Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

Objective:To explore the epileptogenic network patterns in 14 patients with mesial temporal lobe epilepsy (mTLE) originating from the amygdala.Methods:A total of 14 patients with mTLE originating from the amygdala underwent preoperative evaluation in Department of Epilepsy, Guangdong Sanjiu Brain Hospital from January 1, 2019 to December 31, 2023 were selected. A retrospective analysis was performed on the clinical data of these patients. Epileptogenic network patterns were further explored based on stereo-electroencephalogram (SEEG) and positron emission tomography-computed tomography (PET-CT).Results:Craniocerebral MRI indicated 12 patients with unilateral amygdala hypertrophy, and 2 with increased T2-FLAIR signal in the amygdala but no obvious volume change. During interictal period, scalp EEG indicated discharges in one or both temporal regions and distinguished at the lesion side. During ictal period, scalp EEG indicated that the initial side is consistent with the lesion side. Three clinical phenotypes and epileptogenic network patterns were summarized: the first type ( n=5) had clinical manifestations as aura→automotor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→preinsula→temporal pole (by SEEG) and low metabolism in the medial structures of the temporal lobe (by PET-CT); the second type ( n=6) had clinical manifestations as aura→hypermotor/complex motor→autonomic symptoms, with epileptic seizure starting from amygdala→hippocampus→temporal pole→frontal orbital gyrus and anterior cingulate cortex→insula (by SEEG) and low metabolism in the medial structures of the temporal lobe, temporal pole, insula, frontal-orbital gyrus, and inner frontal lobe (by PET-CT); the third type ( n=3) had clinical manifestations as aura→bilateral symmetrical dystonia→autonomic symptoms (with or without oral-alimentary automotor), with epileptic seizure starting from amygdala→hippocampus and insula→temporal pole and adjacent temporal neocortex (by SEEG) and low metabolism in the mesial structures of the temporal lobe and the insula (by PET-CT). Conclusion:The different clinical phenotypes of patients with mTLE originating from the amygdala may have equivalent epileptogenic network patterns.

Objective:To establish a lumbosacral triangle (composed of L 5 transverse process, S 1 superior articular process, sacral ala and iliac crest) classification and to guide L 5S 1 endoscopic surgery. Methods:A total of 647 patients with low back pain who admitted to Tianjin Hospital from January 2016 to October 2018 were retrospectively analyzed, including 315 males and 332 females, aged 42.9±15.1 years (range, 19-74 years). The L 5 transverse process sacral distance (TSD), inter trans-verse process length (ITL), interlaminar width (ILW), interlaminar height (ILH), iliosacral angle (ISA), iliac crest height (IH), intervertebral space height (ISH), intervertebral foramen height (IFH), and intervertebral foramen width (IFW) were measured based on lumbar spine anterior-posterior and lateral radiographs. Spearman correlation analysis and hierarchical cluster analysis were used to establish the lumbosacral triangle classification. A total of 822 patients underwent endoscopic L 5S 1 surgery based on lumbosacral triangle classification guidance and verification in Tianjin Hospital from January 2020 to December 2022, including 421 males and 401 females, aged 45.1±16.7 years (range, 15-79 years). The visual analogue scale (VAS) and Oswestry disability index (ODI) were compared before and after surgery, and the Macnab criteria were used to assess surgical outcomes. Results:Spearman correlation analysis showed positive correlations between IH and ISA ( r=0.75, P<0.001), IFH and IFW ( r=0.60, P<0.001), TSD and IFH ( r=0.53, P<0.001), and TSD and IFW ( r=0.40, P<0.001). There was a negative correlation between TSD and IH ( r=-0.46, P<0.001), TSD and ISA ( r=-0.42, P<0.001), IFW and ISA ( r=-0.41, P<0.001), IFW and IH ( r=-0.50, P<0.001), IFH and IH ( r=-0.42, P<0.001). According to Spearman correlation analysis, hierarchical cluster analysis and receiver operating characteristic curve, lumbosacral angle was divided into three types: Type 1, L5 transverse process overlapped with sacral alar; Type 2, 07 mm. Based on lumbosacral triangle classification, different endoscopic techniques were used at L5S1 in 822 patients, including interlaminar approach single-axis endoscopy, trans-foraminal approach single-axis endoscopy, trans-foraminal fenestration approach mobile microendoscopy and unilateral biportal endoscopy, the VAS and ODI of all the patients decreased than those preoperative in immediate postoperative period, half a year postoperative period and the final follow up, and the difference was statistically significant ( P<0.05). At the last follow-up, the Macnab score was excellent in 278 cases, good in 475 cases, and fair in 69 cases, with an excellent and good rate of 91.6% (753/822). Conclusion:Lumbosacral triangle classification is simple and practical, and can effectively guide L5S1 endoscopic surgery.

