AIM: To observe the activity and distribution of astrocytes and glial fibrillary acid protein(GFAP) after middle cerebral artery occlusion (MCAO). METHODS: The rat MCAO model was made by two-kidney, tow clip renovascular hypertensive rat stroke prone(RHRSP). Rats were killed and brain samples were collected at the end of 1,3,6 and 9 weeks after MCAO, respectively. The ultrastructure of astrocytes was determined at broder of infarct (A area); distant of infarct (B area) and opposite of hemisphere (C area) by electron microscope. The number and optical density of GFAP-positive cells were also observed. RESULTS: The astrocyte proliferation distributed in the whole brain after MCAO. The highest numbers of GFAP-positive cells were observed at A area, then B area. The lowest numbers of GFAP positive cells were found in C area. The time course of GFAP-positive cell change was that the highest number was observed at 1 week after MCAO, then decreased by time from 3, 6 weeks to 9 weeks. The optical density of GFAP-positive cells showed the same patterns. CONCLUSION: The correlation between astrocyte proliferation and tissue damage after MCAO can be estimated by GFAP expression. The astrocyte proliferation plays an important role in healing process after MCAO.

Objective:To report the genetic and clinical features of sorbitol dehydrogenase (SORD) gene-related Charcot-Marie-Tooth disease (CMT) in Chinese population.Methods:Fifty-seven undiagnosed sporadic or autosomal recessive (AR) inherited CMT2 families were collected from the Department of Neurology of the Third Xiangya Hospital from 2009 through 2018 .Polymerase chain reaction combined with Sanger sequencing were used to detect the mutations of SORD gene, and the relative clinical features were summarized. Results:The homozygous SORD gene hot spot mutation c.757delG (p. Ala253GlnfsTer27) was detected in four sporadic patients, accounting for about 7% of the total. Two patients with CMT2 phenotype were characterized by progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in both motor and sensory nerves. Two patients with distal hereditary motor neuropathy (dHMN) phenotype exhibited progressive lower limb weakness and atrophy with electromyogram changes of axonal degeneration in motor nerves only. The age of onset was between five and 16 years, and the CMT neuropathy score was 2-9.Conclusions:The homozygous hot spot mutation of SORD gene (c.757delG, p.Ala253GlnfsTer27), and related childhood or adolescence onset, mildly affected CMT2/dHMN phenotypes are firstly reported in Chinese population. SORD gene-related CMT might be the most common subtype of AR-CMT2.

Objective To analyze the electrophysiological characteristics of Charcot-Marie-Tooth (CMT) disease 1A,1X,2A and myelin protein zero (MPZ)-related CMT in Chinese patients.Methods Baseline electrophysiological data from 36 CMT1A patients,78 CMT1X patients,31 CMT2A patients and 10 MPZ-related CMT patients in the Third Xiangya Hospital and Xiangya Hospital of Central South University during 2004-2018 were analyzed.Electrophysiological recordings were taken from the upper limbs (median nerve,ulnar nerve) and lower limbs (tibial nerve,peroneal nerve).Demyelination in different nerve segments was assessed by measurement of distal motor latency,motor nerve conduction velocity (MNCV),sensory nerve conduction velocity and F-wave latency,and calculation of conduction block,terminal latency index (TLI) and modified F ratio (MFR);Axonal degeneration was assessed by measuring compound motor action potential (CMAP) and sensory nerve action potential.The relationship between the gender,age at onset,duration,Overall Neuropathy Limitation Scale (ONLS) score and indexes of peripheral nerve electrophysiology was statistically analyzed.Results The peripheral nerves of CMT1A patients were characterized by uniform demyelination and axonal degeneration.MNCV ((21.39± 6.72) m/s) and CMAP amplitude (2.40 (3.50) mY) of median nerve of CMT1A patients were decreased.The peripheral nerves of CMT1X patients were also characterized by uniform demyelination and axonal degeneration.MNCV (35.20 (6.77) m/s) and CMAP amplitude (2.60 (3.79) mY) of median nerve of CMT1X patients were decreased.CMT2A patients showed axonal degeneration of the peripheral nerves and CMAP amplitude ((4.75 ±2.38) mV) of median nerve of CMT2A patients was decreased.The electrophysiological data in MPZ-related CMT patients demonstrated variability.The TLI and MFR for the median and ulnar nerves in these four subtypes were normal.MNCV (r=0.423,P=0.025) of median nerve in CMT1A patients was positively correlated with age at onset.MNCV (r=0.782,P=-0.013) of median nerve in MPZ-related CMT patients was positively correlated with age at onset.CMAP amplitude (r=0.652,P＜0.01) of median nerve in CMT2A patients was positively correlated with age at onset.Demyelination and axonal degeneration in male CMT1X patients were relatively more severe than those in female patients,and MNCV (Z=-3.300,P＜0.01) and CMAP amplitude (Z=-3.960,P＜0.01) of median nerve,MNCV (Z=-2.56,P=0.011) and CMAP amplitude (Z=-2.311,P=0.048) of ulnar nerve of male patients were lower than those of female patients.The ONLS score of CMT1A (r=-0.494,P＜0.01),CMT1X (r=-0.596,P＜0.01) and CMT2A patients (r=-0.494,P=0.012) was inversely associated with CMAP amplitude.Conclusions The electrophysiological characteristics of CMT1A,CMT1X,CMT2A and MPZ-related CMT are different.Electrophysiological examinations are the basis of clinical classification and could provide guidance for further genetic testing and diagnosis.CMAP amplitude may serve as an objective index to assess the severity of functional disability in CMT patients.

