A case of spinal cord abscess caused by Nocardia cyriacigeorgica is reported. The patient is an elderly man with a history of nephritic syndrome who presented with aggravating lower back pain and then gradually developed urinary retention, weakness and numbness in both lower extremities. Operative intervention was performed, and postoperative pathological findings suggested spinal cord abscess formation. Metagenomic next-generation sequencing of the cerebrospinal fluid identified Nocardia cyriacigeorgica as the causative pathogen. Although appropriate antibiotics were prescribed, the patient died 3 months later.

Objective:To report a case of X-linked myopathy with excessive autophagy (XMEA) and review the literature aiming to analyze the clinical manifestations, muscle imaging, muscle pathology and genetic characteristics of the disease.Methods:The medical history, physical and laboratory examination, muscle imaging and pathology, and genetics of a patient with XMEA who was admitted to QiLu Hospital of Shandong University in June 2018 were retrospectively collected. PubMed, CNKI, and Wanfang Data were searched for relevant literature.Results:This patient was a 40-year-old male who complained of hyper creatine kinase and weakness in his lower extremities for 4 years. Since elementary school, his heels could not touch the ground when squatting and his motor performance was inferior to his peers. Abnormal creatine kinase levels (320-1 167 U/L) were identified several times prior to admission. Magnetic resonance imaging of lower extremities revealed symmetrical fat replacement in bilateral lateral femoral muscles, adductor major and medial head of the gastrocnemius. Muscle biopsy showed intrafibrillar autophagic vacuoles with sarcolemmal features as well as membrane attack complex depositing on the vacuolar membrane; genetic analysis confirmed a hemizygous mutation c. *6A>G in VMA21 gene. Searching the literature, it was found that the onset age of XMEA patients varied from newborns to adulthood. Those XMEA patients with childhood or adulthood-onset mostly exhibited muscle weakness and (or) atrophy in the proximal limbs, with slow progression and normal life expectancy, while those with infant onset were prone to multiple system involvement, rapid disease progression, and high risk of death. Conclusions:XMEA is an extremely rare hereditary autophagic vacuolar myopathy. Although the clinical and prognostic manifestations of XMEA patients vary greatly among different age groups, the muscle pathological changes are relatively consistent, and genetic testing is the main diagnostic method for this disease.

Objective:To analyze the clinical phenotypic characteristics, muscle pathology, genetic mutations and related proteins of myofibrillar myopathy 3 caused by mutation in MYOT gene, and to conduct a literature review and summary of this disease. Methods:A retrospective analysis of the clinical phenotypic characteristics, muscle pathology and genetic test results of a patient with myofibrillar myopathy 3 caused by mutation in MYOT gene diagnosed in Qilu Hospital of Shandong University in December 2018 was conducted. Whole exon sequencing was applied to conduct high-throughput screening of pathogenic genes in the patient. After finding candidate pathogenic mutation, Sanger sequencing was applied to verify the mutation sites in the patient and family members. Meanwhile, functional verification was carried out on the mutation sites found in MYOT gene, and the relevant literature was reviewed. Results:The patient was a 47-year-old woman with weakness in her lower limbs for 8 years. Electromyography showed myogenic changes. The muscle pathology suggested that there was deposition of abnormal substances and rimmed vacuoles within some muscle fibers. Gene testing showed that the patient was a carrier of the MYOT gene c.170C>T (p.Thr57Ile) heterozygous mutation, and her son and daughter also carried the same mutation at the same site. The son of the patient had an elevated creatine kinase level and spontaneous potential was occasionally observed on electromyography, while the daughter had no abnormalities. Two younger brothers did not carry the mutation. Protein functional studies suggested that the mutation of MYOT gene c.170C>T mutation can lead to the change of partial spatial structure of myotilin, and the abnormal aggregation of p62 protein and myotilin was involved in the pathogenesis of the disease. Literature review revealed that c.170C>T (p.Thr57Ile) mutation has only been reported in foreign populations. This is the first detailed report on the clinical phenotype, muscle pathology and gene function of MYOT-related myofibrillar myopathy type 3 in China. Conclusions:The clinical manifestations of myofibrillar myopathy type 3 caused by MYOT gene mutation are heterogeneous, mainly manifested as muscle weakness in the distal or proximal extremities. Muscle pathology reveals abnormal protein deposits and rimmed vacuoles within some muscle fibers. Accurate diagnosis of the disease depends on gene detection. The co-localization of p62 protein and myotilin protein provides a new idea for the diagnosis and molecular mechanism research of the disease.