Objective:To establish an artificial intelligence-based surgical selection system utilizing deep learning to assist in the decision-making process for lumbar endoscopic surgery.Methods:General data of 1,110 patients who underwent percutaneous transforaminal endoscopic discectomy, 804 patients who underwent percutaneous interlaminar endoscopic discectomy, 923 patients who underwent mobile microendoscopic discectomy and 623 patients who underwent unilateral biportal endoscopic in Tianjin Hospital from January 2018 to June 2023 were included in the study. Clinical outcomes were assessed using the visual analogue scale (VAS) for leg and back pain, the Oswestry disability index (ODI), and MacNab criteria both before surgery and 12 months postoperatively. Using a random number table method, patients were divided into a training dataset (2,768 cases) and a test dataset (692 cases) at a ratio of 4∶1. Patient clinical symptoms, physical signs, and multi-modal imaging data were input into a deep learning model. This model was structured into three main modules: intervertebral disc detection, surgical necessity identification, and surgical recommendation. The final surgical method was determined using a convolutional neural network incorporating U-Net for segmentation and ResNet for classification. The accuracy and recall rates of each module were evaluated using the test dataset.Results:Compared to preoperative values, all patients showed significant improvements at the 12-month postoperative follow-up. For patients who underwent percutaneous transforaminal endoscopic discectomy, percutaneous interlaminar endoscopic discectomy, mobile microendoscopic discectomy, and unilateral biportal endoscopic surgery, the VAS scores for leg pain decreased from 7.69±0.80, 7.82±0.88, 7.62±0.69, and 7.56±1.00 preoperatively to 1.44±1.09, 1.35±0.82, 1.51±1.08, and 1.43±0.91 postoperatively. Similarly, the VAS scores for back pain decreased from 5.73±0.83, 6.17±0.99, 6.11±0.88, and 6.46±0.95 to 0.93±0.75, 1.01±0.67, 1.40±0.72, and 1.27±0.70, respectively. Additionally, the ODI significantly decreased from 39.91%±4.50%, 40.05%±8.05%, 47.08%±9.50%, and 44.43%±4.71% preoperatively to 5.77%±2.22%, 6.05%±2.31%, 8.51%±2.16%, and 9.51%±3.70% postoperatively, with all differences being statistically significant ( P<0.05). The excellent rate according to the MacNab criteria was 93.12% (3,222/3,460). In the deep learning model, the multi-modal data of 2,768 patients were input in the training set for deep learning to form a surgical identification and operation recommendation system, and the preoperative data of 692 patients were input in the test set to compare with the final operation method. In the intervertebral disc location module, the accuracy of location and designation of the five lumbar intervertebral discs was 97.1%(672/692). In the module of intervertebral disc need for surgery, the accuracy was 94.8%(3,280/3,460) and the recall rate was 91.9%(636/692). As for patients, the accuracy rate was 91.9%(636/692). In the operation recommendation module, the accuracy rate of operation recommendation based on intervertebral disc was 89.5%(569/636), and the accuracy rate of surgical recommendation based on patient was 82.2%(569/692). Conclusion:In this study, an artificial intelligent surgical procedures selection system based on deep learning was established, which could effectively integrate relevant data and accurately guide the selection of lumbar endoscopic surgery.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

OBJECTIVE: To explore the clinical and genetic characteristics of a very early-onset inflammatory bowel disease (VEO-IBD) type 28 child with atypical clinical manifestations. METHODS: A VEO-IBD type 28 child with atypical clinical manifestations admitted to the Department of Neonatology, Children's Hospital Affiliated to Shandong University on November 5, 2021 was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples of the child and his parents were collected for high-throughput sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 50-day-old male, had manifested bronchitis, ulcerative stomatitis, eczema and slightly loose stool. High-throughput sequencing revealed that he has harbored compound heterozygous variants of the IL-10RA gene, namely c.299T>G (p.V100G) and c.301C>T (p.R101W), which were inherited from his father and mother, respectively. Bioinformatic analysis showed that both variants have been recorded in the HGMD database, though the c.299T>G variant has not been included in the gnomAD, 1000 Genomes, ExAC and ESP6500 databases, while the c.301C>T variant has a low population frequency. Both variants were predicted to be deleterious by the online software including SIFT, PolyPhen-2 and Mutation Taster. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PS3+PM2_Supporting+PP3). CONCLUSION The c.299T>G and c.301C>T variants of the IL-10RA gene probably underlay the VEO-IBD type 28 in this child. Above finding has expanded the phenotypic spectrum of VEO-IBD type 28 due to variants of the IL-10RA gene and provided a reference for the clinical diagnosis of this disease.
Humans ; Child ; Male ; Computational Biology ; Diarrhea ; Gene Frequency ; Inflammatory Bowel Diseases/genetics* ; Mutation

