The proband was a 32-year-old female patient who sought medical attention for over 9 months of pregnancy, reduced fetal movement, and discomfort in the lower abdomen. The proband and her father had normal activated partial thromboplastin time and prothrombin time, decreased fibrinogen activity and antigen levels, and prolonged thrombin time, whereas the test results of her mother were normal. Ultrasonography showed intermuscular vein thrombosis in the left calf of the proband. Peripheral blood DNA was extracted from the proband and her parents, and Sanger sequencing was performed to detect the base sequences of the FGA, FGB, and FGG genes. The proband and her father had heterozygous missense mutations in exon 6 c.615A > C (p. Leu205Phe) and exon 8 c.1121A > C (p. Tyr374Ser) of the FGG gene. Bioinformatics analysis suggested that the two gene mutations may be the pathogenic mechanism of this congenital hypodysfibrinogenemia family.

Objective:To explore the effect of combining intermittent θ pulse stimulation (iTBS) of the cerebellum with lower extremity exoskeleton robot support on the balance and walking function of stroke survivors.Methods:Seventy-five stroke survivors complicated with lower extremity dysfunction were divided into an iTBS group, an exoskeleton group and a combined group, each of 25, according to a random number table. In addition to conventional rehabilitation training, the iTBS group was given cerebellar iTBS combined with traditional walking training, the exoskeleton group received sham cerebellar iTBS combined with walking training assisted by a lower extremity exoskeleton robot. The combined group received both therapies. The schedule was once a day, 5 days a week for 3 weeks. Before and after the treatment, the 10-metre walking test (10MWT), the Berg Balance Scale (BBS) and the Fugl-Meyer lower extremity assessment (FMA-LE) were used to evaluate the subjects′ walking ability, balance and lower extremity motor ability. Gait and neuro-electrophysiological tests were also conducted in all three groups.Results:After the treatment, a significant improvement was observed in the 10MWT times, BBS scores, FMA-LE scores, stride frequency and stride speed of all three groups compared with before the treatment. On average, the results of the exoskeleton and combined groups were significantly better than those of the iTBS group, and those of the combined group were significantly better than among the exoskeleton group. Almost everyone′s MEP latency and amplitude had improved significantly compared with before the treatment, but the improvements in the exoskeleton group tended to be superior to those in the iTBS group ( P≤0.05). The latency in the combined group averaged (21.25±1.70)ms, and the amplitude averaged (184.17±6.54)μV, both significantly better than the exoskeleton group′s averages. Conclusions:Cerebellum iTBS combined with lower extremity exoskeleton walker training can significantly improve the motor functioning, balance and walking ability of stroke survivors.

Objective:To explore the effect of combining repeated peripheral (rPMS) and central transcranial magnetic stimulation (rTMS) in treating upper limb motor dysfunction after a stroke.Methods:Seventy-eight patients with upper limb motor dysfunction after a stroke were randomly divided into a control group, an rTMS group and a combined magnetic stimulation group, each of 26. All three groups underwent routine rehabilitation, while the rTMS group was repeatedly given low frequency transcranial magnetic stimulation of the M1 region on the unaffected side, and the combined group also received repeated peripheral magnetic stimulation at Erb′s point on the affected upper limb. There was one treatment session a day, 5 days a week for 3 weeks. Before and after the treatment, everyone′s upper limb motor function was quantified using the Fugl-Meyer upper extremity assessment (FMA-UE) and the Wolf motor function test (WMFT). Skill in the activities of daily living was quantified in terms of a Barthel index (BI). Motor recovery of the upper limbs and hands was assessed using Brunnstrom staging. The latency and amplitude of the motor evoked potentials (MEPs) in the subjects′ affected abductor pollicis brevis muscles were also recorded before and after the treatment. Pearson correlation coefficients quantified the correlation between the changes in FMA-UE scores and MEP amplitudes before and after the treatment in the three groups.Results:There were no significant differences among the three groups before the treatment. Afterward, however, the average FMA-UE, WMFT and BI scores, as well as the upper limb and hand Brunnstrom stages and the average MEP latencies and amplitudes of all the three groups had improved significantly. The combined group′s average results were then significantly better than the other two groups′ averages, except for the upper limb Brunnstrom stages. The increases in MEP amplitude were positively correlated with the increases in FMA-UE scores among the rTMS and the combined group, but there was no significant correlation between them in the control group.Conclusions:The combined application of rPMS and contralateral low frequency rTMS can effectively relieve motor dysfunction in the upper limbs in the early stages after a stroke.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

