apoptosis-has not been well characterized to date. In the current investigation, we examined whether berberine exerts cytotoxic effects on mouse embryos at the blastocyst stage and affects subsequent embryonic development in vitro and in vivo. Treatment of blastocysts with berberine (2.5-10 µM) induced a significant increase in apoptosis and a corresponding decrease in trophectoderm cell number. Moreover, the implantation success rate of blastocysts pretreated with berberine was lower than that of their control counterparts. Pretreatment with berberine was also associated with increased resorption of postimplantation embryos and decreased fetal weight. In an animal model, intravenous injection of berberine (2, 4, or 6 mg/kg body weight/d) for 4 days resulted in apoptosis of blastocyst cells and early embryonic developmental injury. Berberine-induced injury of mouse blastocysts appeared to be attributable to oxidative stress-triggered intrinsic apoptotic signaling processes that impaired preimplantation and postimplantation embryonic development. Taken together, our results clearly demonstrate that berberine induces apoptosis and retards early preimplantation and postimplantation development of mouse embryos, both in vitro and in vivo.

Direct characterization of motion-dependent parameters of sperm in a microfluidic device: proof of principle.

BACKGROUND: Semen analysis is essential for evaluating male infertility. Besides sperm concentration, other properties, such as motility and morphology, are critical indicators in assessing sperm quality. Nevertheless, rapid and complete assessment of these measures still presents considerable difficulty and involves a range of complex issues. Here we present a microfluidic device capable of quantifying a range of properties of human sperm via the resistive pulse technique (RPT). METHODS: An aperture, designed as a long channel, was used to allow the quantification of various properties as sperm swam through. RESULTS: The time trace of the voltage drop across the aperture during sperm passage contained a wealth of information: the sperm volume was presented by the amplitude of the induced pulse, the swim velocity was evaluated via the duration, and the beat frequency was calculated from the voltage undulation superposed on the pulse signal. The RPT measurement of swim velocity and beat frequency showed a correlation with the same observation in a microscope (R(2) = 0.94 and 0.70, respectively). CONCLUSIONS: The proposed proof of principle enables substantial quantification of the motion-dependent properties of sperm. Because this approach requires only a current/voltage source and data analysis, it is economically advantageous compared with optical methods for characterizing sperm motion. Furthermore, this approach may be used to characterize sperm morphology.