Adipocyte enhancer binding protein 1 knockdown alleviates osteoarthritis through inhibiting NF-κB signaling pathway-mediated inflammation and extracellular matrix degradation.

Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients (n = 20) compared to their normal controls (n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1ß treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1ß-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.

Construction and validation of a nomogram prediction model for the progression to septic shock in elderly patients with urosepsis.

Background: Septic shock is a clinical syndrome characterized by the progression of sepsis to a severe stage. Elderly patients with urosepsis in the intensive care unit (ICU) are more likely to progress to septic shock. This study aimed to establish and validate a nomogram model for predicting the risk of progression to septic shock in elderly patients with urosepsis. Methods: We extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV dataset was split into a training set for model development and an internal validation set to assess model performance. Further external validation was performed using a distinct dataset sourced from the eICU-CRD. Predictors were screened using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses. The evaluation of model performance included discrimination, calibration, and clinical usefulness. Results: The study demonstrated that the Glasgow Coma Scale (GCS), white blood count (WBC), platelet, blood urea nitrogen (BUN), calcium, albumin, congestive heart failure (CHF), and invasive ventilation were closely associated with septic shock in the training cohort. Nomogram prediction, utilizing eight parameters, demonstrated strong predictive accuracy with area under the curve (AUC) values of 0.809 (95 % CI 0.786-0.834), 0.794 (95 % CI 0.756-0.831), and 0.723 (95 % CI 0.647-0.801) in the training, internal validation, and external validation sets, respectively. Additionally, the nomogram demonstrated a promising calibration performance and significant clinical usefulness in both the training and validation sets. Conclusion: The constructed nomogram is a reliable and practical tool for predicting the risk of progression to septic shock in elderly patients with urosepsis. Its implementation in clinical practice may enhance the early identification of high-risk patients, facilitate timely and targeted interventions to mitigate the risk of septic shock, and improve patient outcomes.

Ordered planar plating/stripping enables deep cycling zinc metal batteries.

Metal anodes are emerging as culminating solutions for the development of energy-dense batteries in either aprotic, aqueous, or solid battery configurations. However, unlike traditional intercalation electrodes, the low utilization of "hostless" metal anodes due to the intrinsically disordered plating/stripping impedes their practical applications. Herein, we report ordered planar plating/stripping in a bulk zinc (Zn) anode to achieve an extremely high depth of discharge exceeding 90% with negligible thickness fluctuation and long-term stable cycling. The Zn can be plated/stripped with (0001)Zn preferential orientation throughout the consecutive charge/discharge process, assisted by a self-assembled supramolecular bilayer at the Zn anode-electrolyte interface. Through real-time tracking of the Zn atoms migration, we reveal that the ordered planar plating/stripping is driven by the construction of in-plane Zn─N bindings and the gradient energy landscape at the reaction fronts. The breakthrough results provide alternative insights into the ordered plating/stripping of metal anodes toward rechargeable energy-dense batteries.

Improved efficiency and stability using a novel elemental sulfur-based moving-bed denitrification process.

Elemental sulfur-based denitrification (ESDeN) technology is known as a cost-saving alternative to its heterotrophic counterpart for nutrient removal from organic-deficient water. However, the traditional fixed-bed reactor (FixBR), as an extensively used process, suffers from a low denitrification rate and even performance deterioration during long-term operation. Herein, we proposed a novel elemental sulfur-based denitrifying moving-bed reactor (ESDeN-MovBR), in which a screw rotator was employed to drive the filled sulfur particles to be microfluidized vertically (a state of vertical-loop movement). Our results showed that the ESDeN-MovBR realized much superior and more stable denitrification performance compared to the ESDeN-FixBR, as indicated by 3.09-fold higher denitrification rate and over one order of magnitude lower intermediates (NO2- and N2O) yield, which could last for over 100 days. Further research revealed that the microfluidization of sulfur particles facilitated the expelling of nitrogen bubbles and excessive biomass, resulting in the prolongation of actual hydraulic retention time by over 80 % and could partially explain the higher denitrification rate in ESDeN-MovBR. The remaining contribution to the improvement of denitrification rate was suggested to be result from changes in biofilm properties, in which the biofilm thickness of ESDeN-MovBR was found to be 3.29 times thinner yet enriched with 2.52 times more autotrophic denitrifiers. This study offered a completely new solution to boost up the denitrification performance of ESDeN technology and provided in-depth evidence for the necessity of biofilm thickness control in such technology.