Objective:To observe the effect of combining transcutaneous stimulation of the auricular vagus nerve (taVNS) with modified constraint-induced movement therapy (mCIMT) on the upper limb function of hemiplegic stroke survivors.Methods:Seventy-one hemiplegic stroke survivors were randomly divided into a taVNS group of 24, an mCIMT group of 23 and a combined group of 24. In addition to conventional rehabilitation therapy, the taVNS group received taVNS therapy, the mCIMT group received mCIMT, while the combined group received both for 30 minutes a day, 5 days a week for 4 weeks. Before and after the treatment, everyone′s upper limb function was evaluated using the Fugl-Meyer upper extremity assessment (FMA-UE) and the Action Research arm test (ARAT). Ability in the activities of daily living (ADL) was quantified using the modified Barthel index (MBI). The latency and amplitude of motor evoked potentials (MEPs) were also measured.Results:After the treatment, significant improvement was observed in the average FMA-UE, ARAT and MBI scores. MEP latency and amplitude had also improved. The averages in the mCIMT group were then significantly better than among the taVNS group.Conclusions:taVNS combined with mCIMT can significantly improve the upper limb function and ADL functioning of stroke survivors with hemiplegia. It can also promote the recovery of central nervous system function.

Objective:To observe the effect of combining transcutaneous stimulation of the auricular vagus nerve (taVNS) with modified constraint-induced movement therapy (mCIMT) on the upper limb function of hemiplegic stroke survivors.Methods:Seventy-one hemiplegic stroke survivors were randomly divided into a taVNS group of 24, an mCIMT group of 23 and a combined group of 24. In addition to conventional rehabilitation therapy, the taVNS group received taVNS therapy, the mCIMT group received mCIMT, while the combined group received both for 30 minutes a day, 5 days a week for 4 weeks. Before and after the treatment, everyone′s upper limb function was evaluated using the Fugl-Meyer upper extremity assessment (FMA-UE) and the Action Research arm test (ARAT). Ability in the activities of daily living (ADL) was quantified using the modified Barthel index (MBI). The latency and amplitude of motor evoked potentials (MEPs) were also measured.Results:After the treatment, significant improvement was observed in the average FMA-UE, ARAT and MBI scores. MEP latency and amplitude had also improved. The averages in the mCIMT group were then significantly better than among the taVNS group.Conclusions:taVNS combined with mCIMT can significantly improve the upper limb function and ADL functioning of stroke survivors with hemiplegia. It can also promote the recovery of central nervous system function.

The proband was a 32-year-old female patient who sought medical attention for over 9 months of pregnancy, reduced fetal movement, and discomfort in the lower abdomen. The proband and her father had normal activated partial thromboplastin time and prothrombin time, decreased fibrinogen activity and antigen levels, and prolonged thrombin time, whereas the test results of her mother were normal. Ultrasonography showed intermuscular vein thrombosis in the left calf of the proband. Peripheral blood DNA was extracted from the proband and her parents, and Sanger sequencing was performed to detect the base sequences of the FGA, FGB, and FGG genes. The proband and her father had heterozygous missense mutations in exon 6 c.615A > C (p. Leu205Phe) and exon 8 c.1121A > C (p. Tyr374Ser) of the FGG gene. Bioinformatics analysis suggested that the two gene mutations may be the pathogenic mechanism of this congenital hypodysfibrinogenemia family.

Objective:To explore the effect of combining intermittent θ pulse stimulation (iTBS) of the cerebellum with lower extremity exoskeleton robot support on the balance and walking function of stroke survivors.Methods:Seventy-five stroke survivors complicated with lower extremity dysfunction were divided into an iTBS group, an exoskeleton group and a combined group, each of 25, according to a random number table. In addition to conventional rehabilitation training, the iTBS group was given cerebellar iTBS combined with traditional walking training, the exoskeleton group received sham cerebellar iTBS combined with walking training assisted by a lower extremity exoskeleton robot. The combined group received both therapies. The schedule was once a day, 5 days a week for 3 weeks. Before and after the treatment, the 10-metre walking test (10MWT), the Berg Balance Scale (BBS) and the Fugl-Meyer lower extremity assessment (FMA-LE) were used to evaluate the subjects′ walking ability, balance and lower extremity motor ability. Gait and neuro-electrophysiological tests were also conducted in all three groups.Results:After the treatment, a significant improvement was observed in the 10MWT times, BBS scores, FMA-LE scores, stride frequency and stride speed of all three groups compared with before the treatment. On average, the results of the exoskeleton and combined groups were significantly better than those of the iTBS group, and those of the combined group were significantly better than among the exoskeleton group. Almost everyone′s MEP latency and amplitude had improved significantly compared with before the treatment, but the improvements in the exoskeleton group tended to be superior to those in the iTBS group ( P≤0.05). The latency in the combined group averaged (21.25±1.70)ms, and the amplitude averaged (184.17±6.54)μV, both significantly better than the exoskeleton group′s averages. Conclusions:Cerebellum iTBS combined with lower extremity exoskeleton walker training can significantly improve the motor functioning, balance and walking ability of stroke survivors.

