Correlation among post-surgery recurrence of CRSwNP and TCM syndromes and tissue inflammatory cell infiltration type: a study protocol.

BACKGROUND: Functional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types. METHODS AND ANALYSIS: This is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People's Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients' pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches. DISCUSSION: This is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ChiCTR2100041646.

Ganoderma lucidum spores-derived particulate ß-glucan treatment improves antitumor response by regulating myeloid-derived suppressor cells in triple-negative breast cancer.

Granular ß-1,3-glucan extracted from the wall of Ganoderma lucidum spores, named GPG, is a bioregulator. In this study, we investigated the structural, thermal, and other physical properties of GPG. We determined whether GPG ameliorated immunosuppression caused by Gemcitabine (GEM) chemotherapy. Triple-negative breast cancer mice with GPG combined with GEM treatment had reduced tumor burdens. In addition, GEM treatment alone altered the tumor microenvironment(TME), including a reduction in antitumor T cells and a rise in myeloid-derived suppressor cells (MDSC) and regulatory T cells (Tregs). However, combined GPG treatment reversed the tumor immunosuppressive microenvironment induced by GEM. GPG inhibited bone marrow (BM)-derived MDSC differentiation and reversed MDSC expansion induced by conditioned medium (CM) in GEM-treated E0771 cells through a Dectin-1 pathway. In addition, GPG downgraded PD-L1 and IDO1 expression on MDSC while boosting MHC-II, CD86, TNF-α, and IL-6 expression. In conclusion, this study demonstrated that GPG could alleviate the adverse effects induced by GEM chemotherapy by regulating TME.

Circ_100549 promotes tumor progression in lung adenocarcinoma through upregulation of BIRC6.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer with high incidence and mortality globally. Emerging evidence suggests that circular RNAs (circRNAs) exert critical functions in human cancers, including LUAD. CircRNA_100549 (circ_100549) has been reported to be significantly upregulated in non-small cell lung cancer (NSCLC) samples, while its role in modulating LUAD progression remains to be explored. The current study aims at investigating the functional roles of circ_100549 in LUAD and its downstream molecular mechanism. First, we found that the expression of circ_100549 was higher in LUAD cell lines. Loss-of-function assays verified that depletion of circ_100549 repressed LUAD cell proliferation but accelerated cell apoptosis. Furthermore, in vivo experiments demonstrated that silencing of circ_100549 suppressed tumor growth. Subsequently, based on database analysis, we carried out a series of experiments to explore the mechanisms and effects of circ_100549 underlying LUAD progression, including RNA-binding protein immunoprecipitation (RIP), RNA/DNA pull-down, luciferase reporter, and chromatin immunoprecipitation (ChIP) assays. The results indicated that circ_100549 serves as a ceRNA by sponging miR-95-5p to upregulate BPTF expression, thus upregulating BIRC6 expression at a transcriptional level in LUAD. In summary, our study demonstrated that circ_100549 facilitates LUAD progression by upregulating BIRC6 expression.

Modular Edge Analysis Reveals Chemotherapy-induced Brain Network Changes in Lung Cancer Patients.

BACKGROUND: Lung cancer patients with post-chemotherapy may have disconnected or weakened function connections within brain networks. OBJECTIVE: This study aimed to explore the abnormality of brain functional networks in lung cancer patients with post-chemotherapy by modular edge analysis. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 40 patients after chemotherapy, 40 patients before chemotherapy and 40 normal controls. Patients in all three groups were age and sex well-matched. Then, modular edge analysis was applied to assess brain functional network alterations. RESULTS: Post-chemotherapy patients had the worst MoCA scores among the three groups (p < 0.001). In intra-modular connections, compared with normal controls, the patients after chemotherapy had decreased connection strengths in the occipital lobe module (p < 0.05). Compared with the nonchemotherapy group, the patients after chemotherapy had decreased connection strengths in the subcortical module (p < 0.05). In inter-modular connections, compared with normal controls, the patients after chemotherapy had decreased connection strength in the frontal-temporal lobe modules (p < 0.05). Compared with the non-chemotherapy group, the patients after chemotherapy had decreased connection strength in the subcortical-temporal lobe modules (p < 0.05). CONCLUSION: The results reveal that chemotherapy can disrupt connections in brain functional networks. As far as we know, the use of modular edge analysis to report changes in brain functional brain networks associated with chemotherapy was rarely reported. Modular edge analysis may play a crucial part in predicting the clinical outcome for the patients after chemotherapy.

