The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer.

GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor's structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.

Intraoperative Protection of Pharyngeal Autonomic Nerves: Preventing Dysphagia After Anterior Cervical Decompression and Fusion Surgery.

OBJECTIVE: The study aims to investigate whether intraoperative protection of the pharyngeal autonomic nerve can effectively reduce the incidence of postoperative dysphagia following anterior cervical decompression and fusion surgery (ACDF). METHODS: A retrospective analysis was conducted on 130 cases that underwent ACDF from January 2018 to June 2022 at our hospital. Divided into nonautonomic neuroprotection (NANP) group and autonomic neuroprotection group based on whether receive protective measures for the pharyngeal autonomic nerve during surgery. General data were recorded and compared between the 2 groups. Postoperative outcomes were evaluated using Neck Disability Index, Japanese Orthopaedics Association (JOA) score, and JOA improvement rate. The incidence and severity of postoperative dysphagia were assessed using Bazaz dysphagia assessment criteria and swallowing-quality of life questionnaire. RESULTS: There were no significant differences in general data (P > 0.05). The average operation time and intraoperative blood loss also showed no significant differences (P > 0.05). Both groups showed significant improvements in Neck Disability Index and JOA scores at all follow-up time points compared to preoperative scores (P < 0.01). The incidence of postoperative dysphagia in the autonomic neuroprotection group was significantly lower than that in the NANP group at all follow-up time points (P < 0.05). Both group showed a significant reduction in scores 3 days postoperatively compared to preoperative scores (P < 0.01), and the NANP group also showed significant reductions in scores at 3 month and 1 year postoperative follow-up time points compared to preoperative scores (P < 0.01). CONCLUSIONS: The adoption of pharyngeal autonomic nerve protective measures during ACDF can effectively lower the probability of postoperative dysphagia.

Channel-assisted cervical key hole technology combined with ultrasonic bone osteotome versus posterior percutaneous endoscopic cervical foraminotomy: a clinical retrospective study.

PURPOSE: The search for more effective and safe treatment methods for cervical spondylotic radiculopathy (CSR) has led to the rapid development and increasing popularity of minimally invasive posterior cervical foraminotomy (MI-PCF). This study aims to compare two important approaches for MI-PCF surgery: the channel-assisted cervical key hole technology combined with ultrasonic bone osteotome (CKH-UBO) and posterior percutaneous endoscopic cervical foraminotomy (PPECF). METHODS: Data from patients treated with single-level CKH-UBO (n = 35) or PPECF (n = 40) were analyzed. Clinical outcomes, including visual analogue scale (VAS) scores for neck and arm pain, Neck Disability Index (NDI), and modified Macnab criteria, were assessed preoperatively, as well as at three days, three months, and one year postoperatively. RESULTS: The percentages of patients with excellent and good outcomes were 97.14% and 92.5%, respectively. The average surgical time in the CKH-UBO group was significantly shorter than in the PPECF group (p < 0.001), while the average incision length in the PPECF group was significantly smaller than in the CKH-UBO group. There were no significant differences between the two groups in terms of blood loss, hospital stay, and clinical outcomes at three days, three months, and 12 months postoperatively. CONCLUSION: CKH-UBO can achieve the same surgical outcomes as PPECF for the treatment of CSR. However, CKH-UBO saves more time but requires patients to undergo larger incisions.

Clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of II° lumbar isthmic spondylolisthesis: A retrospective cohort study.

Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is not suitable for high-grade isthmic spondylolisthesis, whether MIS-TLIF can treat II° lumbar isthmic spondylolisthesis (IS) is still controversial. This retrospective cohort study compared the clinical efficacy of MIS-TLIF and open transforaminal lumbar interbody fusion (OPEN-TLIF) in the treatment of II° lumbar IS. From January 2017 to January 2023, 101 patients with II° lumbar IS were diagnosed in our hospital and underwent surgical treatment, of which 53 received MIS-TLIF surgery and 48 received OPEN-TLIF surgery. The operation time, blood loss and surgical complications were compared between the 2 groups. The pain, function, reduction rate and fusion rate of the patients were evaluated during follow-up. The amount of intraoperative blood loss, postoperative drainage, and postoperative hospital stay in the MIS-TLIF group were significantly lower than those in the OPEN-TLIF group were (P < .01). In the MIS-TLIF group, there were 1 case of dural sac injury and 3 cases of lower limb paralysis. The complication rate of MIS-TLIF was lower than the OPEN-TLIF group (P = .032). In the visual analog scale score of low back pain, the MIS-TLIF group was lower than the OPEN-TLIF group after operation and at the last follow-up. There were no significant differences in postoperative leg pain score, slippage rate, and fusion rate between the 2 groups. Compared with OPEN-TLIF, MIS-TLIF has the advantages of better low back pain relief, less trauma, less bleeding and faster recovery, and is worthy of clinical promotion.

Gender-specific associations between mixture of polycyclic aromatic hydrocarbons and telomere length.

Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .

The clinicopathological and immunohistochemical features of breast carcinomas with signet-ring-cell differentiation.

BACKGROUND: This study investigated the clinicopathological features, immunophenotypic characteristics and differential diagnosis of primary breast carcinomas with signet ring cell differentiation, as well as differences in the traits of signet ring-like cell mucin. METHODS: A total of five cases of primary breast cancer diagnosed with signet ring cell differentiation and treated at The First People's Hospital of Jingmen from January 2016 to December 2021 were collected. HE, immunohistochemical staining, and AB-PAS staining were used for the analysis. RESULTS: Although we strictly selected all the primary breast cancer cases with signet ring cell differentiation, there were differences in the arrangement of the cells and the grading of nuclei. Our immunohistochemical results showed that the ER was consistently strongly positive, and the PR expression was not consistent, while all the cases of HER2 were negative. CK7 was negative in one case, and CK20 and CK5/6 were not expressed in all the cases. The mucin MUC1 was positive and showed two patterns. MUC2 was strongly positive in all the cases. All the cases were negative for CDX2, SATB2, PAX8, TTF-1, and Napsin A, while the positive expression of COX2, Villin, and WT-1 was not constant. One case expressed neuroendocrine markers. The expression level of Ki67 was between 10 and 30%. AB (pH 2.5)-PAS staining revealed that the intracellular mucus contained more cells with neutral mucus, while the extracellular mucus was mainly acidic. CONCLUSION: We found that histological morphology, cell morphology, and nuclear grading differentiate among different cases. The immunohistochemical characteristics of primary breast cancers diagnosed with signet ring cell differentiation are helpful for identification. The differences in the expression patterns of mucins may be related to unfavorable clinicopathological factors, but their usefulness as a prognostic marker remains to be further understood. The heterogeneity of cell mucus, the differentiation of tumor cells, and the phenotypic changes of tumors also need further study.

Percutaneous Full Endoscopic Lumbar Discectomy for Symptomatic Adjacent Segment Disease after Lumbar Fusion in Elderly Patients.

