[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[Gastrointestinal tumors with SWI/SNF complex deficiency: a clinicopathological analysis of 36 cases].

Objective: To investigate the clinicopathological characteristics of gastrointestinal tumors with SWI/SNF complex deficiency and to perform a prognostic analysis of the patients. Methods: Gastrointestinal tumor cases with SWI/SNF complex deficiency expression diagnosed at the Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China from August 2021 to May 2023 were collected. Hematoxylin and eosin (HE) stained slides were reviewed, and immunohistochemical results were analyzed. Clinical and pathological information was recorded, and relevant literature was reviewed. Results: A total of 36 cases of gastrointestinal tumor with loss of SWI/SNF complex expression were identified, including 28 males (77.8%) and 8 females (22.2%). The average age at diagnosis was 70 years (range 48-85 years). Clinical staging showed 3 cases in stage Ⅰ (8.3%), 12 cases in stage Ⅱ (33.3%), 19 cases in stage Ⅲ (52.8%), and 2 cases in stage Ⅳ (5.6%). Complete or partial loss of ARID1A expression was observed in 20 cases (55.6%); complete or partial loss of SMARCA2 expression was observed in 24 cases (66.7%). SMARCA4 exhibited complete loss of expression in 4 cases (11.1%). Eleven cases (30.6%) showed concurrent complete or partial losses of both ARID1A and SMARCA2 expression. Twelve cases (33.3%) had mismatch repair protein deficiency, all of which were characterized by MLH1/PMS2 absence. Mismatch repair protein deficiency was associated with loss of ARID1A expression (P<0.01). Patients with mismatch repair protein deficiency were also associated with earlier clinical stage and a lower risk of lymph node metastasis compared to the ones with intact mismatch repair proteins (P<0.05). Conclusions: SWI/SNF complex deficiency in gastrointestinal tumors is associated with dedifferentiation and often accompanied by mismatch repair protein deficiency. Compared to the cases with intact mismatch repair proteins, the cases with defective mismatch repair protein have an earlier clinical stage and a lower risk of lymph node metastasis.

[Application of modified urethral separation method in artificial urethral sphincter implantation and its influence on intraoperative urethral pressure profilometry].

Objective: To explore the application of modified urethral separation method in artificial urethral sphincter (AUS) implantation in patients with stress urinary incontinence (SUI), and its influence on the results of urethral pressure profilometry. Methods: A prospective collection of clinical data was conducted on 25 patients with stress urinary incontinence who underwent modified urethral separation method in AUS implantation and underwent urethral pressure profilometry in Beijing Hospital, Beijing Jishuitan Hospital Affiliated to Capital Medical University and the Second Hospital Affiliated to Tianjin Medical University from March 2019 to June 2023. The improved urethral separation method was to borrow part of the white membrane tissue of the cavernous body while freeing the dorsal side of the cavernous body of the urethra. The circumference of the urethra, sleeve size, and urethral pressure were recorded, the patient's autonomous urinary control before and after surgery and the changes of the international consultation on incontinence questionnaire-short form (ICI-Q-SF) score, incontinence quality of life questionnaire (I-QoL) score, urinary frequency score, nocturia score were compared. Follow-up was conducted in the clinic or by telephone at 1, 3, 6, and 12 months after activation of the device, and once a year thereafter. Local skin status and urine control were assessed, residual urine volume was measured by ultrasound and subjective score scale was completed. Results: All patients were male, aged 27-85 (65.8±15.7) years old. The circumference of the cuff used in this study was 4.0 cm in 4 patients (16.0%), 4.5 cm in 16 patients (64.0%), 5.0 cm in 4 patients (16.0%), and 5.5 cm in 1 patient (4.0%). Among them, the urethral circumference matched the cuff size in 14 cases (56.0%), the urethral circumference was smaller than the cuff size in 4 cases (16.0%), and the urethral circumference was larger than the cuff size in 7 cases (28.0%). Preoperative urodynamic examination showed that the maximum urethral pressure (MUP) was (78.0±25.9) cmH2O, (1 cmH2O=0.098 kPa) and the maximum urethral closure pressure (MUCP) was (53.4±26.6) cmH2O. The MUP of AUS device in the inactivated state was (88.0±26.5) cmH2O, which was not significantly higher than that before operation (P>0.05). The MUCP was (68.2±24.5) cmH2O, which was significantly higher than that before operation (P<0.05). The MUP and MUCP of the AUS device in the activated state were (146.6±25.2) cmH2O and (123.0±28.3) cmH2O, which were significantly higher than those before surgery and in the inactivated state (both P<0.001). All patients in the group reached the social urinary control standards at the first month of device activation. During a follow-up period of 2-50 months, 22 patients (88.0%) used the initial AUS device and all met social urinary control standards. The AUS device was replaced in 1 case. One patient died of cerebrovascular accident. One patient removed the device due to complications. The number of pads [M (Q1, Q3)] used in 25 patients before and after operation was 4.5 (3.0, 6.5) and 1 (0, 1) respectively, with statistically significant differences (P<0.001). ICI-Q-SF score, I-QoL score, urinary frequency score and nocturia score of 25 patients were significantly improved after surgery (all P<0.05). The incidence of postoperative complications was 20.0% (5/25), including 2 cases of painless hematuria, 1 case of infection, 1 case of urethral erosion, and 1 case of dysuria. Except for one patient who experienced urethral erosion and had his sleeve removed, the remaining four patients regained social urination control with active support treatment, and no symptoms recurred until the last follow-up. Conclusion: The modified urethral separation method has no significant effect on urethral pressure in patients with SUI, and can increase the volume of peri-urethral tissue in the cuff, thereby reducing the risk of intraoperative urethral injury and the incidence of postoperative urethral erosion.