N6-Methyladenosine Modification of lncCCKAR-5 Regulates Autophagy in Human Umbilical Cord Mesenchymal Stem Cells by Destabilizing LMNA and Inhibits Diabetic Wound Healing.

Long noncoding RNAs are pivotal contributors to the development of human diseases. However, their significance in the context of diabetic wound healing regulated by human umbilical cord mesenchymal stem cells (hUCMSCs) remains unclear. This study sheds light on the involvement of lncCCKAR5 in this process. We found that hUCMSCs exposed to high glucose conditions exhibited a significant downregulation of lncCCKAR5 expression, and lncCCKAR5 played a critical role in modulating autophagy, thus inhibiting apoptosis in hUCMSCs. In addition, the reduction of lncCCKAR5 in cells exposed to high glucose effectively thwarted cellular senescence and facilitated filopodium formation. Mechanistically, lncCCKAR5 served as a scaffold that facilitated the interaction between MKRN2 and LMNA, a key regulator of cytoskeletal function and autophagy. The lncCCKAR5/LMNA/MKRN2 complex played a pivotal role in promoting the ubiquitin-mediated degradation of LMNA, with this effect being further augmented by N6-adenosine methylation of lncCCKAR5. Consequently, our findings underscore the critical role of lncCCKAR5 in regulating the autophagic process in hUCMSCs, particularly through protein ubiquitination and degradation. This intricate regulatory network presents a promising avenue for potential therapeutic interventions in the context of diabetic wound healing involving hUCMSCs.

Six-point scleral fixation of a three-looped haptics one-piece posterior chamber intraocular lens by a single suture.

To evaluate a novel technique for six-point scleral fixation of a three-looped haptics posterior chamber intraocular lens (PCIOL) by a single suture. Nine eyes of nine patients were studied from September 2021 to March 2023. All patients had undergone vitrectomy. Only a single 9-0 polypropylene suture was used for scleral fixation. The three looped haptics were fixed at 12, 4, and 8 o'clock with six-point scleral fixation. The entire procedure took about 30 min. Among the nine patients, eight (88.8%) eyes had a significant improvement in best-corrected visual acuity, whereas one (11.2%) eye showed no change. No intraoperative or postoperative complications were observed. By ultrasonic biomicroscopy examination, intraocular lenses were well positioned and stable with no tilt in the horizontal and vertical axis. The method of six-point scleral fixation of a three-looped haptics PCIOL by a single suture is safe and effective.

Comparison of the efficacy and adverse effects of unilateral or bilateral botulinum toxin injections for adductor spasmodic dysphonia: a systematic review and meta-analysis.

PURPOSE: This study aims to aggregate and analyze existing clinical evidence to compare the efficacy and adverse effects of unilateral or bilateral botulinum toxin injections for the treatment of adductor spasmodic dysphonia (ADSD). METHODS: Reports from non-randomized controlled trials and cohort studies pertaining to the efficacy and adverse effects of unilateral and bilateral botulinum toxin injections for ADSD were identified and retrieved from four electronic databases from inception to July 2023. The meta-analysis employed fixed or random effects models to assess pooled relative risks (RR), mean differences (MDs), and standard mean differences (SMDs) with their corresponding 95% confidence intervals (CIs). RESULTS: We included two non-randomized controlled trials and seven cohort studies comprising 854 total patients. Meta-analysis of the included studies showed that bilateral botulinum toxin injections associated with a longer duration of vocal improvement (MD = - 2.89, 95% CI - 3.13 to - 2.65, I2 = 0%, P < 0.00001). However, bilateral botulinum toxin injections associated with an increase in adverse effects, including a longer duration of breathy voice quality (SMD = - 0.51, 95% CI - 0.79 to - 0.22, I2 = 35%, P = 0.0005) and a higher occurrence of swallowing difficulties (RR = 0.46, 95% CI 0.35 to 0.11, I2 = 0%, P < 0.00001). CONCLUSION: Bilateral botulinum toxin injections for ADSD showed a longer duration of vocal improvement, a longer breathy voice duration and a higher dysphagia occurrence and duration than unilateral injections.