Research progress of the effects of bisphenol analogues on the intestine and its underlying mechanisms: A review.

Bisphenol A (BPA) and its analogues have prompted rising concerns, especially in terms of human safety, due to its broad use and ubiquity throughout the ecosystem. Numerous studies reported various adverse effects of bisphenols, including developmental disorders, reproductive toxicity, cardiovascular toxicity, and so on. There is increasing evidence that bisphenols can enter the gastrointestinal tract. Consequently, it is important to investigate their effects on the intestine. Several in vivo and in vitro studies have examined the impacts of bisphenols on the intestine. Here, we summarized the literature concerning intestinal toxicity of bisphenols over the past decade and presented compelling evidence of the link between bisphenol exposure and intestinal disorders. Experiment studies revealed that even at low levels, bisphenols could promote intestinal barrier dysregulation, disrupt the composition and diversity of intestinal microbiota as well as induce an immunological response. Moreover, possible underlying mechanisms of these effects were discussed. Because of a lack of empirical data, the potential risk of bisphenol exposure in humans is still unidentified, particularly regarding intestinal disorders. Thus, we propose to conduct additional epidemiological investigations and animal experiments to elucidate the associations between bisphenol exposure and human intestinal health and reveal underlying mechanisms to develop preventative and therapeutic techniques.

Ultrasound-guided percutaneous micro-drainage tube irrigation combined with high negative pressure tube drainage versus debridement with closed suction irrigation for treating deep surgical site infection after spinal surgery.

It is difficult to avoid deep surgical site infection after spinal surgery. Debridement combined with closed suction irrigation (CSI) and other treatment methods lead to greater trauma and lower satisfaction. We developed a new method for the treatment of SSI, which has the advantages of less invasiveness and lower cost. The cohort of this retrospective study comprised 26 patients with SSI after undergoing spinal surgery in our hospital from August 2017 to March 2022. The patients were divided into CSI and microtube drainage group according to treatment methods. The durations of antibiotic use and hospital stay, hospitalization costs, and functional scores during follow-up were compared between the two groups. The only baseline characteristic that differed between the two groups was sex. Infection was controlled in both groups and there were no recurrences during follow-up. However, the length of hospital stay after the first operation and the total length of stay were significantly greater in the CSI group. Hospitalization costs and antibiotic costs were significantly higher in the CSI group. Additionally, the duration of intravenous antibiotic use was significantly longer in the CSI group. Both the CSI and microtube drainage groups had significantly improved of Short Form Health Survey (SF-36) scores 6 months postoperatively. However, 3 months postoperatively, SF-36 scores were significantly lower in the CSI group. Compared with debridement followed by CSI, percutaneous micro-drainage tube irrigation combined with high negative pressure tube drainage is a more efficient and economical means of treating SSI after spinal surgery.

Synergistic "Anchor-Capture" Enabled by Amino and Carboxyl for Constructing Robust Interface of Zn Anode.

While the rechargeable aqueous zinc-ion batteries (AZIBs) have been recognized as one of the most viable batteries for scale-up application, the instability on Zn anode-electrolyte interface bottleneck the further development dramatically. Herein, we utilize the amino acid glycine (Gly) as an electrolyte additive to stabilize the Zn anode-electrolyte interface. The unique interfacial chemistry is facilitated by the synergistic "anchor-capture" effect of polar groups in Gly molecule, manifested by simultaneously coupling the amino to anchor on the surface of Zn anode and the carboxyl to capture Zn2+ in the local region. As such, this robust anode-electrolyte interface inhibits the disordered migration of Zn2+, and effectively suppresses both side reactions and dendrite growth. The reversibility of Zn anode achieves a significant improvement with an average Coulombic efficiency of 99.22% at 1 mA cm-2 and 0.5 mAh cm-2 over 500 cycles. Even at a high Zn utilization rate (depth of discharge, DODZn) of 68%, a steady cycle life up to 200 h is obtained for ultrathin Zn foils (20 µm). The superior rate capability and long-term cycle stability of Zn-MnO2 full cells further prove the effectiveness of Gly in stabilizing Zn anode. This work sheds light on additive designing from the specific roles of polar groups for AZIBs.