PURPOSE: Treatment of adjacent segment disease (ASD) is still controversial. The aim of this study was to evaluate the short-term efficacy and safety and to analyze the technical advantages, surgical approach, and indications of percutaneous full endoscopic lumbar discectomy (PELD) in the treatment of ASD after lumbar fusion in elderly patients. METHODS: A retrospective of 32 patients with symptomatic ASD were accepted for PELD from October 2017 to January 2020. All patients used the transforaminal approach and recorded the operation time and intraoperative conditions. Preoperative, 3, 12, 24 months of postoperative and at the last follow-up, the pain of back and leg of visual analog scale (VAS), Oswestry dysfunction index (ODI), and Japanese Orthopaedic Association Assessment Treatment Score (JOA) were performed, and the paired student's t test was used to the compare the continuous variables preoperatively and postoperatively. The clinical efficacy was evaluated according to MacNab standards. The lumbar MRI was performed to evaluate the decompression of the nerve roots, and the lumbar lateral and dynamic X-rays were performed to evaluate the stability of the surgical segment. RESULTS: A total of 32 patients were included in the study, including 17 males and 15 females. The follow-up time ranged from 24 to 50 months, with an average of (33.2 ± 8.1) months and an average operation time of (62.7 ± 28.1) minutes. Compared to preoperatively, the VAS score of the back and leg pain (p < 0.05), ODI (p < 0.05), and JOA (p < 0.05) postoperatively were significantly improved. At the last follow-up, according to the modified MacNab standard assessment, 24 cases were excellent, five cases were good, and three cases were fair, the excellent and good rate was 90.65%. As for complications, one case had a small rupture of the dural sac during the operation, which was found but not repaired during the operation, and one case recurred after the operation. At the last follow-up, there were three cases of intervertebral instability. CONCLUSION: PELD showed satisfactory short-term efficacy and safety in the management of ASD after lumbar fusion in elderly patients. Therefore, PELD might be an alternative choice for elderly patients with symptomatic ASD after lumbar fusion, but surgical indications must be strictly controlled.

The activation mechanism and antibody binding mode for orphan GPR20.

GPR20 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for gastrointestinal stromal tumors (GIST) owing to its differentially high expression. An antibody-drug conjugate (ADC) containing a GPR20-binding antibody (Ab046) was recently developed in clinical trials for GIST treatment. GPR20 constitutively activates Gi proteins in the absence of any known ligand, but it remains obscure how this high basal activity is achieved. Here we report three cryo-EM structures of human GPR20 complexes including Gi-coupled GPR20 in the absence or presence of the Fab fragment of Ab046 and Gi-free GPR20. Remarkably, the structures demonstrate a uniquely folded N-terminal helix capping onto the transmembrane domain and our mutagenesis study suggests a key role of this cap region in stimulating the basal activity of GPR20. We also uncover the molecular interactions between GPR20 and Ab046, which may enable the design of tool antibodies with enhanced affinity or new functionality for GPR20. Furthermore, we report the orthosteric pocket occupied by an unassigned density which might be essential for exploring opportunities for deorphanization.

Comparison of Oblique Lumbar Interbody Fusion Combined with Posterior Decompression (OLIF-PD) and Posterior Lumbar Interbody Fusion (PLIF) in the Treatment of Adjacent Segmental Disease(ASD).

BACKGROUND: An unintended consequence following lumbar fusion is the development of adjacent segment disease (ASD). Oblique lumbar interbody fusion combined with posterior decompression (OLIF-PD) is another feasible option for ASD, and there is no literature report on this combined surgical strategy. METHODS: A retrospective analysis was performed on 18 ASD patients requiring direct decompression in our hospital between September 2017 and January 2022. Among them, eight patients underwent OLIF-PD revision and ten underwent PLIF revision. There were no significant differences in the baseline data between the two groups. The clinical outcomes and complications were compared between the two groups. RESULTS: The operation time, operative blood loss and postoperative hospital stay in the OLIF-PD group were significantly lower than those in the PLIF group. The VAS of low back pain in the OLIF-PD group was significantly better than that in the PLIF group during the postoperative follow-up. The ODI at the last follow-up in the OLIF-PD group and the PLIF group were significantly relieved compared with those before operation. The excellent and good rate of the modified MacNab standard at the last follow-up was 87.5% in the OLIF-PD group and 70% in the PLIF group. There was a statistically significant difference in the incidence of complications between the two groups. CONCLUSION: For ASD requiring direct decompression after posterior lumbar fusion, compared with traditional PLIF revision surgery, OLIF-PD has a similar clinical effect, but has a reduced operation time, blood loss, hospital stay and complications. OLIF-PD may be an alternative revision strategy for ASD.

Analysis of the curative effect of cervical spondylotic radiculopathy with osseous foraminal stenosis using ultrasonic osteotome in anterior cervical surgery.