Promote lipolysis in white adipocytes by magnetic hyperthermia therapy with Fe3O4microsphere-doped hydrogel.

Obesity has become an ongoing global crisis, since it increases the risks of cardiovascular disease, type 2 diabetes, fatty liver, cognitive decline, and some cancers. Adipose tissue is closely associated with the disorder of lipid metabolism. Several efforts have been made toward the modulation of lipid accumulation, but have been hindered by poor efficiency of cellular uptake, low safety, and uncertain effective dosage. Herein, we design an Fe3O4microsphere-doped composite hydrogel (Fe3O4microspheres @chitosan/ß-glycerophosphate/collagen), termed as Fe3O4@Gel, as the magnetocaloric agent for magnetic hyperthermia therapy (MHT), aiming to promote lipolysis in white adipocytes. The experimental results show that the obtained Fe3O4@Gel displays a series of advantages, such as fast sol-gel transition, high biocompatibility, and excellent magneto-thermal performance. MHT, which is realized by Fe3O4@Gel subjected to an alternating magnetic field, leads to reduced lipid accumulation, lower triglyceride content, and increased mitochondrial activity in white adipocytes. This work shows that Fe3O4@Gel-mediated MHT can effectively promote lipolysis in white adipocytesin vitro, which provides a potential approach to treat obesity and associated metabolic disorders.

Update on the outcome of M-protein screening program of multiple myeloma in China: A 7-year cohort study.

BACKGROUND: To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. METHODS: The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. RESULTS: There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9 months, p < 0.001, HR: 2.12, 95% CIs: 1.69-2.65), with median follow-ups of 32.6 and 27.4 months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3 months, p < 0.001, HR: 2.49, 95% CIs: 1.81-3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screening-driven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. CONCLUSION: Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes.

Minimal Posterior Pole Vitrectomy and Fixing the Inverted Internal Limiting Membrane Flap with DisCoVisc for Macular Hole: No Gas or Air Tamponade.

PURPOSE: To investigate an alternative surgical method for macular hole repair without fluid-air exchange, gas tamponade, and prone positioning. METHODS: Eighteen eyes of 17 patients with macular holes underwent minimal posterior pole vitrectomy with an inverted internal limiting membrane flap technique. Ophthalmic viscosurgical device was used to fix the inverted internal limiting membrane flap in the balanced salt solution. No fluid-air exchange, gas tamponade, or prone positioning was needed. Follow-ups were performed at 1 day, 1 week, and the last visit (ranging from 3 to 6 months) after surgery. Optical coherence tomography examination, intraocular pressure, and best-corrected visual acuity measurements were performed preoperatively and at every follow-up, postoperatively. RESULTS: Primary closure of the macular hole was observed in all 18 eyes (100%). Optical coherence tomography showed U-type closure in 12 eyes, V-type closure in five eyes, and W-type closure in one eye. Preoperative, postoperative 1 week, and last follow-up best-corrected visual acuity were 0.90 (Snellen equivalent 20/159) ± 0.31 LogMAR, 0.72 (Snellen equivalent 20/105) ± 0.33 LogMAR, and 0.48 (Snellen equivalent 20/60) ± 0.32 LogMAR, respectively. Postoperative visual acuity was significantly improved compared with preoperative values ( F = 19.250, P = 0.000). No significant difference in intraocular pressure was found compared with preoperative values ( F = 1.933, P = 0.168). No significant complications were observed. CONCLUSION: This surgical method can effectively close macular holes, improve visual acuity, enhance surgical efficiency, reduce surgical complications, and improve patients' postoperative experience without the need for fluid-air exchange, gas tamponade, or prone positioning.