Objective:To explore the effect of combining repeated peripheral (rPMS) and central transcranial magnetic stimulation (rTMS) in treating upper limb motor dysfunction after a stroke.Methods:Seventy-eight patients with upper limb motor dysfunction after a stroke were randomly divided into a control group, an rTMS group and a combined magnetic stimulation group, each of 26. All three groups underwent routine rehabilitation, while the rTMS group was repeatedly given low frequency transcranial magnetic stimulation of the M1 region on the unaffected side, and the combined group also received repeated peripheral magnetic stimulation at Erb′s point on the affected upper limb. There was one treatment session a day, 5 days a week for 3 weeks. Before and after the treatment, everyone′s upper limb motor function was quantified using the Fugl-Meyer upper extremity assessment (FMA-UE) and the Wolf motor function test (WMFT). Skill in the activities of daily living was quantified in terms of a Barthel index (BI). Motor recovery of the upper limbs and hands was assessed using Brunnstrom staging. The latency and amplitude of the motor evoked potentials (MEPs) in the subjects′ affected abductor pollicis brevis muscles were also recorded before and after the treatment. Pearson correlation coefficients quantified the correlation between the changes in FMA-UE scores and MEP amplitudes before and after the treatment in the three groups.Results:There were no significant differences among the three groups before the treatment. Afterward, however, the average FMA-UE, WMFT and BI scores, as well as the upper limb and hand Brunnstrom stages and the average MEP latencies and amplitudes of all the three groups had improved significantly. The combined group′s average results were then significantly better than the other two groups′ averages, except for the upper limb Brunnstrom stages. The increases in MEP amplitude were positively correlated with the increases in FMA-UE scores among the rTMS and the combined group, but there was no significant correlation between them in the control group.Conclusions:The combined application of rPMS and contralateral low frequency rTMS can effectively relieve motor dysfunction in the upper limbs in the early stages after a stroke.

Objective:The phenotype and genotype of a pedigree with Glanzmann thrombasthenia caused by compound heterozygous mutation in the ITGA2B gene and its molecular pathogenesis were explored.Methods:The platelet aggregation rate of the proband and his family was detected by using a platelet aggregation test with adenosine diphosphate, collagen, epinephrine, arachidonic acid, and ristocetin. The expression levels of CD41 (αⅡb), CD61 (β3), and CD42b (GPⅠb) on the platelet surface was detected by flow cytometry. Gene sequencing technology was used for the genetic identification of the family. RT-PCR was used in the detection of mRNA splicing, and qRT-PCR was used in detecting the relative mRNA level of the ITGA2B gene. Bioinformatics analysis was used to evaluate the pathogenicity of mutation sites and their effects on protein structure and function. The expressions of total αⅡb and β3 in platelets were analyzed by Western blot.Results:Except ristocetin, the other four inducers could not induce platelet aggregation in the proband. Flow cytometry showed that the expression levels of αⅡb and β3 were only 0.25% and 9.76%, respectively, on the platelet surface of the proband, whereas GPⅠb expression was relatively normal. The expression levels of glycoproteins in the other family members were almost normal. c.480C>G and c.2929C>T mutations were detected in the proband through gene sequencing. The c.480C>G mutation was inherited from his mother, and the c.2929C>T mutation was inherited from his father. The RT-PCR and sequencing results showed that the c.480C>G mutation caused mRNA splicing in the proband and his mother, resulting in the deletion of 99 bases in c.476G-574A (p.S160-S192). qRT-PCR showed that the c.2929C>T variant reduced the mRNA level of the ITGA2B gene in the proband and his father. Bioinformatics analysis suggested that the c.480C>G mutation might form a binding sequence with hnRNP A1 protein and generate the 5′SS splice site. The three-dimensional structural model of the αⅡb subunit showed that the β-propeller domain of the p.S160-S192 deletion lost two β-strands and one α-helix in blade 2. The c.2929C>T nonsense mutation caused premature translation termination and produced a truncated protein with the deletion of p.R977-E1039, including the cytoplasmic domain, transmembrane domain, and a β chain of the extracellular Calf-2 domain. The total αⅡb expression of the proband was absent, and the relative expression of β3 was 11.36% of the normal level.Conclusion:The compound heterozygous mutation c.480C>G in exon 4 and c.2929C>T in exon 28 of the ITGA2B gene probably underlies Glanzmann thrombasthenia in this pedigree.