Objective:To investigate the effect of unilateral biportal endoscopy (UBE) through extraforaminal approach in the treatment of extra canal lumbosacral nerve entrapment.Methods:Seventeen patients with extra canal lumbosacral nerve root entrapment were treated by UBE through extraforaminal approach in Tianjin Hospital from January 2020 to March 2022, including 9 males and 8 females with an average age of 59.2 years (range 45-71 years). All 17 patients had lower limb radiation pain, numbness, and weakness with or without intermittent claudication. MRI imaging examination showed L 4, 5 foramen stenosis with far lateral disc herniation in 2 case, and L 5S 1 foramen stenosis with far lateral disc herniation in 15 cases, and the height of intervertebral space decreased, resulting in the compression of exiting nerve root and ganglion. Among them, far-out syndrome was diagnosed in 7 cases and transitional lumbarsacral vertebrae was found in 12 cases. The incisions were designed 2 cm away form the projection of adjacent pedicles, while incision at S 1 was designed at the inner edge of the iliac bone due to the shielding of the ilium, taking the outer edge of the isthmus at the outer opening of the intervertebral foramen as the target of channels. The ventral and apical part of superior articular process (SAP) was gradually removed with high-speed burr from its outer edge and isthmus, and the occluded sacral ala and the lower edge of transverse process were removed when necessary. The hyperplastic ligament was removed to expose the exiting nerve root. The protruding intervertebral disc was removed at the ventral side of the nerve root. The far-out syndrome was decompressed laterally along the exiting nerve root until it is completely released. The results and stability were evaluated with visual analogue scale (VAS), Oswestry disability index (ODI), Macnab scores and dynamic X-ray film during follow-up. Results:The operation time was 45-85 min, with an average of 60 min. After remove of the SAP tip and enlarge of the intervertebral foramen, the exiting nerve root and disc protrusion were fully exposed, the exiting nerve root was exposed and released laterally until totally release without entrapment in far out syndrome, and the nerve could be decompressed completely. The symptoms were significantly relieved after operation, and imaging examination showed that facet joints were preserved. During follow-up, the pain and function improved continuously. At final follow-up, the improve rate of VAS and ODI were 85.2% and 86.2%, respectively, and the results were excellent in 15 cases and good in 2 case according to Macnab score, and there was no lumbar instability on dynamic lumbar X-ray film.Conclusion:Extra canal lumbosacral nerve entrapment can be treated by UBE through extraforaminal approach, with sufficient exposure, complete decompression and better preservation of lumbar stability.

Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8⁺ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