G protein-coupled estrogen receptor 1 deficiency impairs adult hippocampal neurogenesis in mice with schizophrenia.

OBJECTIVE: This study aimed to confirm that G protein-coupled estrogen receptor 1 (GPER1) deficiency affects cognitive function by reducing hippocampal neurogenesis via the PKA/ERK/IGF-I signaling pathway in mice with schizophrenia (SZ). METHODS: Mice were divided into four groups, namely, KO Con, WT Con, KO Con, and WT SZ (n = 12 in each group). All mice were accustomed to the behavioral equipment overnight in the testing service room. The experimental conditions were consistent with those in the animal house. Forced swimming test and Y-maze test were conducted. Neuronal differentiation and maturation were detected using immunofluorescence and confocal imaging. The protein in the PKA/ERK/IGF-I signaling pathway was tested using Western blot analysis. RESULTS: GPER1 KO aggravated depression during forced swimming test and decreased cognitive ability during Y-maze test in the mouse model of dizocilpine maleate (MK-801)-induced SZ. Immunofluorescence and confocal imaging results demonstrated that GPER1 knockout reduced adult hippocampal dentate gyrus neurogenesis. Furthermore, GPER1-KO aggravated the hippocampal damage induced by MK-801 in mice through the PKA/ERK/IGF-I signaling pathway. CONCLUSIONS: GPER1 deficiency reduced adult hippocampal neurogenesis and neuron survival by regulating the PKA/ERK/IGF-I signaling pathway in the MK-801-induced mouse model of SZ.

Case report: Endoscopic frontal sinus opening surgery for noninflammatory frontal sinus headache: A short case series.

Objective: The objectives of this study were to analyze rhinogenic headache, i.e., noninflammatory frontal sinus headache, a headache caused by bony obstruction of the frontal sinus drainage channels that receives relatively insufficient attention clinically, and to propose endoscopic frontal sinus opening surgery as a treatment based on the etiology. Study Design: Case series. Setting: From the data of patients with noninflammatory frontal sinus headache who underwent endoscopic frontal sinus surgery in Hospital of Chengdu University of Traditional Chinese Medicine during 2016-2021, data for three cases with detailed postoperative follow-up data were extracted for case series reports. Methods: This report provides detailed information on three patients with noninflammatory frontal sinusitis headache. Treatment options include surgery and rechecking, with the visual analogue scale (VAS) scores of preoperative and postoperative symptoms, CT, and endoscopic images. Three patients had common characteristics: the clinical manifestations were recurrent or persistent with pain and discomfort in the forehead area, but there was no nasal obstruction or runny nose; the paranasal sinus CT revealed no signs of inflammation in the sinuses but suggested bony obstruction of the drainage channel of the frontal sinus. Results: All three patients had recovery from headache, nasal mucosal recovery, and patent frontal sinus drainage. The recurrence rate of forehead tightness and discomfort or pain was 0. Conclusion: Noninflammatory frontal sinus headache does exist. Endoscopic frontal sinus opening surgery is a feasible treatment modality that can largely or even completely eliminate the stuffy swelling and pain in the forehead. The diagnosis and surgical indications for this disease are based on a combination of anatomical abnormalities and clinical symptoms.

Astaxanthin suppresses oxidative stress and calcification in vertebral cartilage endplate via activating Nrf-2/HO-1 signaling pathway.