Objective:Hereditary neuropathy with liability to pressure palsy(HNPP)is a rare autosomal dominant peripheral neuropathy,usually caused by heterozygous deletion mutations in the peripheral myelin protein 22(PMP22)gene.This study aims to investigate the clinical and molecular genetic characteristics of HNPP. Methods:HNPP patients in the Department of Neurology at Third Xiangya Hospital of Central South University from 2009 to 2023 were included in this study.The general clinical data,nervous electrophysiological and molecular genetic examination results were collected and analyzed.Molecular genetic examination was to screen for deletion of PMP22 gene using multiplex ligation-dependent probe amplification(MLPA)after extracting genomic DNA from peripheral blood;and if no PMP22 deletion mutation was detected,next-generation sequencing was used to screen for PMP22 point mutations.The related literatures of HNPP were reviewed,and the clinical and molecular genetic characteristics of HNPP patients were analyzed. Results:A total of 34 HNPP patients from 24 unrelated Chinese Han families were included in this study,including 25 males and 9 females.The average age at illness onset was 22.0 years.Sixty-two point five percent of the families had a positive family history.Among them,30 patients had symptoms of peripheral nerve paralysis.Patients often presented with paroxysmal single limb weakness with(or)numbness(25/30),and some patients had paroxysmal unilateral recurrent laryngeal nerve(vagus nerve)paralysis(2/30).Physical examination revealed muscle weakness(23/29),hypoesthesia(9/29),weakened or absent ankle reflexes(20/29),distal limb muscle atrophy(8/29)and high arched feet(5/29).Most patients(26/30)could fully recover to normal after an acute attack.Thirty-one patients in our group underwent nervous electrophysiological examination,and showed multiple demyelinating peripheral neuropathies with both motor and sensory nerves involved.Most patients showed significantly prolonged distal motor latency(DML),mild to moderate nerve conduction velocity slowing,decreased amplitude of compound muscle action potential(CMAP)and sensory nerve action potential(SNAP),and sometimes with conduction block.Nerve motor conduction velocity was(48.5±5.5)m/s,and the CMAP amplitude was(8.4±5.1)mV.Nerve sensory conduction velocity was(37.4±10.5)m/s,and the SNAP amplitude was(14.4±15.2)μV.There were 24 families,23 of whom had the classical PMP22 deletion,the last one had a heterozygous pathogenic variant in the PMP22 gene sequence(c.434delT).By reviewing clinical data and genetic testing results of reported 1 734 HNPP families,we found that heterozygous deletion mutation of PMP22 was the most common pathogenic mutation of HNPP(93.4%).Other patients were caused by PMP22 small mutations(4.0%),PMP22 heterozygous gross deletions(0.6%),and PMP22 complex rearrangements(0.1%).Thirty-eight sorts of HNPP-related PMP22 small mutations was reported,including missense mutations(10/38),nonsense mutations(4/38),base deletion mutations(13/38),base insertion mutations(3/38),and shear site mutations(8/38).HNPP patients most often presented with episodic painless single nerve palsy.Common peroneal nerve,ulnar nerve,and brachial plexus nerve were the most common involved nerves,accounting for about 75%.Only eighteen patients with cranial nerve involved was reported. Conclusion:Heterozygous deletion mutation of PMP22 is the most common pathogenic mutation of HNPP.Patients is characterized by episodic and painless peripheral nerve paralysis,mainly involving common peroneal nerve,ulnar nerve,and other peripheral nerves.Nervous electrophysiological examination has high sensitivity and specificity for the diagnosis of HNPP,which is manifested by extensive demyelinating changes.For patients with suspected HNPP,nervous electrophysiological examination and PMP22-MLPA detection are preferred.Sanger sequencing or next generation sequencing can be considered to detect other mutations of PMP22.