Clinical Outcomes of Percutaneous Endoscopic Interlaminar Discectomy Using a Laminotomy Technique With Modified Stepwise Local Anesthesia.

BACKGROUND: Percutaneous endoscopic interlaminar discectomy (PEID) has been widely used in minimally invasive treatment of lumbar disc herniation (LDH) but is difficult to perform because of the narrow interlaminar window and painful for the patient. Therefore, further research is needed to find a safe and effective method to facilitate the development of PEID. METHODS: Seventy-one consecutive patients with LDH who underwent PEID using a laminotomy technique with modified stepwise local anesthesia between July 2017 and June 2020. All patients were followed up for at least 6 months. Preoperative patient demographics, perioperative outcomes, and clinical outcomes were recorded. Visual Analog Scale (VAS) scores, Oswestry Disability Index (ODI) scores, and Macnab criteria were used to assess clinical results. RESULTS: All patients underwent successful surgery under local anesthesia with no conversions to open surgery. The mean operation time was 79.56 ± 32.78 minutes and the average hospital stay was 6.44 ± 2.98 nights. Before surgery, the mean VAS score was 5.66 ± 1.206 and the mean ODI score was 68.41 ± 6.634; the respective scores were decreased to 0.65 ± 0.635 and 7.06 ± 1.594 after 4 weeks of follow-up (P < 0.001) and to 0.56 ± 0.691 and 7.11 ± 0.176 after 6 months (P < 0.001). According to the MacNab criteria, the outcome was excellent in 60 cases and good in the remaining 11 cases. CONCLUSIONS: PEID via a laminotomy technique with stepwise local anesthesia is safe and effective for L4-5 and L5-S1 LDH.

SDH mutations, as potential predictor of chemotherapy prognosis in small cell lung cancer patients.

PURPOSE: Small cell lung cancer (SCLC) is an aggressive and rapidly progressive malignant tumor characterized by a poor prognosis. Chemotherapy remains the primary treatment in clinical practice; however, reliable biomarkers for predicting chemotherapy outcomes are scarce. METHODS: In this study, 78 SCLC patients were stratified into "good" or "poor" prognosis cohorts based on their overall survival (OS) following surgery and chemotherapeutic treatment. Next-generation sequencing was employed to analyze the mutation status of 315 tumorigenesis-associated genes in tumor tissues obtained from the patients. The random forest (RF) method, validated by the support vector machine (SVM), was utilized to identify single nucleotide mutations (SNVs) with predictive power. To verify the prognosis effect of SNVs, samples from the cbioportal database were utilized. RESULTS: The SVM and RF methods confirmed that 20 genes positively contributed to prognosis prediction, displaying an area under the validation curve with a value of 0.89. In the corresponding OS analysis, all patients with SDH, STAT3 and PDCD1LG2 mutations were in the poor prognosis cohort (15/15, 100%). Analysis of public databases further confirms that SDH mutations are significantly associated with worse OS. CONCLUSION: Our results provide a potential stratification of chemotherapy prognosis in SCLC patients, and have certain guiding significance for subsequent precise targeted therapy.

Risk factors for incisional complications after lumbar internal fixation via posterior midline approach: A case-control study of 455 consecutive cases.