PURPOSE: To explore the clinical efficacy and operation points of cervical radiculopathy with osseous foraminal stenosis treated with ultrasonic osteotome in anterior cervical surgery. METHODS: From January 2018 to June 2021，a retrospective analysis of 23 patients with cervical radiculopathy with bony foraminal stenosis during this period was retrospectively analyzed. Anterior Cervical Discectomy and Fusion (ACDF) was used for all cases in this group. Intraoperative use of ultrasonic osteotome to decompress the nerve in the intervertebral foramina. The operation time, intraoperative blood loss and complication rate were recorded in this group of patients. Interbody fusion was evaluated using Brantigan criteria. The IC-PACS imaging system was used to measure the intervertebral foramen area (IFA) before and after surgery to evaluate the range of decompression. The VAS (Visual Analogue Scale, VAS) score and NDI (Neck Disability Index, NDI) score before and after surgery were recorded to evaluate the clinical efficacy. RESULTS: All enrolled patients were followed up regularly for 1 year or more. The mean operative time was 61.5 ± 8.0 minutes. The average intraoperative blood loss was 88.3 ± 12.8 ml, and the average hospital stay was 8.1 ± 1.7d. Twenty one cases of successful fusion were followed up 1 year after operation, and the fusion rate was 91.3%. IFA expanded from 25.1 ± 4.0 mm2 before operation to 57.9 ± 3.4 mm2 at 1 year after operation, and the difference was statistically significant (P < 0.001). The VAS score and NDI score of patients 3 days after surgery, 3 months after surgery, and 1 year after surgery were significantly lower than those before surgery (P < 0.001). There was 1 case of dysphagia and 1 case of Cage subsidence after operation, and the complication rate was 8.6%. CONCLUSION: Anterior cervical surgery using ultrasonic osteotome in the treatment of cervical radiculopathy with bony foraminal stenosis has reliable clinical efficacy and high safety, and is worthy of clinical promotion.

Structural insight into the constitutive activity of human orphan receptor GPR12.

G protein-coupled receptor 12 (GPR12) is an orphan G protein-coupled receptor that is highly expressed in the thalamus of the brain and plays a vital role in driving thalamocortical functions in short-term memory. GPR12 performs high constitutive activity and couples with Gs, increasing the intracellular cyclic adenosine monophosphate (cAMP) level when it is expressed. However, exploitation for drug development is limited since it is unclear how GPR12 initiates self-activation and signal transduction, and whether it can be modulated by endogenous or synthetic ligands. Here, we report the cryo-electron microscopy structure of the GPR12-Gs complex in the absence of agonists. Our structure reveals the key determinants for the intrinsically high basal activity of GPR12, including extracellular loop 2 partially occupying the orthosteric binding pocket, a tight-packed TM1 and TM7, and unique activation-related residues in TM6 and TM7. Together with mutagenesis data, this study will improve our understanding of the function and self-activation of the orphan receptor GPR12, enable the identification of endogenous ligands, and guide drug discovery efforts that target GPR12.

Clinical effect of channel assisted cervical key hole technology combined with ultrasonic bone osteotome in the treatment of single segment cervical spondylotic radiculopathy.