Objective:To investigate the clinical, muscle biopsy and gene mutation characteristics of nemaline myopathy caused by the NEB gene variants.Methods:A retrospective analysis of the clinical manifestations, auxiliary examinations, muscle biopsies and genetic analysis of 3 nemaline myopathy patients carrying NEB gene mutations diagnosed in the Neuromuscular Pathology Laboratory of Qilu Hospital of Shandong University during 2019-2021 was done. And the related literature was reviewed.Results:All of the 3 patients were congenital onset. The onset symptoms of the 3 patients were weakness of bilateral lower limbs. Physical examinations showed high palatine arches and long narrow faces. Electromyography showed myogenic impairment. Muscle biopsies of the 3 patients revealed myodystrophic changes and nemaline bodies. The ATPase staining of patient 1 showed the predominance and grouping of type 1 muscle fibers. Genetic tests revealed patient 1 carried c.21522+3A>G and c.3471dupC (p.N1158Qfs *5) mutations in the NEB gene, patient 2 carried c.21522+3A>G and c.18991_18992delAG (p.Q6332Afs *8) compound heterozygous mutations and patient 3 carried c.21522+3A>G and c.3448A>T (p.K1150 *) compound heterozygous mutations. All the 3 patients carried the c.21522+3A>G mutation in the NEB gene, which had only been reported in Chinese population. The c.3471dupC (p.N1158Qfs *5), c.18991_18992delAG (p.Q6332Afs *8) and c.3448A>T (p.K1150 *) mutations have not been reported yet. According to American College of Medical Genetics and Genomics guideline, c.21522+3A>G, c.3471dupC (p.N1158Qfs *5), c.3448A>T (p.K1150 *) and c.18991_18992delAG (p.Q6332Afs *8) mutations were all rated pathogenic. Conclusions:The onset age and clinical symptoms of nemaline myopathy are heterogeneous. Muscle biopsy and genetic analysis are important for diagnosis of nemaline myopathy. The c.21522+3A>G mutation in the NEB gene may be more common in Chinese population.

Objective To summarize the clinical , pathological and genetic characteristics of three patients with caveolin-3 associated myopathy and review the literatures .Methods The clinical data of three patients with caveolin-3 associated myopathy were investigated .With informed consent , we performed muscle biopsy and genetic analysis of CAV 3 and PTRF genes.Results All the three patients presented with percussion/pressure-induced rapid contraction , percussion-induced muscle mounding and mechanically induced muscle rippling.Besides, case 1 had weakness and atrophy of hand muscles .Case 2, who manifested with muscle hyperexcitability at onset , developed weakness and atrophy of distal part of lower limbs.Case 3 showed normal muscle strength and tone .All of them had myalgia or tenderness .Muscle biopsy revealed mild myogenic changes in two patients and a muscular dystrophic pattern in one . Immunohistochemical staining of caveolin-3 revealed an even deficiency in case 1 and a mosaic deficiency in cases 2 and 3.Gene analysis revealed a missense mutation ( c.80G>A, p.R27Q) in CAV3 gene of case 1. No mutations were identified in cases 2 and 3.Conclusions There is phenotypic variability in patients with caveolin-associated myopathy , including limb-girdle syndrome , rippling muscle disease , distal myopathy , muscle hypertrophy , idiopathic hyperCKemia and cardiomyopathy .Muscle biopsy and caveolin-3 staining should be performed for the above patients with muscle rippling .

Objective To report four patients with secondary α-dystroglycanopathy caused by guanosine diphosphate-mannose pyrophosphorylase-B ( GMPPB ) gene mutations and review the literature aiming to analyze the clinical manifestations , muscle image , molecular pathology and genetic characteristics of the disease.Methods The medical history , physical examination , electromyography and other clinical data of four patients with secondary α-dystroglycanopathy from two families were collected and retrospectively reviewed from 2009 to 2017.Case 1 ( proband of pedigree 1) and case 2 ( proband of pedigree 2) were then further analyzed with muscle imaging , muscle pathology and targeted next generation gene sequencing (NGS).Results Four patients came from two families (three from the same pedigree), two males and two females, with an onset age of 17 -18 years.All four cases presented as limb-girdle muscular dystrophy (LGMD) overlapping with congenital myasthenic syndrome (CMS) characterized by evident proximal limb weakness in early adulthood and fluctuating muscle weakness .They all had delayed motor milestone and did not perform well in physical education since childhood . Serum creatine kinase was elevated markedly (1877-5275 U/L).Myogenic changes on electromyography and marked attenuation on three Hz repetitive nerve stimulation were observed in all patients .Muscle MRI showed prominent involvement of bilateral hamstrings in case 1 and case 2.Muscular dystrophic patterns were demonstrated on muscle biopsies . Targeted NGS revealed two compound heterozygous missense mutations in GMPPB for each case .Case 1 carried c.860G>T (p.R287L)/c851T>C (p.V284L).Case 2 and his two affected sisters (case 3 and case 4) carried c.1097A >G ( p.N366S)/c.589G >T ( p.V197F) .All of these mutations were novel variants and pedigree analysis suggested that the two mutations were from parents .Compared with normal controls, immunohistochemistry and Western blotting showed significantly decreased expression of α-dystroglycan in the muscle tissue from case 1 and case 2.The myasthenic symptoms of all four patients were improved to varying degrees after treatment with pyridostigmine bromide . Conclusions Mutations in GMPPB can lead to dysfunction both in muscle and in neuromuscular transmission causing overlapping between LGMD and CMS phenotypes . Cholinesterase inhibitors can partly improve the symptoms of myasthenia in such patients .