To analyse the clinical data of patients who developed incisional complications and those who did not develop incisional complications after lumbar internal fixation, and investigate the risk factors for incisional complications in patients after lumbar internal fixation with posterior midline incision. A standardised data collection form was used to collect the clinical data of patients who were admitted and underwent lumbar internal fixation in our hospital from July 2018 to July 2021. Patients who experienced any one of the incisional complications, such as incision exudates, swelling, blisters, bruising, superficial/deep incisional infections, poor healing and scarring, after surgery were included in the incisional complication group, and patients who did not develop the above-mentioned incisional complications were included in the control group. Univariate logistic regression analysis was first performed to identify potential risk factors, significant factors from univariate analysis were then included in multivariable logistic regression analysis to identify independent risk factors for incisional complications after lumbar spine surgery. Among 455 patients included in the study, postoperative incision complications occurred in 82 patients, with an incidence rate of 18.02%. Multivariate regression analysis identified seven independent risk factors for incisional complications: age, body mass index, preoperative albumin level, hypertension, diabetes mellitus, operation time and local anaesthetic infiltration at the incision site after surgery. Our findings documented that age, body mass index, preoperative albumin level, hypertension, diabetes mellitus, operation time, and postoperative local anaesthetic infiltration at the incision site were risk factors for incisional complications after lumbar internal fixation with posterior median incision. Awareness of these risk factors can enable surgeons to develop a more appropriate perioperative management plan for patients undergoing lumbar internal fixation, thus helping them recover faster.

A tartrate-EDTA-Fe complex mediates electron transfer and enhances ammonia recovery in a bioelectrochemical-stripping system.

Traditional bioelectrochemical systems (BESs) coupled with stripping units for ammonia recovery suffer from an insufficient supply of electron acceptors due to the low solubility of oxygen. In this study, we proposed a novel strategy to efficiently transport the oxidizing equivalent provided at the stripping unit to the cathode by introducing a highly soluble electron mediator (EM) into the catholyte. To validate this strategy, we developed a new kind of iron complex system (tartrate-EDTA-Fe) as the EM. EDTA-Fe contributed to the redox property with a midpoint potential of -0.075 V (vs. standard hydrogen electrode, SHE) at pH 10, whereas tartrate acted as a stabilizer to avoid iron precipitation under alkaline conditions. At a ratio of the catholyte recirculation rate to the anolyte flow rate (RC-A) of 12, the NH4 +-N recovery rate in the system with 50 mM tartrate-EDTA-Fe complex reached 6.9 ±â€¯0.2 g N m-2 d-1, approximately 3.8 times higher than that in the non-EM control. With the help of the complex, our system showed an NH4 +-N recovery performance comparable to that previously reported but with an extremely low RC-A (0.5 vs. 288). The strategy proposed here may guide the future of ammonia recovery BES scale-up because the introduction of an EM allows aeration to be performed only at the stripping unit instead of at every cathode, which is beneficial for the system design due to its simplicity and reliability.

Novel Nomograms to Predict Delayed Hyponatremia After Transsphenoidal Surgery for Pituitary Adenoma.

Objective: This study aimed to develop a nomogram of clinical variables and magnetic resonance imaging scans to predict delayed hyponatremia after transsphenoidal surgery for pituitary adenoma. Methods: Patients who underwent transsphenoidal surgery for pituitary adenoma in Fuzong Clinical Medical College of Fujian Medical University between January 2012 and December 2020 were retrospectively investigated. Medical records, MRI findings, and laboratory examination results were recorded as candidate variable predictors of delayed hyponatremia. A nomogram to predict delayed hyponatremia was formulated based on the multivariable model of risk factors. The predictive accuracy and discriminative ability of the nomogram were assessed using the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analyses. The model underwent prospective validation in three medical centers with patients who underwent transsphenoidal surgery for pituitary adenoma between January 2021 and February 2022. Results: The model that incorporated the postoperative length of "measurable pituitary stalk," pituitary stalk deviation angle difference, postoperative diabetes insipidus, sinking depth of diaphragma sellae, and blood sodium level on the second postoperative day was developed and presented as the nomogram of the training cohort. The nomogram achieved area under the ROC curve (AUCs) of 0.806 and 0.849 for the training cohort and the testing cohort, respectively, and displayed good calibration. Decision curve analysis showed that the nomogram was clinically useful when the threshold probability was 13-96%. Conclusions: We developed a nomogram to evaluate the individualized prediction of delayed hyponatremia after transsphenoidal surgery for pituitary adenomas.

Efficacy, prognosis and safety analysis of anti-PD-1/PD-L1 inhibitor rechallenge in advanced lung cancer patients: a cohort study.