Objective: To explore the clinical effect and operating skills of channel assisted Cervical Key Hole technology combined with Ultrasonic Bone Osteotome (CKH-UBO) in the treatment of single segment cervical spondylotic radiculopathy (CSR). Methods: From June 2018 to June 2020, 14 patients diagnosed with CSR and treated with channel assisted CKH-UBO were collected. The duration of the disease, the length of the incision, the operation time, the amount of bleeding during the operation, the length of hospitalization and the complications were recorded. The Range Of Motion (ROM) and the stability of the surgical segment were recorded before and after the operation. Visual analog scale (VAS), neck disability index (NDI) and modified macnab efficacy evaluation criteria were used to evaluate the surgical efficacy. Results: The operative segments of the enrolled patients were all lower cervical vertebrae. The average incision length was 2.0 ± 0.1 cm, the operation time was 42.2 ± 5.7 min, the intraoperative bleeding volume was 32.7 ± 4.1 ml, and the hospital stay was 5.6 ± 1.2 days. There was no difference in ROM between preoperative and 3 months and 1 year after operation (P > 0.05), and all patients did not have segmental instability. The VAS scores of neck pain before surgery, 3 days after surgery, 3 months after surgery, and 1 year after surgery were 5.6 ± 1.2, 1.6 ± 0.6, 1.1 ± 0.7, 0.6 ± 0.5, and the VAS scores of upper limb pain were 6.2 ± 1.2, 1.7 ± 0.7, 1.1 ± 0.6, 0.6 ± 0.5. The NDI scores of upper limb pain before surgery, 3 days after surgery, 3 months after surgery, and 1 year after surgery were 36.7 ± 3.5, 9.8 ± 2.4, and 3.9 ± 1.5, 1.8 ± 1.0, The VAS and NDI scores at all follow-up time points after operation were significantly lower than those before operation (P < 0.001). One year after operation, the curative effect was evaluated according to the modified macnab evaluation standard, and the excellent and good rate was 100%. The complication rate was 6.25%. Conclusion: Channel assisted CKH-UBO for single segment CSR has the advantages of short operation time, reliable clinical effect, high safety and low complication rate, which is worthy of clinical promotion.

Protective effects of Dendrobium huoshanense polysaccharide on D-gal induced PC12 cells and aging mice, in vitro and in vivo studies.

Dendrobium huoshanense C. Z. Tang et S. J. Cheng polysaccharide (DHP) is the essential active ingredient of D.huoshanense and has high medicinal value. A high dose of D-galactose (D-gal) is commonly utilized in the aging model establishment. In this study, we explored whether DHP shields PC12 cells and aging mice from D-gal caused damage and the possible mechanism. In vitro experiments, D-gal induced PC12 cells were used to investigate, and then DHP was used for treatment. In vivo experiments, 72 SPF ICR male mice were randomly divided into six groups (control: normal saline; model: D-gal (400 mg/kg); VE group: VE (50 µg/ml); DHP groups: D-gal + DHP (15.6 mg/ml; 31.2 mg/ml; 62.4 mg/ml)). The results showed that DHP could enhance the viability of D-gal injured PC12 cells and prevent cell apoptosis. DHP effectively promoted the transition from phase G0/G1 to phase S and inhibited cell cycle arrest. DHP has a potential neuroprotective effect on D-gal caused cognitive and memory disorders in mice. On the one hand, DHP protects the antioxidant enzymes SOD, GSH-PX, and CAT from excessive ROS buildup. On the other hand, DHP was demonstrated to block the expression of the P53/P21 signaling pathway-related proteins P53, P21, and P16. These results imply that DHP could be a potential neuroprotective agent against aging. PRACTICAL APPLICATIONS: Cognitive and memory decline caused by aging problems has become a problem in recent years. There are many theories about aging, among which oxidative stress is considered to be one of the important pathophysiological parts of various diseases in the aging process. In this study, DHP could not only improve the damage of D-Gal to PC12 cells, but also improve the cognitive and memory impairment caused by D-Gal in mice. In conclusion, this study verified the anti-aging effect of DHP from in vitro and in vivo experiments, and its mechanism may involve the P53/P21 pathway. Therefore, this study indicated that polysaccharides from Dendrobium huoshanense, a traditional Chinese medicine of homologous medicine and food, had potential and industrial value as potential anti-aging drugs.

Cadmium perturbed lipid profile and induced liver dysfunction in mice through phosphatidylcholine remodeling and promoting arachidonic acid synthesis and metabolism.