Objective To evaluate the efficacy,safety and economy of teriparatide in the treatment of osteoporosis.Methods PubMed,Embase,Cochrane Library,Web of Science,CNKI,WanFang Data,VIP databases and websites related to health technology evaluation were systematically searched to collect high-quality clinical evidence and economic evaluation literature of teriparatide in the treatment of osteoporosis from the inception to January 20,2023.Two researchers independently identified studies,extracted data,assessed the quality of included studies,and descriptive analyzed and summarised the results.Results A total of 25 literatures were included,involving 3 HTA reports,15 systematic review/Meta-analyses and 7 economic studies were included.In terms of effectiveness,the evaluation results showed that teriparatide could improve bone mineral density in patients with osteoporosis,reduce the incidence of vertebral/non-vertebral fractures in primary and secondary osteoporosis and prevent the fractures in postmenopausal osteoporosis compared to bisphosphonates and placebos.In terms of safety,teriparatide was proven to be safe with no elevated risk of adverse drug reactions.In terms of economic cost,teriparatide has a higher cost and economic disadvantage compared with bisphosphonates,however,for people with severe postmenopausal osteoporosis and high risk of fracture,teriparatide can be considered as a potential cost-effect treatment option.Conclusion Teriparatide is effective and safe in the treatment of osteoporosis,but it is not cost-effective advantages compared with the existing other anti-osteoporosis medications.

Objective:To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2 (MORC2) gene-related neuropathy in Chinese patients. Methods:The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023. Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease. Results:A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed. Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families, including the novel variant c.1330G>C (p.G444R) that had not been previously reported. Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene (CMT2Z) phenotype with childhood or adult onset, and carried variants c.754C>T (p.R252W), c.1199A>G (p.Q400R), c.1330G>C (p.G444R), or c.1396G>A (p. D466N); 3 families manifested as severe spinal muscular atrophy (SMA)-like phenotype with infantile onset, all carried c.260C>T (p.S87L); 1 family carried c.1181A>G (p.Y394C), presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation. Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene, among which 5 families were associated with the CMT2Z phenotype, carrying c.754C>T (p.R252W), c.1079A>G (p.E360G), c.1220G>A (p.C407Y), or c.1397A>G (p.D466G); 1 family was associated with SMA-like phenotype, carrying c.260C>T (p.S87L); and 2 families were associated with DIGFAN syndrome, carrying c.79G>A (p.E27K) and c.292G>A (p.G98R). Conclusions:A novel pathogenic variant c.1330G>C (p.G444R) of the MORC2 gene associated with the CMT2 phenotype is reported. Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date, and c.754C>T(p.R252W) may be the most common. Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity, manifesting as CMT2Z, early-onset severe SMA-like myasthenia, or DIGFAN syndrome.