Background: The rechallenge of immune checkpoint inhibitors (ICI) is now an optional strategy for patients who discontinued ICI due to immune-related adverse events (irAEs) or disease progression. However, little data is available for the prognosis and prognostic factors of patients receiving ICI rechallenge treatment in advanced lung cancer patients. Our study aimed to explore the efficacy, prognosis and safety of patients who received anti-programmed cell death-1/programmed cell death ligand 1 (anti-PD-1/PD-L1) inhibitor rechallenge. Methods: In our retrospective cohort study, data of advanced lung cancer patients who received anti-PD-1/PD-L1 inhibitor and discontinued due to irAEs or disease progression were collected from December 2016 to August 2021. Enrolled patients were categorized into two groups: rechallenge group (R group) and non-rechallenge group (NR group). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety data were analyzed. Cox model and subgroup analysis were analyzed according to baseline characteristics, ICI type, the reason for discontinuing ICI, etc. According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), evaluation was performed routinely every 6-8 weeks after initiating treatment with the PD-1/PD-L1 inhibitor. The last follow-up in the study was on September 20, 2021. Results: Eighty-one patients who met our inclusion criteria were enrolled. In the whole cohort, the R group achieved better OS than the NR group [hazard ratio (HR) =0.176; 95% confidence interval (CI): 0.065-0.477; P=0.001). In the irAEs group, the survival analyses showed a trend toward improved OS in the rechallenge subgroup (HR =0.287; 95% CI: 0.081-1.025; P=0.055), and a promising DCR of 75% after an ICI rechallenge. Additionally, the exploration of safety outcomes indicated an acceptable recurrence rate (22.5%) of irAEs and an early onset of irAEs after an ICI rechallenge. In the disease progression group, the rechallenge subgroup did not improve OS (HR =0.214; 95% CI: 0.027-1.695; P=0.144), and the DCR of the rechallenge subgroup was 40% after ICI rechallenge. Conclusions: ICI rechallenge might be an attractive option for patients who discontinue treatment due to irAEs. For patients with disease progression, further research should be conducted. The recurrence of irAEs and their early onset during the second round of ICI should be considered.

Integrated constructed wetland and bioelectrochemistry system approach for simultaneous enhancment of p-chloronitrobenzene and nitrogen transformations performance.

Constructed wetlands (CWs) integrated with the bioelectrochemical system (BES-CW) to stimulate bio-refractory compounds removal holds particular promise, owing to its inherent greater scale and well-recognized environmentally benign wastewater advanced purification technology. However, the knowledge regarding the feasibility and removal mechanisms, particularly the potential negative effects of biorefractory compounds on nitrogen removal performance for the CWs is far insufficient. This study performed a critical assessment by using BES-CW (ECW) and conventional CW (CW) to investigate the effects of p-Chloronitrobenzene (pCNB) on nitrogen transformations in CWs. The results showed that low concentration (1 mg·L-1) of pCNB would inhibit the ammonia oxidation in CWs, while ECW could improve its tolerance to pCNB to a certain level (8 mg·L-1) due to the high pCNB degradation efficiencies (2.5 times higher than CWs), accordingly, much higher TN and nitrate removal efficiencies were observed in ECWs, 81.71% - 96.82% (TN) higher than CWs, further leading to a lower N2O emission from ECWs than CWs. The main intermediate of pCNB degradation was p-Chloroaniline (pCAN) and the genera Geobacter and Propionimicrobium were consider to be the responsible pCNB degradation bacteria in the present study. However, too high concentration (20 mg·L-1) of pCNB would have a huge impact on ECW and CW, especially microbial biomass. Nevertheless, ECW could improve the 1.87 times higher microbial biomass than CW on the substrate. Accordingly, considerably higher functional gene abundance was observed in ECW. Therefore, the introduction of BES has great potential to ensure CW stability when treating industrial wastewater containing bio-refractory compounds.

PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients.