Cadmium ion (Cd2+) exposure has been reported to associate with the prevalence of dyslipidemia, and contribute to the initiation and progression of nonalcoholic fatty liver disease (NAFLD). However, Cd2+ exposure perturbed specific metabolic pathways and underlying mechanisms are still unclear. In the present study, through lipidomics analyses of differential metabolites in serum between the Cd2+-exposed mice and the control group, 179 differential metabolites were identified, among which phosphatidylcholines (PCs) accounted for 49 % metabolites. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment assay indicates that PCs participate in the metabolic pathways, including the Arachidonic Acid (AA) metabolism, which also could be potential NAFLD biomarkers. Moreover, in vivo and in vitro results suggested that Cd2+ exposure induced PC synthesis and remodeling, and increased AA level by promoting fatty acid desaturase 1 (FADS1) to catalyze synthesis process instead of cytosolic phospholipase A2 (cPLA2) mediated release pathway. Inhibition of FADS1 by T3364366 could reverse Cd-induced AA, prostaglandin E2 (PGE2) and triglyceride (TAG) levels, and it also reduce cisplatin resistance in HepG2 cells. This study provides new evidence of Cd2+-induced dyslipidemia and reveals underlying molecular mechanism involved in liver dysfunction of Cd2+ exposure.

Analysis of curative effect of percutaneous coaxial large channel endoscopic lumbar interbody fusion in the treatment of degenerative lumbar spinal stenosis.

Objective: To investigate the clinical efficacy and technical points of Percutaneous Coaxial Large-channel Endoscopic Lumbar Interbody Fusion (PCLE-LIF) in the treatment of degenerative lumbar spinal stenosis. Methods: The clinical data of patients with single-segment degenerative lumbar spinal stenosis who underwent PCLE-LIF surgery from January 2019 to June 2021 were retrospectively analyzed. Surgery-related data included symptom duration, operation time, hospital stay, and complication rate. Functional score data included low back pain and lower extremity pain VAS score, ODI score, and MacNab criteria were used to evaluate clinical effects. The Brantigan criteria were used to evaluate the interbody fusion. Results: There were 62 patients in this group, including 35 males and 27 females. The surgical sites were all lower lumbar spine, including 35 cases of lumbar L4/5 and 27 cases of L5/S1. The length of hospital stay was 7.7 ± 1.4 days. All patients were followed up regularly for 1 year. The interbody fusion rate was 93.5% at 1 year after operation. There were 2 cases of numbness, 2 cases of nerve edema and pain, 1 case of cage displacement, and 1 case of pedicle screw loosening. The complication rate was 9.6%. The VAS scores of low back pain 1 day before surgery, 3 days, 3 months and 1 year after surgery were 4.48 ± 1.06, 0.84 ± 0.81, 0.40 ± 0.56, 0.39 ± 0.69, and the VAS of lower extremity pain at each time point of appeal were 5.58 ± 0.98, 0.91 ± 0.58, 0.31 ± 0.46, 0.19 ± 0.40. The ODI scores at 1 day before surgery, 3 months and 1 year after surgery were 60.01 ± 6.21, 15.58 ± 2.84, 8.82 ± 2.15. The ODI scores and VAS scores of low back pain and lower extremity pain at each follow-up time point after operation were significantly lower than those before operation (p < 0.05). The 1-year follow-up after operation was evaluated by the modified MacNab standard, and the results were excellent in 36 cases, good in 23 cases, fair in 3 cases, and poor in 0 cases, with an excellent and good rate of 95.2%. Conclusion: Percutaneous coaxial large-channel endoscopic lumbar interbody fusion in the treatment of degenerative lumbar spinal stenosis has good short-term efficacy and high safety, and is worthy of popularization.

Soluble Protein Hydrolysate Ameliorates Gastrointestinal Inflammation and Injury in 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Mice.