[Research progress in associations between dental caries and systemic diseases].

Dental caries is a bacteria-mediated, multifactorial, chronic progressive disease that results in the phasic demineralization and remineralization of dental hard tissues. In recent years, amounts of studies have focused on the association between dental caries and systemic diseases. This paper reviews the researches about associations between caries and systemic diseases. An electronic search was conducted in PubMed and Web of Science for articles published from 2003 to 2022 in the English language. Studies were included in the following ten categories of systemic diseases: cardiovascular diseases, metabolic disorders, respiratory diseases, autoimmune rheumatic diseases, neurologic diseases, gastrointestinal diseases, kidney diseases, skin diseases, iron deficiency anaemia and tumors. This review discusses the relationship between dental caries and systemic diseases, as well as the potentially involved mechanisms, providing new ideas for disease prevention, diagnosis, and treatment strategies for dentists and other clinicians.

Clinically Oriented CBCT Periapical Lesion Evaluation via 3D CNN Algorithm.

Apical periodontitis (AP) is one of the most prevalent disorders in dentistry. However, it can be underdiagnosed in asymptomatic patients. In addition, the perioperative evaluation of 3-dimensional (3D) lesion volume is of great clinical relevance, but the required slice-by-slice manual delineation method is time- and labor-intensive. Here, for quickly and accurately detecting and segmenting periapical lesions (PALs) associated with AP on cone beam computed tomography (CBCT) images, we proposed and geographically validated a novel 3D deep convolutional neural network algorithm, named PAL-Net. On the internal 5-fold cross-validation set, our PAL-Net achieved an area under the receiver operating characteristic curve (AUC) of 0.98. The algorithm also improved the diagnostic performance of dentists with varying levels of experience, as evidenced by their enhanced average AUC values (junior dentists: 0.89-0.94; senior dentists: 0.91-0.93), and significantly reduced the diagnostic time (junior dentists: 69.3 min faster; senior dentists: 32.4 min faster). Moreover, our PAL-Net achieved an average Dice similarity coefficient over 0.87 (0.85-0.88), which is superior or comparable to that of other existing state-of-the-art PAL segmentation algorithms. Furthermore, we validated the generalizability of the PAL-Net system using multiple external data sets from Central, East, and North China, showing that our PAL-Net has strong robustness. Our PAL-Net can help improve the diagnostic performance and speed of dentists working from CBCT images, provide clinically relevant volume information to dentists, and can potentially be applied in dental clinics, especially without expert-level dentists or radiologists.

Effects of phenylephrine on systemic and cerebral circulations in humans: a systematic review with mechanistic explanations.