BACKGROUND: Cartilage endplate (CEP) degeneration is an important initiating factor leading to intervertebral disc degeneration (IVDD). Astaxanthin (Ast) is a natural lipid-soluble and red-orange carotenoid which possesses various biological activities, including antioxidant, anti-inflammatory, and anti-aging effects in multiple organisms. However, the effects and mechanism of Ast on endplate chondrocytes remain largely unknown. The objective of the current study was to investigate the effects and of Ast on CEP degeneration and its underlying molecular mechanisms. METHODS: Tert-butyl hydroperoxide (TBHP) was used to mimic the IVDD pathological environment. We investigated the effects of Ast on the Nrf2 signaling pathway and damage-associated events. The IVDD model was constructed by surgical resection of L4 posterior elements to explore the role of Ast in vivo. RESULTS: We found that the activation of the Nrf-2/HO-1 signaling pathway was enhanced by Ast, thus promoted mitophagy process, inhibited oxidative stress and CEP chondrocytes ferroptosis, eventually ameliorated extracellular matrix (ECM) degradation, CEP calcification and endplate chondrocytes apoptosis. Knockdown of Nrf-2 using siRNA inhibited Ast induced mitophagy process and its protective effect. Moreover, Ast inhibited oxidative stimulation-induced NF-κB activity and could ameliorate the inflammation response. The results also were confirmed by experiments in vivo, Ast alleviated IVDD development and CEP calcification. CONCLUSIONS: Ast could protect vertebral cartilage endplate against oxidative stress and degeneration via activating Nrf-2/HO-1 pathway. Our results imply that Ast may serve as a potential therapeutic agent for IVDD progression and treatment.

Clinical Characteristics of Minimal Lumbar Disc Herniation and Efficacy of Percutaneous Endoscopic Lumbar Discectomy via Transforaminal Approach: A Retrospective Study.

OBJECTIVE: To define the characteristics of Mini LDH, develop new diagnostic references and examine the clinical efficacy of percutaneous endoscopic lumbar discectomy via a transforaminal approach (TF-PELD) for it. METHODS: A total of 72 patients who underwent TF-PELD with Mini LDH from September 2019 to October 2022 were enrolled in this retrospective study. The patients' basic information, symptoms, number of outpatient visits, duration of conservative treatment, physical examination findings and so on were obtained from the medical records. Clinical effects of TF-PELD for Mini LDH were assessed by means of the following: the Visual Analog Scale (VAS) for low back pain (LBP) and leg pain, Oswestry Disability Index (ODI) for functional status assessment and Modified Mac Nab criteria for patient satisfaction. RESULTS: Mini LDH have specific clinical characteristics and imaging features. All included patients achieved obvious pain relief after TF-PELD surgery. Pain scores were repeated at postoperative day 1 and 1, 3, 6, 12 and 24 months later. Results were statistically analyzed. The average VAS-Back, VAS-Leg and ODI scores were all significantly reduced at the first postoperative day and gradually decreased with the follow-up time continuing. In total, 66 out of 72 patients received an excellent or good recovery and no poor result was reported according to the Modified Mac Nab criteria. CONCLUSIONS: Mini LDH is a type of LDH with special characteristics and in need of correct diagnosis and active treatment in clinical work. TF-PELD was also found to be an effective procedure for the treatment of Mini LDH.

Pathogenic free-living amoebic encephalitis from 48 cases in China: A systematic review.