Objectives: The objective of this study is to evaluate whether PIV (Pan-Immune-Inflammation Value) and PILE [a score derived from PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)] can predict clinical outcome of anti-PD-1/PD-L1 inhibitor combined with chemotherapy in patients with extensive-stage (ES) small cell lung cancer (SCLC). Methods: A total of 53 patients with ES-SCLC in the control group of clinical trial (NCT03041311) were included in this study. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE scores were composited based on PIV, LDH levels, and ECOG PS. The Kaplan-Meier method and Cox hazards regression models were used for survival analyses. Moreover, the predictive ability of PIV and PILE was validated in an independent real-world group consisting of 84 patients. Results: Patients in the low PIV group (PIV < median) had longer progression-free survival (PFS) and overall survival (OS) than those in the high PIV group (PIV ≥ median), along with the HR, which was 2.157 and 2.359, respectively (PFS HR 95% CI: 1.181-3.940, p = 0.012; OS HR 95% CI: 1.168-4.762, p = 0.020). High PILE score was observed relating to worse treatment efficacy (disease control rate (DCR): 84.21% vs. 100%, p = 0.047; durable clinical benefit (DCB) rate: 10% vs. 48.5%, p = 0.060) and poor clinical outcome (median PFS: 4.75 vs. 5.53 m, p = 0.043; median OS: 7.13 vs. 15.93 m, p = 0.002). Similar results were obtained about the predictive and prognostic abilities of PIV and PILE scores in the validation group. Conclusions: High PIV and high PILE were correlated with worse clinical outcomes in ES-SCLC patients treated with anti-PD-1/PD-L1 inhibitor combined with chemotherapy, reflecting that PIV and PILE might be useful to identify patients unlikely to benefit from anti-PD-1/PD-L1 therapy.

The Difference Between Preoperative and Postoperative Pituitary Stalk Deviation Angles Can Predict Delayed Hyponatremia After Transsphenoidal Surgery.

OBJECTIVE: Our aim was to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) for pituitary adenomas and analyze the effect of the difference between preoperative and postoperative pituitary stalk deviation angles on delayed hyponatremia. METHODS: A retrospective study was performed on the clinical data of patients with pituitary adenomas who were treated with TSS at a single institution. On the basis of the observation of indicators such as pituitary stalk deviation angle and length of "measurable pituitary stalk" on magnetic resonance imaging, we determined the predictors of postoperative delayed hyponatremia through univariate and multivariate analyses. RESULTS: Microscopic TSS was performed in 422 patients with pituitary adenoma, of whom 66 experienced postoperative delayed hyponatremia. Logistic regression analysis showed that the risk of delayed hyponatremia was greater for patients with a large difference between preoperative and postoperative pituitary stalk deviation angle (odds ratio = 1.040, 95% confidence interval: 1.018-1.051; P < 0.001) and a large difference in the "measurable pituitary stalk" (odds ratio = 1.128, 95% confidence interval: 1.011-1.258; P = 0.032), and patients with high blood sodium on the second day after surgery have a lower probability of developing delayed hyponatremia. CONCLUSIONS: This study is the first to suggest the important role of the difference between preoperative and postoperative pituitary stalk deviation angles in predicting the development of delayed hyponatremia after TSS for pituitary adenomas.

Down-regulation of MAPK pathway alleviates TRPV4-mediated trigeminal neuralgia by inhibiting the activation of histone acetylation.

Our objective of this study is to determine the molecular mechanism of MAPKs (mitogen activated protein kinase systems) on TRPV4 (transient receptor potential vanilloid 4)-mediated trigeminal neuralgia (TN). Partial chronic constriction injury of the infraorbital nerve (CCI-ION) ligation model was used in this research. When treated with antagonists of p38, JNK or ERK, the mechanical hyperalgesia threshold, nerve fiber disorder, myelinoclasis, and Schwann cells proliferation could be reversed. RT-PCR (real-time quantitative polymerase chain reaction), Western blot and IHC (immunohistochemistry) showed that TRPV4 mRNA and protein levels, TRPV4-positive cells and small positive neurons decreased remarkably in TN group treated with antagonists of p38, JNK or ERK. ELISA (enzyme-linked immunosorbent assay) was performed to discover inhibition of MAPK pathway can down-regulate the expression of HATs (histone acetyltransferases), and up-regulate the expression of HDACs (histone deacetylases) in TN, thus inhibiting histone acetylation. Finally, Western blot was performed to identify the phosphorylation status of p38, JNK and ERK, finding decreased phosphorylation forms in antagonists treated TN groups compared with TN groups. Based on the above investigation method, on a whole, our study showed that down-regulation of MAPK pathway could alleviate TRPV4-mediated trigeminal neuralgia, via inhibiting the activation of histone acetylation.

