Advances in regional nodal management of early-stage breast cancer

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy:Familial aggregation of obesity

BACKGROUND Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy(SG)between patients with familial aggregation of obesity(FAO)and patients with sporadic obesity(SO)have not been elucidated.AIM To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO.METHODS A total of 193 patients with obesity who underwent SG were selected.Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity(1 SO vs 1FAO,2SO vs 2FAO).The baseline characteristics,weight loss outcomes,prevalence of obesity-related comorbidities and incidence of major surgeryrelated complications were compared between groups.RESULTS We defined FAO as the presence of two or more first-degree relatives with obesity.Patients with FAO did not initially show significant differences in baseline data,short-term postoperative weight loss,or obesity-related comorbidities when compared to patients with SO preoperatively.However,distinctions between the two groups became evident at the two-year mark,with statistically significant differences in both percentage of total weight loss(P=0.006)and percentage of excess weight loss(P<0.001).The FAO group exhibited weaker remission of type 2 diabetes mellitus(T2DM)(P=0.031),hyperlipidemia(P=0.012),and non-alcoholic fatty liver disease(NAFLD)(P=0.003)as well as a lower incidence of acid reflux(P=0.038).CONCLUSION FAO patients is associated with decreased mid-to-long-term weight loss outcomes;the alleviation of T2DM,hyperlipidemia and NAFLD;and decreased incidence of acid reflux postoperatively.

Identification of novel mammalian viruses in tree shrews(Tupaia belangeri chinensis)

The Chinese tree shrew(Tupaia belangeri chinensis),a member of the mammalian order Scandentia,exhibits considerable similarities with primates,including humans,in aspects of its nervous,immune,and metabolic systems.These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer,infectious diseases,metabolic disorders,and mental health conditions.Herein,we used metatranscriptomic sequencing to analyze plasma,as well as oral and anal swab samples,from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses.In total,eight mammalian viruses with complete genomes were identified,belonging to six viral families,including Flaviviridae,Hepeviridae,Parvovirinae,Picornaviridae,Sedoreoviridae,and Spinareoviridae.Notably,the presence of rotavirus was recorded in tree shrews for the first time.Three viruses-hepacivirus 1,parvovirus,and picornavirus-exhibited low genetic similarity(<70%)with previously reported viruses at the whole-genome scale,indicating novelty.Conversely,three other viruses-hepacivirus 2,hepatovirus A and hepevirus-exhibited high similarity(>94%)to known viral strains.Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants.These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews,highlighting the necessity for further research into their potential for crossspecies transmission.

Polymorphism of CYPIAl and GSTMl genes associated with susceptibility of gastric cancer in Shandong Province of China

AIM: To explore whether polymorphisms of the CYPIA1 and GSTM1 genes are associated with susceptibility of stomach cancer.METHODS: A total of 102 stomach cancer cases and 62 healthy persons were diagnosed by pathology in 1998-2000 in the Qilu Hospital of Shandong University. Gene polymorphisms were detected by the PCR using sequence-specific primers. Data analysis of the case-control study was carried out using the unconditional logistic method.RESULTS: After adjustment for age, sex, educational levels, and occupation, the risk factors for stomach cancer were shown to be smoking, Helicobacter pylori(H pylori),and presence of the CYPIM G/G and GSTM1 O/O genotypes.Interaction was observed between the combined genotypes of either CYPIA1 G/G and GSTM1 O/O or H pylori infection,or GSTM1 O/O and H pylori infection or smoking.CONCLUSION: Polymorphisms of the CYPIA1 and GSTM1 genes, H pylori infection and smoking are related to susceptibility to stomach cancer.

Optimization of regional nodal irradiation in the era of sentinel lymph node biopsy

Historically,axillary lymph node dissection(ALND)was the standard management for axillary sentinel lymph node(SLN)-positive patients,because it enables full assessment of overall axillary lymph node(ALN)metastasis status and favorable local-regional control1,2.