We conducted a systematic review of the literature reporting phenylephrine-induced changes in blood pressure, cardiac output, cerebral blood flow and cerebral tissue oxygen saturation as measured by near-infrared spectroscopy in humans. We used the proportion change of the group mean values reported by the original studies in our analysis. Phenylephrine elevates blood pressure whilst concurrently inducing a reduction in cardiac output. Furthermore, despite increasing cerebral blood flow, it decreases cerebral tissue oxygen saturation. The extent of phenylephrine's influence on cardiac output (r = -0.54 and p = 0.09 in awake humans; r = -0.55 and p = 0.007 in anaesthetised humans), cerebral blood flow (r = 0.65 and p = 0.002 in awake humans; r = 0.80 and p = 0.003 in anaesthetised humans) and cerebral tissue oxygen saturation (r = -0.72 and p = 0.03 in awake humans; r = -0.24 and p = 0.48 in anaesthetised humans) appears closely linked to the magnitude of phenylephrine-induced blood pressure changes. When comparing the effects of phenylephrine in awake and anaesthetised humans, we found no evidence of a significant difference in cardiac output, cerebral blood flow or cerebral tissue oxygen saturation. There was also no evidence of a significant difference in effect on systemic and cerebral circulations whether phenylephrine was given by bolus or infusion. We explore the underlying mechanisms driving the phenylephrine-induced cardiac output reduction, cerebral blood flow increase and cerebral tissue oxygen saturation decrease. Individualised treatment approaches, close monitoring and consideration of potential risks and benefits remain vital to the safe and effective use of phenylephrine in acute care.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Preparation, thermal storage properties and application of sodium acetate trihydrate/expanded graphite composite phase change materials.

The development of energy storage technology is beneficial for the efficient use of energy and sustainable development. As an effectual approach for storing and transporting thermal energy, latent heat storage using phase change materials (PCMs) has attracted tremendous attention. However, low thermal conductivity, poor stability, and leakages are considerable challenges to the widespread application of solid-liquid PCMs. Composite phase change materials (CPCMs) were prepared by combining expanded graphite (EG) and sodium acetate trihydrate (CH3COONa·3H2O, SAT). EG as a supporting material plays a crucial part in both enhancing the thermal conductivity and preventing the melted PCMs from leakage. The chemical structure, micromorphology, thermal stability, thermal conductivity, phase change behavior and heat storage performance of SAT/EG CPCMs have been extensively investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermal conductivity analysis, differential scanning calorimetry (DSC), and cycling stability measurement. The results of SEM indicate that EG with a loose and porous layered structure has a good molding effect and can adsorb SAT well. XRD and FTIR results show that only a simple physical combination between EG and SAT exists, and no new substances have been produced. Compared with pure SAT, thermal conductivity and supercooling tests show that the supercooling degree of the CPCMs was decreased and the thermal conductivity was increased by 205.1%. In addition, the addition of 2 wt% of disodium hydrogen phosphate dodecahydrate (Na2HPO4·12H2O, DHPD) as a nucleating agent and 0.5 wt% of gelatin as a thickening agent to SAT could reduce the supercooling degree and inhibit the phase separation well. Based on SAT/EG-8% CPCMs, an oven with phase change energy storage was designed and the heat storage/release performance of the oven was investigated under different operating conditions.

[Clinical characteristics and therapeutic effectiveness of post craniotomy cervicogenic headache].

From January 2019 to December 2021, the clinical data of 151 patients with post craniotomy cervicogenic headache from Beijing Tiantan Hospital affiliated to Capital Medical University were retrospectively collected. The characteristics of cervicogenic headache were summarized, the numerical rating score (NRS) of patients before and after treatment of compound opioids and/or cervical nerve block was compared, and the occurrence of related adverse reactions and complications was counted. The onset of cervicogenic headache in 151 patients was on the (5.5±2.0) d after craniotomy, of which 131 (86.8%) had unilateral pain, pain in 127 (84.1%) could be induced by cervical activity, and 118 (78.1%) had limited neck movement. Of the 124 patients treated with compound capsule of oxycodone and acetaminophen, 85 (68.5%) patients had an NRS of (8.01±0.82) before treatment and 2.0 (1.0, 3.0) after treatment (P<0.001). Thirty-nine patients who did not respond to medical therapy received cervical nerve block, and the NRS scores before and after receiving the nerve block were (7.49±1.12) and 2.0 (1.0, 2.5), respectively, with a statistically significant difference (P<0.001). Twenty-seven patients who received cervical nerve block without medical treatment, and the NRS before and after treatment was (9.0±0.9) and 1.0 (1.0, 3.0), respectively, with a statistically significant difference (P<0.001). Among the 124 patients receiving medication, 14 (11.3%) developed mild dizziness and nausea, which were resolved after stopping the drug, and no other drug-related adverse reactions were found. None of the patients who received nerve blocks saw complications associated with nerve block procedures. Compound capsule of oxycodone and acetaminophen are effective for most of patients with post craniotomy cervicogenic headache. Cervical nerve block is effective and safe for patients with or without drug resistance.