Objective To evaluate the outcomes of the payment reform at public hospitals in Sanming city.Methods Interrupted time series analysis was used to compare changes of the average days of stay,per capita hospitalization expense,outpatient expense per visit,proportion of medical expense and that of drugs during hospitalization at 21 public hospitals at or above county level before and after the DRGs reform.Results Comparisons before and after the reform found the average days of stay at the original momentum,poor control in curbing the proportion of medical expense and that of drugs during hospitalization,adropping followed by rising trend in the outpatient expense per visit,and minimal drop of the abovementioned proportions.Conclusions The rapid growth of outpatient and hospitalization costs at tertiary hospitals may be incurred by unreasonable cost transfer,structural trend of hospitalization expense makeup,and rationality pending scrutiny.

Tripartite-sector reform (a synergistic reform in public health services,medical insurance and medicine production-circulation) in Sanming city was described in the paper which centers on medical insurance.Tapping full potentials of the medical insurance,the city achieved efficient synergy among healthcare,medical insurance and medication systems.This reform has trimmed out inflated drug pricing to some extent for rooms of maneuver of medical service pricing changes,thus curbing excessive growth of medical costs successfully.The authors proposed areas of further improvements including the relationship between achieving such objective as curbing medical expenditure,and advancement of technical/medical service capacity;that between integrative control of medical insurance expenditure and protection of people's health;the equilibrium of interests between medical insurance,healthcare and medication.All these will contribute to the goal of healthy patients flow and a hierarchical medical system.

Objective To investigate the clinical and pathological features of Guillain-Barré syndrome with treatment-related fluctuations (GBS-TRF).Methods Clinical data were obtained from medical records of patients with GBS-TRF during the period 1999 to 2014 in our Hospital.Sural nerve specimens were collected and summarized retrospectively (two cases).Results Eight of 868 cases with GBS had at least one TRF including three chronic hepatitis B patients.The onset of disease was ranged in age from six to 63 years, averaging 34 years.It is more common in men than in women in a ratio of seven to one.Triggering infections occurred in three patients.The initial symptom included weakness of the lower limbs (five cases) and upper extremities (three cases).Sensory symptom was presented in six patients.Five patients had associated respiratory paralysis.None of them had cranial nerve palsy or autonomic dysfunction.The examination of cerebrospinal fluid showed protein and cell separation.Five patients had two attacks, one had three attacks and two had six attacks.The interval between attacks ranged between 14 days and 46 days (mean 23 days).The striking pathologic finding was the presence of sectional selective nerve fiber degeneration (SNFD) with evidence of demyelination.Conclusions Patients with GBS-TRF show similar onset age, preceding infection, cerebrospinal fluid findings, and electrophysiologic characteristics comparing to patients with GBS,while there are more male patients than female patients.SNFD found in sural nerve biopsy reveals ischemic neuropathy, which predicts that injury of arterioles might play an important role in the pathogenesis of GBS-TRF.

Objective To investigate the clinical and pathological features of Guillain-Barré syndrome with treatment-related fluctuations ( GBS-TRF ).Methods Clinical data were obtained from medical records of patients with GBS-TRF during the period 1999 to 2014 in our Hospital.Sural nerve specimens were collected and summarized retrospectively ( two cases ).Results Eight of 868 cases with GBS had at least one TRF including three chronic hepatitis B patients.The onset of disease was ranged in age from six to 63 years, averaging 34 years.It is more common in men than in women in a ratio of seven:one.Triggering infections occurred in three patients.The initial symptom included weakness of the lower limbs ( five cases ) and upper extremities ( three cases ).Sensory symptom was presented in six patients.Five patients had associated respiratory paralysis.None of them had cranial nerve palsy or autonomic dysfunction.Five patients had two attacks , one had three attacks and two had six attacks.The interval between attacks ranged between 14 days and 46 days ( mean 23 days ).The striking pathologic finding was the presence of sectional selective nerve fiber degeneration ( SNFD ) with evidence of demyelination.Conclusions Patients with GBS-TRF shows similar onset age , preceding infection , cerebrospinal fluid findings, and electrophysiologic characteristics comparing to patients with GBS ,while there are more male patients than female patients.SNFD found in sural nerve biopsy reveals ischemic neuropathy , which predicts that injury of arterioles might play an important role in the pathogenesis of GBS -TRF.