Objective:To evaluate the value and efficacy of microscope-assisted minimally invasive anterior lumbar discectomy and zero-profile fusion (ALDF) for lumbar degenerative diseases.Methods:Anterior lumbar distractors were designed to maintain the distraction of intervertebral space and expose the posterior edge of the intervertebral space. From June 2018 to December 2020, 41 cases of lumbar degenerative diseases were treated with this operation, including 19 men and 22 women, aged 29-71 years old (average 42.1 years old). All patients had intractable low back pain. Imaging examination showed lumbar disc degeneration with narrow intervertebral space, including disc herniation with Modic changes in 7 cases, spinal stenosis with instability in 16 cases and spondylolisthesis in 18 cases. The involved levels included L 2,3 in 1 case, L 3,4 in 3 cases, L 2-L 4 in 1 case, L 4,5 in 17 cases and L 5S 1 in 19 cases. An incision was taken that was pararectus for L 2-L 4 and transverse for L 4-S 1, with the intervertebral disc exposed via extraperitoneal approach. The intervertebral space was released and distracted after discectomy in intervertebral space, and self-made distractors were used to maintain the space. Under microscope, the herniation, posterior annulus and osteophyte were removed for sufficient decompression, with a suitable self-anchoring cage implanted into the intervertebral space. The visual analogue score (VAS), Oswestry dysfunction index (ODI), intervertebral space height, lordosis angle and spondylolisthesis rate were evaluated. Results:Operations were performed successfully in all the patients. The operation time was 70-120 min with an average of 90 min, and the intraoperative blood loss was 15-70 ml with an average of 30 ml. No severe complication such as nerve or blood vessel injury occurred. The patients were followed up for 12 to 36 months, with an average of 18 months. At the last follow-up, VAS decreased from 6.4±2.3 to 1.1±0.9, and ODI decreased from 44.9%±16.9% to 5.8%±4.7%. Intervertebral space height recovered from 7.2±2.8 mm to 12.1±2.1 mm and lordosis angle recovered from 6.9°±4.8° to 10.1°±4.6°. X-ray showed significant recovery of intervertebral space height, lordosis angle and spondylolisthesis rate, with obvious interbody fusion and no displacement of cage. For 18 patients of spondylolisthesis, the slippage recovered from 16.6%±9.3% to 7.6%±5.3%, with an average improvement of 54.2%.Conclusion:Microscope-assisted minimally invasive ALDF can provide sufficient decompression and zero-profile fusion for lumbar degenerative diseases with satisfactory results during short-term follow-up.

Objective:To evaluate the safety and validity of enriched autologous bone marrow mesenchymal stem cells (BMSCs) and annular suture for repairing defect after lumbar discectomy.Methods:Enrichment of autologous BMSCs: autologous bone marrow blood was collected from 5 patients undergoing lumbar surgery, and nucleated cells were enriched on gelatin sponge particles by selective cell retention technique. From October 2016 to March 2019, 109 patients with lumbar disc herniation underwent discectomy with mobile microendoscopic discectomy technique, including 61 males and 48 females, aged 24-59 years. Discectomy group: 26 cases received simple discectomy. Suture group: 39 cases received annular suture after discectomy. BMSCs+suture group: 44 cases received intradisc transplantation of gelatin sponge particles enriched with autologous BMSCs and annular suture after discectomy. The perioperative conditions were recorded, with visual analogue scale (VAS), Oswestry dysfunction index (ODI), Pfirrmann grade of disc degeneration, disc height and degree of herniationevaluated after operation.Results:In enrichment test with flow cytometry, the enrichment multiple of nucleated cells and target cells was 6.4±0.9 and 4.2±0.6 respectively, and BMSCs grew well in vitro. The operation time was 35-55 mins. 7 cases in the suture group were transferred to the discectomy group and 10 cases in the BMSCs+suture group were transferred to BMSCs group due to unsuccessful suture. There were no significant differences in VAS, ODI, Pfirrmann grade of disc degeneration, disc height and degree of herniation among the groups. There was no significant difference in intraoperative bleeding, postoperative drainage and length of hospital stay. The incision was healed without redness and swelling. 18 patients were followed up for 6 months, and 91 cases were followed up for 1-3 years (25.0±5.6 months). There was no interbody fusion, heterotopic ossification or infection during follow-up. VAS and ODI decreased significantly after operation in all patients. At final follow-up, the VAS improvement rate of BMSCs+suture group (81.7%±7.9%) was higher than discectomy group (73.0%±8.9%), suture group (74.0%±6.9%) and BMSCs group (75.3%±8.4%); the ODI improvement rate of BMSCs+suture group (91.9%±8.8%) was higher than discectomy group (86.2%±8.1%) and suture group (86.4%±5.5%). According to MRI, the Pfirrmann grade of disc increased 0.7 in discectomy group, 0.6 in suture group, while it did not increased significantly in BMSCs+suture group and BMSCs group, and the progress of Pfirrmann grade in BMSCs+suture group and BMSCs group were lighter than discectomy group and suture group.The disc height decreased in each group, the loss rate of disc height in BMSCs+suture group (17.2%±4.3%) was less than discectomy group (29.3%± 6.3%) and suture group (20.6%±5.7%); and suture group was less than discectomy group. The degree of herniation was reduced by more than 50% in all groups, while 1 case in discectomy group had herniation without clinical symptoms.Conclusion:Autologous BMSCs and annulus suture are safe and effective in repairing the defect after lumbar discectomy, which may help to slow down the degeneration of intervertebral disc.