[The efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy in children with allergic rhinitis during treatment].

Objective: To evaluate the efficacy and safety of standardized dust mite allergen subcutaneous immunotherapy (SCIT) in children with allergic rhinitis (AR) during treatment. Methods: A total of 283 children with AR diagnosed with definite dust mite allergy and completed 2 to 3 years of SCIT who attended the Department of Otorhinolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, from August 2019 to October 2021 were included, including 205 males and 78 females, with a mean age of 10.8 years. The total nasal symptoms score (TNSS), symptom medication score (SMS), rhinoconjunctivitis quality of life questionnaire (RQLQ) and visual analogue scale (VAS) before and after 2 to 3 years' treatment were recorded, and the differences before and after treatment were compared. Adverse reactions during SCIT were recorded to evaluate its safety. SPSS 22.0 software was used for statistical analysis. Results: The overall effectiveness rate during SCIT in 283 children with AR was 89.4% (253/283). Compared with baseline, all symptom scores, medication scores and quality of life scores were significantly lower after 2 to 3 years of SCIT (all P<0.05). Further group comparisons showed positive efficacy in patients with different clinical characteristics, including age, gender, smoking status, family history of AR, symptom severity, mono-or poly-allergy, and second immunization, with no statistically significant differences between groups (all P>0.05). A total of 12 735 injections were administered during the SCIT, and a total of 213 (1.67%) injections of local adverse reactions occurred, mainly in the initial treatment phase, and the diameter of the local air mass was mostly 5 to 20 mm; 71 (0.56%) injections of systemic adverse reactions occurred, mainly in the initial treatment phase, and most of them were grade 1 reactions with no serious systemic adverse reaction such as shock. Conclusion: Standardized dust mite SCIT has a good safety profile and definite efficacy in treating AR children with different clinical characteristics. It can significantly improve all symptoms, reduce the use of symptomatic drugs and improve their quality of life.

Purtscher-like retinopathy in systemic lupus erythematosus: clinical features, risk factors and prognosis.

BACKGROUND: Purtscher-like retinopathy (PLR) is a rare ocular manifestation in systemic lupus erythematosus (SLE) with poor prognosis, but its clear risk factors and treatment consensus are still lacking. AIM: To investigate the clinical features, risk factors and prognosis of PLR in SLE patients. DESIGN AND METHODS: A retrospective analysis was conducted on SLE patients with PLR admitted at Peking Union Medical College Hospital from 2013 to 2022. Clinical data, including demographic characteristics, lupus-related features, laboratory findings and ophthalmologic examinations, were collected and analyzed. The prognosis was evaluated based on best-corrected visual acuity and ophthalmologic outcomes. RESULTS: Seventeen SLE patients (32 eyes) diagnosed with PLR were included, along with a random selection of 100 SLE patients without retinopathy and 100 with retinal microvasculopathy as controls. Patients with PLR had a significantly younger age, a higher proportion of hemolytic anemia, a shorter duration of SLE, a higher SLE disease activity index-2000 (SLEDAI-2K) score, higher erythrocyte sedimentation rate (ESR) values and lower hemoglobin (HGB) values than the group without retinopathy (P < 0.05). They also had a significantly higher SLEDAI-2K score, higher ESR values and higher white blood cell values (P < 0.05) than the Microvasculopathy group. The majority of eyes (22/26, 84.62%) achieved stabilization at the last follow-up, with different therapeutic strategies, while a few (4/26, 15.38%) experienced complications or progression. CONCLUSION: This is the largest reported case series of PLR in SLE, which was associated with higher disease activity and poor visual prognosis. It was also associated with younger age, shorter SLE duration, concomitant hemolytic anemia, lower HGB and higher ESR value. Early recognition and prompt treatment are crucial for improving visual outcomes.

Feature pyramid network-based computer-aided detection and monitoring treatment response of brain metastases on contrast-enhanced MRI.