Inflammatory bowel diseases (IBD) are chronic, recurring gastrointestinal diseases that severely impair health and quality of life. Although therapeutic options have significantly expanded in recent years, there is no effective therapy for a complete and permanent cure for IBD. Well tolerated dietary interventions to improve gastrointestinal health in IBD would be a welcome advance especially with anticipated favorable tolerability and affordability. Soluble protein hydrolysate (SPH) is produced by the enzymatic hydrolysis of commercial food industry salmon offcuts (consisting of the head, backbone and skin) and contains a multitude of bioactive peptides including those with anti-oxidant properties. This study aimed to investigate whether SPH ameliorates gastrointestinal injury in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Mice were randomly assigned to four groups: Control (no colitis), Colitis, Colitis/CP (with control peptide treatment), and Colitis/SPH (with SPH treatment). Colitis was induced by cutaneous sensitization with 1% TNBS on day -8 followed by 2.5% TNBS enema challenge on day 0. Control peptides and SPH were provided to the mice in the Colitis/CP or Colitis/SPH group respectively by drinking water at the final concentration of 2% w/v daily from day -10 to day 4. Then, the colon was harvested on day 4 and examined macro- and microscopically. Relevant measures included disease activity index (DAI), colon histology injury, immune cells infiltration, pro- and anti-inflammatory cytokines and anti-oxidative gene expression. It was found that SPH treatment decreased the DAI score and colon tissue injury when compared to the colitis-only and CP groups. The protective mechanisms of SPH were associated with reduced infiltration of CD4+ T, CD8+ T and B220+ B lymphocytes but not macrophages, downregulated pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-6), and upregulated anti-inflammatory cytokines (transforming growth factor-ß1 and interleukin-10) in the colon tissue. Moreover, the upregulation of anti-oxidative genes, including ferritin heavy chain 1, heme oxygenase 1, NAD(P)H quinone oxidoreductase 1, and superoxide dismutase 1, in the colons of colitis/SPH group was observed compared with the control peptide treatment group. In conclusion, the protective mechanism of SPH is associated with anti-inflammatory and anti-oxidative effects as demonstrated herein in an established mice model of colitis. Clinical studies with SPH as a potential functional food for the prevention or as an adjuvant therapy in IBD may add an effective and targeted diet-based approach to IBD management in the future.

Is liquid biopsy mature enough for the diagnosis of Alzheimer's disease?

The preclinical diagnosis and clinical practice for Alzheimer's disease (AD) based on liquid biopsy have made great progress in recent years. As liquid biopsy is a fast, low-cost, and easy way to get the phase of AD, continual efforts from intense multidisciplinary studies have been made to move the research tools to routine clinical diagnostics. On one hand, technological breakthroughs have brought new detection methods to the outputs of liquid biopsy to stratify AD cases, resulting in higher accuracy and efficiency of diagnosis. On the other hand, diversiform biofluid biomarkers derived from cerebrospinal fluid (CSF), blood, urine, Saliva, and exosome were screened out and biologically verified. As a result, more detailed knowledge about the molecular pathogenesis of AD was discovered and elucidated. However, to date, how to weigh the reports derived from liquid biopsy for preclinical AD diagnosis is an ongoing question. In this review, we briefly introduce liquid biopsy and the role it plays in research and clinical practice. Then, we summarize the established fluid-based assays of the current state for AD diagnostic such as ELISA, single-molecule array (Simoa), Immunoprecipitation-Mass Spectrometry (IP-MS), liquid chromatography-MS, immunomagnetic reduction (IMR), multimer detection system (MDS). In addition, we give an updated list of fluid biomarkers in the AD research field. Lastly, the current outstanding challenges and the feasibility to use a stand-alone biomarker in the joint diagnostic strategy are discussed.

[Comparison of effectiveness between percutaneous coaxial large-channel endoscopic lumbar interbody fusion and minimal invasive transforaminal lumbar interbody fusion in treatment of degenerative lumbar spinal stenosis].