THE PREDICTION OF CANCER MORTALITY IN SHANDONG PROVINCE (1991-2000) AND CANCER CONTROL STRATEGY

Shandong Province, with a population of 84 million and located in the east coastline of China, is rich in natural resources and ranks middle in economic develpment of the whole nation. Around 90000 people are dead of cancer each year. In the recent twenty years, trends in malignant neoplasm

Epithelioid trophoblastic tumor of the lower uterine segment and cervical canal:A case report

BACKGROUND Epithelioid trophoblastic tumor(ETT) is the rarest type of gestational trophoblastic tumor(GTT). It has been reported that more than 50% of ETTs arise in the uterine cervix or the lower uterine segment. Here, we report a case of ETT within the lower uterine segment and cervical canal and discuss its manifestations,possible causes, and related influencing factors.CASE SUMMARY A 35-year-old woman(gravida 7, miscarriage 3, induction 2 with 1 being twins,para 2 of cesarean section, live 2), who had amenorrhea for 9 mo after breastfeeding for 22 mo after the last cesarean section, was diagnosed with ETT. The lesion was present in the lower uterine segment and endocervical canal with severe involvement of the anterior wall of the lower uterine segment and the front wall of the lower uterine segment where the cesarean incisions were made.Laboratory tests showed slight elevation of serum beta-human chorionic gonadotropin. Intraoperative exploration showed the presence of a normal-sized uterus body with an enlarged tumor in the lower uterine segment. The surface of the lower uterine segment was light blue, the entire lesion was approximately about 8cm × 8 cm × 9 cm, with compression and displacement of the surrounding tissue.Histological examination diagnosed ETT. Immunohistochemical analysis showed positive expression of p63, with a Ki-67 proliferation index of 40%.CONCLUSION A search of the PubMed database using the search terms "cesarean section" and "epithelioid trophoblastic tumor" retrieved nine articles, including 13 cases of ETT and ETT-related lesions, all 13 cases had a history of cesarean section, and the lesions were all located at the cesarean section incision on the anterior wall of the lower uterine segment. The present case is the 14th reported case of ETT after cesarean section. Therefore, we deduced that cesarean section trauma had an important effect on the occurrence of ETT at this site.

Genetic and Phenotypic Variation of Campylobacter jejuni NCTC11168 Caused by flhA Mutation during Laboratory Passage

Objective Campylobacter jejuni NCTC11168 is commonly used as a standard strain for flagellar biosynthesis research.In this report,two distinguished phenotypic isolates(CJ1Z,flhA mutant strain,lawn;CJ2S,flhA complemented strain,normal colony)appeared during laboratory passages for NCTC11168.Methods Phenotypic assessments,including motility plates,transmission electron microscopy,biofilm formation assay,autoagglutination assay,and genome re-sequencing for these two isolates(CJ1Z,flhA mutant strain;CJ2S,flhA complemented strain)were carried out in this study.Results Transmission electron microscopy revealed that the flagellum was lost in CJ1Z.Phenotypic assessments and genome sequencing of the two isolates were performed in this study.The capacity for biofilm formation,colony auto-agglutination,and isolate motility was reduced in the mutant CJ1Z.Comparative genomic analysis indicated a unique native nucleotide insertion in flhA(nt,2154)that caused the I719Y and I720Y mutations and early truncation in flhA.Conclusion FlhA has been found to influence the expression of flagella in C.jejuni.To the best of our knowledge,this is the first study to describe the function of the C-terminal of this protein.

Synthesis of dimeric butenolide catalyzed by various inorganic silver catalysts

This article describes a method for synthesizing butyrolactone dimers using various inorganic silver salt catalysts.The method was successfully applied to alkyl 2-(2-bromopropyl)malonate 1,providing the dimeric butyrolactone 2 when catalyzed by different silver salt catalysts.This synthesis method not only simplifies the original synthetic route,but also cleverly combines with natural product analogs,providing a strategy for the development of natural product polymer analogs in the future.

A machine learning model to predict efficacy of neoadjuvant therapy in breast cancer based on dynamic changes in systemic immunity

Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.