Influence of Patellar Morphology Classified by Wiberg Classification on Knee Joint Function and Patellofemoral Tracking After Total Knee Arthroplasty Without Patellar Resurfacing.

BACKGROUND: To evaluate the influence of patellar morphology on knee joint function and patellofemoral tracking in patients with primary osteoarthritis after total knee arthroplasty (TKA) without patellar resurfacing. METHODS: We performed a retrospective study of 156 patients with primary osteoarthritis who underwent TKA without patellar resurfacing from April 2018 to July 2019. As per Wiberg classification, patients were divided into Wiberg type I (group A, n = 38), II (group B, n = 88), and III (group C, n = 30) groups. The clinical data, postoperative follow-up data, and radiological data between three groups were compared. RESULTS: There was no statistically significant difference in the HSS score and Feller score between the three groups before surgery and at each follow-up point after surgery (P > .05). At the last follow-up, there were no significant differences in the height and relative thickness of the patella between the three groups (P > .05). However, the incidence of anterior knee pain was significantly higher in group C than in the group B (P < .05). The patellar tilt angle was significantly larger in group C than in the groups A and B (both P < .05). The patellar facet angle was significantly larger in group A than in group B and C, which was also significantly larger in group B than in group C (both P < .05). CONCLUSION: Patients with three different morphologic types of the patella both exhibited improved knee joint function after TKA, however, patients with Wiberg type Ⅲ patella were more prone to have poor patellofemoral tracking and anterior knee pain after surgery.

EGFR/BRAF/MEK co-inhibition for EGFR-mutated lung adenocarcinoma patients with an acquired BRAFV600E mutation: a case report and review of literature.

Despite the promising initial anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), most advanced non-small-cell lung cancers (NSCLCs) progress eventually due to therapeutic resistance. V-Raf murine sarcoma viral oncogene homolog B1 (BRAF)V600E mutation has been considered as an uncommon mutation that contributes to acquired resistance for EGFR-TKIs. In the presented case, BRAFV600E mutation was detected as an acquired resistance-mediated mutation in a patient treated with osimertinib (a third-generation EGFR-TKI). The presented patient achieved partial regression and ongoing PFS of four months after the co-inhibition of osimertinib plus dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Our case further enriches the clinical evidence of the efficacy of EGFR/BRAF/MEK co-inhibition in patients with an acquired BRAFV600E mutation, consistent with the review of the literature (eight cases). Additionally, our case highlights the important role of sample type, method, and platform of gene detection in patient management, life quality, and prognosis, as well as the understanding of acquired resistance mechanism.

Case Report: A 91-Year-Old Patient With Non-Small Cell Lung Cancer Harboring MET Y1003S Point Mutation.

BACKGROUND: The Y1003S point mutation in exon 14 of mesenchymal-epithelial transition (MET) is a rare mutation that can lead to oncogenic transformation. Few data are available on the characteristics of this mutation. This report presents an elderly patient with non-small cell lung cancer (NSCLC) and a Y1003S mutation in MET detected by next-generation sequencing (NGS). CASE REPORT: In October 2020, a 91-year-old male was admitted to the Department of Respiratory and Critical Care Medicine, Ruijin Hospital because of an increased carcinoembryonic antigen. Imaging revealed highly suspicious lesions in the right upper lobe of the lung, right apex, and left upper lobe with traction of the adjacent pleura. The patient was histologically confirmed as having adenocarcinoma and the MET Y1003S mutation was detected by the NGS subsequently. After evaluation, the patient started crizotinib treatment in December 2020. In the first assessment of tumor response, a chest CT scan in January 2021 showed a partial response. The patient experienced a pulmonary embolism and an abnormal liver function during the treatment and recovered after symptomatic treatment. He maintained a partial response in the last available assessment in July 2021, with the right upper lung lesion being 26 × 9 mm. CONCLUSION: The MET Y1003S mutation was detected in this case, and the patient achieved a partial response using crizotinib. This case highlighted the role of NGS in detecting a rare mutation. Successful remission of complications in such an elderly patient necessitates careful and timely management.