AIM: To investigate the value of feature pyramid network (FPN)-based computer-aided detection (CAD) of brain metastases (BMs) before and after non-surgical treatment, and to evaluate its performance in monitoring treatment response of BM on contrast-enhanced (CE) magnetic resonance imaging (MRI). MATERIAL AND METHODS: Eighty-five cancer patients newly diagnosed with BM who had undergone initial and follow-up three-dimensional (3D) CE MRI at Liaocheng People's Hospital were included retrospectively in this study. Manual detection (MD) was performed by reviewer 1. Computer-aided detection (CAD) was performed by reviewer 2 using uAI Discover-BMs software. The treatment response was assessed by the two reviewers for each patient separately. A paired chi-square test was used to compare the differences in the detection of BM between MD and CAD. Agreement between MD and CAD in monitoring treatment response was assessed by kappa test. RESULTS: The sensitivities of MD and CAD on initial 3D CE MRI were 78.65% and 99.13%, respectively. The sensitivities of MD and CAD on follow-up 3D CE MRI were 76.32% and 98.24%, respectively. There was a very good agreement between Reviewer 1 and Reviewer 2 in evaluating the treatment response of BM. CONCLUSION: FPN-based CAD has a higher sensitivity of close to 100% and lower false negatives (FNs) for BM detection, compared to MD. Although CAD had a few shortcomings in reflecting changes of BMs after treatment, it had high performance in monitoring treatment response of BM on CE MRI.

Achieving High Core Neuron Density in a Neuromorphic Chip Through Trade-off Among Area, Power Consumption, and Data Access Bandwidth.

As a crucial component of neuromorphic chips, on-chip memory usually occupies most of the on-chip resources and limits the improvement of neuron density. The alternative of using off-chip memory may result in additional power consumption or even a bottleneck for off-chip data access. This article proposes an on- and off-chip co-design approach and a figure of merit (FOM) to achieve a trade-off between chip area, power consumption, and data access bandwidth. By evaluating the FOM of each design scheme, the scheme with the highest FOM (1.085× better than the baseline) is adopted to design a neuromorphic chip. Deep multiplexing and weight-sharing technologies are used to reduce on-chip resource overhead and data access pressure. A hybrid memory design method is proposed to optimize on- and off-chip memory distribution, which reduces on-chip storage pressure and total power consumption by 92.88% and 27.86%, respectively, while avoiding the explosion of off-chip access bandwidth. The co-designed neuromorphic chip with ten cores fabricated under standard 55 nm CMOS technology has an area of 4.4 mm 2 and a core neuron density of 4.92 K/mm 2, an improvement of 3.39  âˆ¼ 30.56× compared with previous works. After deploying a full-connected and a convolution-based spiking neural network (SNN) for ECG signal recognition, the neuromorphic chip achieves 92% and 95% accuracy, respectively. This work provides a new path for developing high-density and large-scale neuromorphic chips.

Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.

Functional analysis of rare anti-Müllerian hormone protein-altering variants identified in women with PCOS.

Recently, rare heterozygous AMH protein-altering variants were identified in women with polycystic ovary syndrome (PCOS), causing reduced anti-Müllerian hormone (AMH) signaling. However, the exact functional mechanism remains unknown. Here, we analyzed the processing, secretion, and signaling of these AMH variants. Functional analysis of six PCOS-specific AMH variants (V12G, P151S, P270S, P352S, P362S, H506Q) and one control-specific variant (A519V) was performed in the mouse granulosa cell-line KK-1. Human (h) AMH-151S and hAMH-506Q have ∼90% decreased AMH signaling compared to wild-type (wt) AMH signaling. Coexpression of hAMH-151S or hAMH-506Q with wt-hAMH dose-dependently inhibited wt-hAMH signaling. Western blotting revealed that hAMH-151S and hAMH-506Q proteins were detected in the cell lysate but not in the supernatant. Confocal microscopy showed that HEK293 cells expressing hAMH-151S and hAMH-506Q had higher cellular AMH protein levels with endoplasmic reticulum (ER) retention compared to cells expressing wt-hAMH. Using two AMH ELISA kits, hAMH-151S was detected in the cell lysate, while only very low levels were detected in the supernatant. Both hAMH-362S and hAMH-519V were detectable using the automated AMH ELISA but showed severely reduced immunoactivity in the manual ELISA. Surprisingly, hAMH-506Q was undetectable in both the cell lysate and supernatant using either ELISA. However, in PCOS cases, heterozygous carriers of the P151S and H506Q variants still had detectable AMH in both assays. Thus, P151S and H506Q disrupt normal processing and secretion of AMH, causing ER retention. Additionally, AMH variants can impair the AMH immunoactivity. An AMH variant may be considered when serum AMH levels are relatively low in PCOS cases.