Update of latest data for combined therapy for esophageal cancer using radiotherapy and immunotherapy:A focus on efficacy,safety,and biomarkers

Esophageal cancer usually has a poor prognosis.Given the significant breakthrough with tumor immunotherapy,an increasing number of clinical studies have demonstrated that the combination of radiotherapy and immune checkpoint inhibitors(ICIs)may have a synergistic effect and good outcome in esophageal cancer.Clinical studies of immunoradiotherapy(iRT)for esophageal cancer have proliferated enormously from 2021 to the present.However,a summary of the efficacy and toxicity of combined therapy to guide esophageal cancer treatment in clinical practice is lacking.For this review,we integrate the latest data to analyze and assess the efficacy and safety of iRT for esophageal cancer.In addition,we discuss better predictive biomarkers,therapeutic options for specific populations,and other challenges to identify directions for future research design.

Reabsorption of intervertebral disc prolapse after conservative treatment with traditional Chinese medicine:A case report

BACKGROUND Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation(LIDH)within a few weeks.CASE SUMMARY Computed tomography and magnetic resonance imaging(MRI)of the lumbar region of a 25-yearold male diagnosed with LIDH showed prolapse of the L5/S2 disc.The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge.The patient elected a conservative treatment regimen that included traditional Chinese medicine(TCM),acupuncture,and massage.During a follow-up period of more than 12 mo,good improvement in pain was reported without complications.MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation.CONCLUSION A conservative treatment regimen of TCM,acupuncture,and massage promoted reabsorption of a prolapsed disc.

Lifestyle improvement and the reduced risk of cardiovascular disease:the China-PAR project

BACKGROUND The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease(CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project(Prediction for Atherosclerotic Cardiovascular Disease Risk in China).METHODS A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors(LFs)(smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios(HRs) and corresponding 95% confidence intervals(CIs). The risk advancement periods(RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage(PAR%) were also calculated.RESULTS A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1healthy LFs, maintaining 3–4 healthy LFs was associated with a 40% risk reduction of incident CVD(HR = 0.60, 95% CI: 0.45–0.79)and delayed CVD risk by 6.31 years(RAP:-6.31 [-9.92,-2.70] years). The PAR% of maintaining 3–4 unhealthy LFs was 22.0%compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2to 3–4 was associated with a 23% lower risk of CVD(HR = 0.77, 95% CI: 0.60–0.98).CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Deciphering the potential mechanism of Siwu decoction for treating cancer-related anemia based on network pharmacology and molecular docking technology

Background:Siwu decoction(SWD)is a traditional Chinese herbal decoction commonly used for treating various symptoms of blood deficiency and blood stasis,including cancer-related anemia(CRA).However,due to its complex composition,the key active ingredients and underlying mechanisms of its therapeutic effects often remain unknown.This research aims to use network pharmacology and molecular docking technology to systematically elucidate the potential mechanisms underlying the efficacy of SWD in treating cancer-related anemia.Methods:The key constituents of SWD were procured from the TCMSP database.Leveraging the Swiss ADME and Swiss Target Prediction databases,potential targets were recognized.Disease-related targets were assembled via the GeneCards and DrugBank databases.Constructing the PPI network involved the utilization of the STRING database,followed by visualization through Cytoscape 3.9.1 software.Subsequently,GO and KEGG enrichment analysis was conducted utilizing the DAVID database,with visual analysis performed on the macrobiotic platform.For molecular docking,the Autodock software was employed,and the molecular docking outcomes were visualized using the PyMOL software.Results:In this investigation,a comprehensive revelation of 18 primary active compounds and 511 associated targets linked to CRA was accomplished.The outcomes of protein-protein interaction(PPI)analysis unequivocally identified AKT1,EGFR,SRC,VEGFA,HRAS,MAPK3,and STAT3 as pivotal proteins within the SWD’s framework for effective CRA intervention.Notably,signaling pathways such as the HIF-1,JAK-STAT,TNF-α,and PI3K-Akt pathways,intricately involved in hematopoietic stem cell proliferation,differentiation,and inflammatory response,emerged as closely intertwined with the therapeutic application of SWD for CRA treatment.The congruence between these potential targets and SWD’s primary therapeutic constituents for CRA treatment was substantiated by the outcomes of molecular docking analysis.Conclusion:This work provided a reference for further fundamental research by outlining the primary active ingredients and putative molecular mechanisms of SWD in the treatment of CRA.