Objective: To compare the effectiveness of percutaneous coaxial large-channel endoscopic lumbar interbody fusion (PE-LIF) and minimal invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of degenerative lumbar spinal stenosis. Methods: The clinical data of 134 patients with single-segment degenerative lumbar spinal stenosis who met the selection criteria between January 2019 and January 2021 were retrospectively analyzed, including 52 cases in PE-LIF group and 82 cases in MIS-TLIF group. There was no significant difference in general data such as gender, age, disease duration, surgical segment, and preoperative visual analogue scale (VAS) scores of low back pain and lower extremity pain, and Oswestry disability index (ODI) between the two groups ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage, hospitalization stay, and complications were recorded and compared between the two groups. The level of serum creatine kinase (CK) was recorded at 1 day before operation and at 1 and 3 days after operation to evaluate intraoperative muscle damage. The Brantigan criteria was used to evaluate the interbody fusion in the two groups. The VAS scores of low back pain and lower extremity pain at 1 day before operation and at 3 days, 3 months, and 1 year after operation, and the ODI scores at 1 day before operation and at 3 months and 1 year after operation were recorded and compared between the two groups. Results: There was no significant difference in operation time and hospitalization stay between the two groups ( P>0.05). The intraoperative blood loss and postoperative drainage in the PE-LIF group were significantly lower than those in the MIS-TLIF group ( P<0.05). There was no significant difference in serum CK between the two groups before operation ( P>0.05), and the serum CK in the PE-LIF group at 1 and 3 days after operation were significantly lower than those in the MIS-TLIF group ( P<0.05). All patients were followed up regularly for 1 year. The postoperative VAS scores of low back pain and lower extremity pain and ODI score in both groups were significantly lower than those before operation ( P<0.05); there was no significant difference between the two groups ( P>0.05). At 1 year after operation, 48 patients in PE-LIF group had successful interbody fusion, and 77 patients in MIS-TLIF group had successful interbody fusion. There was no significant difference in the interbody fusion distribution between the two groups at 3 months and 1 year after operation ( P>0.05). There were 2 and 3 cases of lower limb numbness, 1 and 3 cases of neuroedema pain, 1 and 1 case of Cage displacement, 1 and 1 case of pedicle screw loosening in the PE-LIF group and MIS-TLIF group, respectively. No infection or dural sac tearing occurred in the two groups. There was no significant difference in the incidence of complications between the two groups (9.6% vs. 9.8%) ( χ 2=0.001, P=0.979). Conclusion: In the treatment of single-segment degenerative lumbar spinal stenosis, PE-LIF can achieve similar effectiveness as MIS-TLIF, and PE-LIF has less intraoperative blood loss and less muscle damage.

Application of Ultrasonic Bone Osteotome in Anterior Cervical Disc Resection and Fusion Surgery.

OBJECTIVE: To investigate the application skills and importance of ultrasonic bone osteotome in anterior cervical discectomy and fusion surgery. METHODS: Between January 2018 and December 2020, the data of 97 patients who underwent anterior cervical disc resection and fusion (ACDF) in our hospital were collected and retrospectively analyzed. According to the main instruments for decompression of the intervertebral space, we divided the 97 patients into ultrasonic bone osteotome (UBS) group and traditional high-speed drill (HSD) group. The intraoperative indexes selected for comparison between the 2 groups were intervertebral space decompression time, intraoperative blood loss, incidence and types of complications within the 2 groups of patients, Japanese Orthopedic Association (JOA) scores, and JOA improvement rates of the 2 groups of patients before and after surgery. RESULTS: There was no statistical difference in general data such as age, sex, duration of symptoms, and surgical segment between the 2 groups (P > 0.05). Intervertebral decompression time, intraoperative blood loss, and complications in the UBS group were less than those in the HSD group (P < 0.05). The JOA scores of the 2 groups of patients were significantly improved after the operation compared with scores from before the operation, with results being statistically significant (P < 0.05), however, there was no difference in clinical effect between the 2 groups at each follow-up time point (P > 0.05). CONCLUSIONS: This study shows that in ACDF surgery, UBS is more efficient than HSD and can effectively shorten the operation time and reduce the amount of bleeding and the incidence of complications.