[Comparison of three methods for establishing rat peri-implantitis model].

OBJECTIVE: To compare the efficiency and effect of establishing rat peri-implantitis model by traditional cotton thread ligation and local injection of Porphyromonas gingivalis lipopolysaccharide (LPS) around the implant, as well as the combination of the two methods. METHODS: Left side maxillary first molars of 39 male SD rats were extracted, and titanium implants were implanted after four weeks of healing. After 4 weeks of implant osseointegration, 39 rats were randomly divided into 4 groups. Cotton thread ligation (n=12), local injection of LPS around the implant (n=12), and the two methods combined (n=12) were used to induce peri-implantitis, the rest 3 rats were untreated as control group. All procedures were conducted under 5% isoflurane inhalation anesthesia. The rats were sacrificed 2 weeks and 4 weeks after induction through carbon dioxide asphyxiation method. The maxilla of the rats in the test groups were collected and marginal bone loss was observed by micro-CT. The gingival tissues around the implants were collected for further real time quantitative PCR (RT-qPCR) analysis, specifically the expression of tumor necrosis factor-alpha (TNF-α) as well as interleukin-1ß (IL-1ß). The probing depth (PD), bleeding on probing (BOP) and gingival index (GI) of each rat in the experimental group were recorded before induction of inflammation and before death. RESULTS: After 4 weeks of implantation, the osseointegration of implants were confirmed. All the three test groups showed red and swollen gums, obvious marginal bone loss around implants. After 2 weeks and 4 weeks of inflammation induction, PD, GI and BOP of the three test groups increased compared with those before induction, but only BOP was statistically significant among the three test groups (P < 0.05). At the end of 2 weeks of inflammation induction, marginal bone loss was observed at each site in the cotton thread ligation group and the combined group. At each site, the bone resorption in the combined group was greater than that in the cotton thread ligation group, but the difference was not statistically significant (P > 0.05), bone resorption was observed at some sites of some implants in LPS local injection group. At the end of 4 weeks of inflammation induction, marginal bone loss was observed at all sites in each group. The marginal bone loss in the cotton thread ligation group and the combined group was greater than that in the LPS local injection group, and the difference was statistically significant (P < 0.05). At the end of 2 weeks and 4 weeks of induction, the expression of TNF-α and IL-1ß in the test groups were higher than those in the control group (P < 0.05). CONCLUSION: Compared with local injection of LPS around the implant, cotton thread ligature and the two methods combined can induce peri-implantitis in rats better and faster.

Study of pharyngeal airway morphology with CBCT: Benefits of four premolar extraction orthodontic treatments.

Background and Aim: Four premolars extractions are routine procedures for correction of malocclusion, but will inevitably lead to a reduction of tongue space, whether this will weaken the pharyngeal airway remains a controversy. Patients and Methods: Cone-beam computed tomography (CBCT) radiographs of 80 patients who completed four premolar extraction orthodontic treatments were collected and divided into three anteroposterior skeletal groups according to the ANB (angle subspinale to nasion to supramentale) value. Linear, angular, cross-sectional area, and volumetric dimensions of the pharyngeal airway were measured using Dolphin Imaging 11.9 software. One-way analysis of variance and Pearson's correlation coefficient test were performed to assess the intergroup comparisons. Treatment changes were evaluated with two-sample t-tests. Results: In intergroup comparisons, vertical linear and cross-sectional area differences were identified in S-Go/N-Me, VD1, VD1/N-Me, VD2/N-Me, AA, OAA and OMINI (p<0.05), while other measurements showed no significant differences. Angle2, the tilting degree of the pharyngeal airway, showed a positive correlation with ANB (p<0.05). As for the treatment changes, a significant increase was found in the pharyngeal airway in the Class I group (OUA p<0.05, VD1 p<0.001, VD2 p<0.05) and Class II group (VD1 p<0.001. VD2, p<0.05), and inversely, a significant decrease was found in the pharyngeal airway in the Class III group (OAA p<0.05, OMINI p<0.05, OUA p<0.05). No volumetric difference was identified. Interestingly, regarding the preoperative pharyngeal airway size, values trended to the mean value significantly. Conclusion: Four premolar extraction orthodontic treatments did not affect the pharyngeal airway volume except for the vertical liner and cross-sectional area dimensions. The trend of the gold standard suggested a positive influence of four premolar extraction orthodontic treatments.