Pyrotinib is effective in both trastuzumab-sensitive and primary resistant HER2-positive breast tumors

Objective: Primary resistance to trastuzumab frequently occurs in human epidermal growth factor receptor 2(HER2)-positive(+) breast cancer patients and remains a clinical challenge. Pyrotinib is a novel tyrosine kinase inhibitor that has shown efficacy in the treatment of HER2+ breast cancer. However, the efficacy of pyrotinib in HER2+ breast cancer with primary trastuzumab resistance is unknown.Methods: HER2+ breast cancer cells sensitive or primarily resistant to trastuzumab were treated with trastuzumab, pyrotinib, or the combination. Cell proliferation, migration, invasion, and HER2 downstream signal pathways were analyzed. The effects of pyrotinib plus trastuzumab and pertuzumab plus trastuzumab were compared in breast cancer cells in vitro and a xenograft mouse model with primary resistance to trastuzumab.Results: Pyrotinib had a therapeutic effect on trastuzumab-sensitive HER2+ breast cancer cells by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT) and rat sarcoma virus(RAS)/rapidly accelerated fibrosarcoma(RAF)/mitogen-activated protein kinase(MAPK)/extracellular-signal regulated kinase(ERK)pathways. In primary trastuzumab-resistant cells, pyrotinib inhibited cell growth, migration, invasion, and HER2 downstream pathways, whereas trastuzumab had no effects. The combination with trastuzumab did not show increased effects compared with pyrotinib alone. Compared with pertuzumab plus trastuzumab, pyrotinib plus trastuzumab was more effective in inhibiting cell proliferation and HER2 downstream pathways in breast cancer cells and tumor growth in a trastuzumab-resistant HER2+ breast cancer xenograft model.Conclusions: Pyrotinib-containing treatments exhibited anti-cancer effects in HER2+ breast cancer cells sensitive and with primary resistance to trastuzumab. Notably, pyrotinib plus trastuzumab was more effective than trastuzumab plus pertuzumab in inhibiting tumor growth and HER2 downstream pathways in HER2+ breast cancer with primary resistance to trastuzumab. These findings support clinical testing of the therapeutic efficacy of dual anti-HER2 treatment combining an intracellular small molecule with an extracellular antibody.

Molecular Epidemiological Study of a Human Brucellosis Outbreak—Weihai City,Shandong Province,China,2022

What is already known about this topic?Brucellosis,mainly caused by Brucella melitensis(B.melitensis),is regarded as a significant zoonotic disease in China.In Weihai,located at the eastern end of the Shandong Peninsula,brucellosis has been in a low epidemic phase for the past five years.What is added by this report?This was the initial report of a brucellosis outbreak in the last five years.Strains of B.melitensis bv.3 from Weihai and other cities showed a close genetic relationship,suggesting a potential common ancestry.What are the implications for public health practice?Epidemiological investigations depend on standardized and effective molecular typing methods and analysis tools for public health laboratories to identify and trace outbreaks.Understanding the circulation patterns of livestock in free-range households in heavily affected areas is essential for controlling the spread of brucellosis.

Polymorphisms of interleukin-10 promoter are not associated with prognosis of advanced gastric cancer