Background: Free-living amoebae (FLA) including Naegleria fowleri, Acanthamoeba spp., and Balamuthia mandrillaris can become pathogenic and cause severe cerebral infections, named primary amoebic meningoencephalitis (PAM), granulomatous amoebic encephalitis (GAE), and balamuthia amoebic encephalitis (BAE), respectively. FLA encephalitis has been reported across China, but the clinical data descriptions and analytical results of these different reports vary widely. Currently, no consensus treatment has been established. We conduct a systematic review to evaluate the exposure location, clinical symptoms, diagnosis, treatment, and prognosis of three FLA encephalitis and aim to reveal the differences between three FLA encephalitis in China. Methods: We used MEDLINE (PubMed interface), EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang database, and China Biology Medicine disc (CBMdisc) databases for literatures published and manually retrieve the hospital records of our hospital. The search time was up to August 30, 2022, with no language restrictions. Results: After excluding possible duplicate cases, a total of 48 patients of three FLA encephalitis were collected. One from the medical records of our hospital and 47 patients from 31 different studies. There were 11 patients of PAM, 10 patients of GAE, and 27 patients of BAE. The onset of PAM is mostly acute or subacute, and the clinical symptoms are acute and fulminant hemorrhagic meningoencephalitis. Most patients with GAE and BAE have an insidious onset and a chronic course. A total of 21 BAE patients (77.8%) had skin lesions before onset of symptoms. Additionally, 37 cases (77.1%) were diagnosed with FLA encephalitis before death. And there were 4 of PAM, 2 of GAE, and 10 of BAE diagnosed using next generation sequencing. No single agent can be proposed as the ideal therapy by itself. Only 6 cases were successfully treated. Conclusions: This review provides an overview of the available data and studies of FLA encephalitis in China and identify some potential differences. FLA encephalitis is a rare but pathogenic infection, and physicians should early identify this encephalitis to improve survival.

The evolving diagnosis and treatment paradigms of multiple myeloma in China: 15 years' experience of 1256 patients in a national medical center.

BACKGROUND: Significant advances in multiple myeloma (MM) over the past 15 years led to exciting changes in the management of MM patients in China, which in turn brought about the early diagnoses, precise risk stratifications, and improved prognoses. METHODS: We summarized the dynamic changes in the management of newly diagnosed (ND) MM in a national medical center, crossing the old and novel drug era. Demographics, clinical characteristics, first-line treatment, response rate, and survival were retrospectively collected among NDMMs diagnosed in Zhongshan Hospital Fudan University from January 2007 to October 2021. RESULTS: Of the 1256 individuals, median age was 64 (range 31-89) with 45.1% patients >65 years. About 63.5% were male, 43.1% were at ISS stage III and 9.9% had light-chain amyloidosis. Patients with abnormal ratio of free light chain (80.4%), extramedullary disease (EMD, 22.0%), and high-risk cytogenetic abnormalities (HRCA, 26.8%) were detected by novel detection techniques. The best confirmed ORR was 86.5%, including 39.4% with CR. Short- and long-term PFS and OS rates persistently increased each year along with increasing novel drug applications. Median PFS and OS were 30.9 and 64.7 months. Advanced ISS stage, HRCA, light-chain amyloidosis and EMD independently predicted an inferior PFS. First-line ASCT indicated a superior PFS. Advanced ISS stage, elevated serum LDH, HRCA, light-chain amyloidosis, and receiving PI/IMiD-based regimen versus PI+IMiD-based regimen independently indicated a poorer OS. CONCLUSIONS: In brief, we illustrated a dynamic landscape of MM patients in a national medical center. Chinese MM patients evidently benefited from newly introduced techniques and drugs in this field.

A lung squamous cell carcinoma-associated membranous nephropathy patient free of tumor and membranous nephropathy after the treatment of surgery and radiochemotherapy following pembrolizumab: A rare case report.

RATIONALE: Membranous nephropathy (MN) is an autoimmune disease, which is classified into primary and secondary MN. Malignancy-associated MN (M-MN) accounts for about 10% of secondary MN cases. Lung cancer is the most common type of malignancy among M-MN patients. Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1) have showed promising efficacy and good safety in many types of solid tumors, including non-small cell lung cancer. To date, whether ICIs could be a treatment option for M-MN patients with PD-L1 expression and or high tumor mutation burden (TMB) level has not been documented. PATIENT CONCERNS: A 68-year-old male patient presented with edema of the lower limbs with increased urine foam in August 2018. Biopsy on the right kidney showed MN at stage I with subepithelially localized immune deposits. DIAGNOSIS: Lung squamous cell carcinoma (LSCC)-associated MN with PD-L1 expression (20%) and high TMB level (26.2 mutations/Mb). INTERVENTIONS: The patient received immunosuppressive therapy targeting the initially diagnosed primary MN as first-line treatment plus surgery and radiochemotherapy following pembrolizumab targeting the definitively diagnosed lung cancer as second-line treatment. OUTCOMES: The patient benefited from radiochemotherapy following pembrolizumab (lasting more than 38 months) rather than immunosuppressive therapy. LESSONS: Our work suggests that combined ICIs might be an effective treatment option for M-MN patients who harbor PD-L1 expression. Our work highlights that the presence of malignancy should not be neglected at the initial diagnosis of MN.