AIM: To evaluate the association between of the interleukin-10 (IL-10) promoter polymorphisms and survival of advanced gastric cancer (GC) patients. METHODS: The IL-10 (-1082, rs1800896; -819, rs1800871; and-592, rs1800896) genotypes in 234 patients with advanced gastric cancer and in 243 healthy controls were determined by polymerase chain reaction-restriction fragment length polymorphism assay. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by unconditional logistic regression for the associations between IL-10 genotypes and the risk of GC. The Kaplan-Meier method with log-rank testing was used to evaluate the association between genotype and survival of the patients.RESULTS: The IL-10 -1082 G allele and GCC (-1082, -819 and -592) haplotype were associated with increased gastric cancer risks (OR 1.2, 95% CI 0.6-3.2, P = 0.007, for -1082 G allele, OR = 2.3, 95% CI, 1.2-4.1, P = 0.005, for GCC haplotype, respectively). However, none of the three IL-10 gene polymorphisms (-1082, -819 and -592) was correlated with gastric cancer survival (P > 0.05), and none of the genotypes of the three IL-10 sites was found as independent prognostic risk factors in the multivariate test. CONCLUSION: IL-10 gene promoter polymorphisms may not be associated with the prognosis of advanced gastric cancer.

Extraordinary response of metastatic pancreatic cancer to apatinib after failed chemotherapy: A case report and literature review

Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer(PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage Ⅳ, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well.

Rapid quantification of hepatitis B virus DNA by real-time PCR using efficient TaqMan probe and extraction of virus DNA

AIM: To rapidly quantify hepatitis B virus (HBV) DNA by real-time PCR using efficient TaqMan probe and extraction methods of virus DNA. METHODS: Three standards were prepared by cloning PCR products which targeted S, C and X region of HBV genome into pGEM-T vector respectively. A pair of primers and matched TaqMan probe were selected by comparing the copy number and the Ct values of HBV serum samples derived from the three different standard curves using certain serum DNA. Then the efficiency of six HBV DNA extraction methods including guanidinium isothiocyanate, proteinase K, NaI, NaOH lysis, alkaline lysis and simple boiling was analyzed in sample A, B and C by real-time PCR. Meanwhile, 8 clinical HBV serum samples were quantified. RESULTS: The copy number of the same HBV serum sample originated from the standard curve of S, C and X regions was 5.7 × 104/mL, 6.3 × 102/mL and 1.6 × 103/ mL respectively. The relative Ct value was 26.6, 31.8 and 29.5 respectively. Therefore, primers and matched probe from S region were chosen for further optimization of six extraction methods. The copy number of HBV serum samples A, B and C was 3.49 × 109/mL, 2.08 × 106/mL and 4.40 × 107/mL respectively, the relative Ct valuewas 19.9, 30 and 26.2 in the method of NaOH lysis, which was the efficientest among six methods. Simple boiling showed a slightly lower efficiency than NaOH lysis. Guanidinium isothiocyanate, proteinase K and NaI displayed that the copy number of HBV serum sample A, B and C was around 105/mL, meanwhile the Ct value was about 30. Alkaline failed to quantify the copy number of three HBV serum samples. Standard deviation (SD) and coefficient variation (CV) were very low in all 8 clinical HBV serum samples, showing that quantification of HBV DNA in triplicate was reliable and accurate. CONCLUSION: Real-time PCR based on optimized primers and TaqMan probe from S region in combination with NaOH lysis is a simple, rapid and accurate method for quantification of HBV serum DNA.

Effects of Fujian tablet on Nogo-A mRNA expression and plasticity of the corticospinal tract in a rat model of focal cerebral ischemia

The present study investigated the effects of Fujian tablet, a Chinese medicine compound that can nourish liver and kidney, on corticospinal tract plasticity and cervical cord microenvironment in rats with focal cerebral ischemia. Results showed that motor function of rats with right proximal middle cerebral artery occlusion was significantly improved following treatment with Fujian tablet, 9 g crude drug/kg. Anterograde tracing revealed significantly increased biotinylated dextran amine expression in the denervated （left） side of the cervical cord （C4-6） following Fujian tablet treatment, and significantly decreased Nogo-A mRNA expression was detected in the denervated side of the cervical cord （C4-6） using in situ hybridization. Pearson＇s correlation analysis showed a negative correlation between biotinylated dextran amine and Nogo-A mRNA expression （r = -0.943, P 〈 0.01）. Results demonstrated that Fujian tablet can promote corticospinal tract plasticity possibly through the inhibitory effect on Nogo-A mRNA expression in the cervical spinal cord, thereby improving motor dysfunction.