Clinical value of the renal pathologic scoring system in complement-mediated thrombotic microangiopathy.

OBJECTIVES: This study was initiated to establish a renal thrombotic microangiopathy (TMA) scoring system based on clinical needs and investigate its predictive value for patients' long-term outcomes. METHODS: Kidney biopsy-proven Complement-mediated TMA (C-TMA) patients from January 2000 to December 2017 in Peking University First Hospital were retrospectively studied. Both acute and chronic TMA-related lesions, including 15 pathologic indices, were semiquantitatively scored. The interobserver and intraobserver reproducibility and correlation between the pathologic indices and clinical parameters were analyzed. Furthermore, the patients were divided into 2 groups by dialysis use at baseline, and the association of these pathologic indices with their prognostic outcomes was assessed between the two groups. RESULTS: Ninety-two patients with renal biopsy-proven C-TMA were enrolled. All fifteen included pathology indices showed good or moderate interobserver and intraobserver reproducibility and correlated well with several clinical parameters. Several clinicopathological indices were worse in the dialysis group than in the nondialysis group, such as serum creatinine, hemoglobin, platelet count, and estimated glomerular filtration rate. Moreover, morphologic features in the dialysis group presented with more severe vascular lesions. Interstitial fibrosis and chronic tubulointerstitial lesions were related to a trend of high risk of continuous dialysis in the dialysis group. Based on univariate and multivariable Cox regression analysis, more severe glomerular lesions, including glomerular mesangiolysis, glomerular basement membrane double contours and glomerular mesangial proliferation, were identified as risk factors predicting worse prognosis. CONCLUSIONS: Our renal C-TMA semiquantitative scoring system is reliable with good reproducibility and prognostic value in clinical practice, which needs further validation.

The enzyme activity of sortase A is regulated by phosphorylation in Staphylococcus aureus.

In many Gram-positive bacteria, the transpeptidase enzyme sortase A (SrtA) anchors surface proteins to cell wall and plays a critical role in the bacterial pathogenesis. Here, we show that in Staphylococcus aureus, an important human pathogen, the SrtA is phosphorylated by serine/threonine protein kinase Stk1. S. aureus SrtA can also be phosphorylated by small-molecule phosphodonor acetyl phosphate (AcP) in vitro. We determined that various amino acid residues of S. aureus SrtA are subject to phosphorylation, primarily on its catalytic site residue cysteine-184 in the context of a bacterial cell lysate. Both Stk1 and AcP-mediated phosphorylation inhibited the enzyme activity of SrtA in vitro. Consequently, deletion of gene (i.e. stp1) encoding serine/threonine phosphatase Stp1, the corresponding phosphatase of Stk1, caused an increase in the phosphorylation level of SrtA. The stp1 deletion mutant mimicked the phenotypic traits of srtA deletion mutant (i.e. attenuated growth where either haemoglobin or haem as a sole iron source and reduced liver infections in a mouse model of systemic infection). Importantly, the phenotypic defects of the stp1 deletion mutant can be alleviated by overexpressing srtA. Taken together, our finding suggests that phosphorylation plays an important role in modulating the activity of SrtA in S. aureus.

Identification of an Exosome-relevant SNHG6-hsa-miR-429- CHRDL1/CCNA2 Axis for Lung Adenocarcinoma Prognosis Evaluation.

AIM: To explore an exosome-relevant molecular classification in lung adenocarcinoma (LUAD). BACKGROUND: Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined. OBJECTIVE: Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation. METHODS: MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis. RESULTS: Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects. CONCLUSION: Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.