Objective To explore the effects and mechanism of Jianpi Shuyi Decoction in improving pancreatic fibrosis in chronic pancreatitis(CP)based on network pharmacology and animal experiments.Methods TCMSP was used to screen the active components and targets of Jianpi Shuyi Decoction.GeneCards was used to obtain the disease targets of pancreatic fibrosis,and the intersection of drug and disease targets was used to construct the protein interaction network and the drug-component-target network,and the core target genes were screened out.GO and KEGG pathway enrichment analysis was performed on the intersecting targets.Caerulein was used to induce CP mouse model,and Jianpi Shuyi Decoction was given for gavage.HE and Sirius red staining were used to observe pancreatic tissue inflammation and collagen deposition,respectively.RT-qPCR was used to observe the mRNA expression levels of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue.Immunohistochemistry staining was used to observe the protein expression levels of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissues.Results A total of 181 active components were screened from Jianpi Shuyi Decoction,corresponding to 284 targets,with 240 targets overlapping between drugs and disease and the core targets were PTGS2,HSP90AA1,etc.193 signaling pathways were obtained from KEGG pathway enrichment analysis,primarily involving lipids and atherosclerosis,chemical carcinogenic-receptor activation,PI3K-Akt signaling pathway and others.The results of animal experiments showed that,compared with the normal group,the model group showed a large number of inflammatory cell infiltration and collagen deposition in pancreatic tissue,the mRNA expression of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue significantly increased(P<0.01),and the protein expression of α-SMA,COL-1,p-PI3K,p-Akt significantly increased(P<0.01);Jianpi Shuyi Decoction significantly reduced the inflammation and collagen deposition in pancreas of mice,reduced the mRNA expression of Acta2,COL1A1,PI3K and Akt1(P<0.05),and attenuated the protein expression of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissue(P<0.05).Conclusion Jianpi Shuyi Decoction may exert a therapeutic effect on CP pancreatic fibrosis by regulating the PI3K/Akt signaling pathway,attenuating inflammation and collagen deposition in the pancreas,and reducing the levels of α-SMA and COL-1.

Objective:To investigate the clinical and genetic characteristics of patients with amyotrophic lateral sclerosis (ALS) caused by FUS gene mutations. Methods:A retrospective analysis was conducted on 7 families diagnosed with FUS gene related ALS in the Department of Neurology of Henan Provincial People′s Hospital from January 2018 to June 2024. Clinical data and neuroelectrophysiological results of the probands and family members were collected. Next generation sequencing or whole exome sequencing was conducted on the probands. The detected variants of the FUS gene were confirmed by Sanger sequencing. Results:Among the 7 probands, 4 were with familial ALS and 3 with sporadic ALS, including 6 males and 1 female. The average age of onset was 24.6 years (ranging from 21 to 30 years). The onset site included bulbar muscles in 1 case, proximal upper limbs in 3 cases, proximal lower limbs in 2 cases, and both upper and lower limbs in 1 case. Four patients presented both upper and lower motor neurons involvement on examination, and 3 had only lower motor neuron syndrome. Muscle atrophy and fasciculation were observed in 6 patients respectively, and dyspnea in 3 patients. Bilateral muscle strength was asymmetric in 5 patients. Proximal muscle weakness was predominant in 6 of the 7 patients with upper limb weakness, and 3 of the 5 patients with lower limb weakness. Electromyography showed neurogenic damage in all 7 cases. Five heterozygous variants of the FUS gene were detected in 7 patients, including 2 patients with c.1574C>T(p.P525L), 2 with c.1552A>G(p.R518G), 1 with c.1561C>T(p.R521C), 1 with c.1441delC(p.R481Efs *48), and 1 with both c.1574C>T(p.P525L) and c.430_447del(p.G144_Y149del) variants. The variant c.1441delC(p.R481Efs *48) had not been previously reported. During follow-up, 6 patients died of respiratory failure 6-18 months after onset, with an average of 11.8 months. Conclusions:Patients with FUS gene related ALS have an early age of onset, rapid progression, short survival period, asymmetric limb weakness, and more severe involvement of proximal limbs. The c.1574C>T(p.P525L) is a hotspot mutation, and the novel variant c.1441delC(p.R481Efs *48) enriches the mutation spectrum of the FUS gene.

Objective:To investigate the clinical and genetic characteristics of spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous mutations. Methods:Three SMA-Ⅲ pedigrees treated in Henan Provincial People′s Hospital from October 2019 to July 2020 were selected. The clinical data of 3 SMA-Ⅲ probands were retrospectively analyzed. Multiplex ligation-dependent probe amplification (MLPA) technology was used to detect the copy number of the SMN gene in the probands and their parents. Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMN1 gene of the probands. Sanger sequencing was used to validate candidate variant sites. Results:The 3 probands are all male, aged 19, 17 and 12 years, respectively. The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs, mild to moderate elevation of serum creatine kinase, and neurogenic injury as determined by electromyography or muscle pathology. The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMN1 gene, and carried heterozygous variations c.275G>A (p.Trp92 *), c.689C>T (p.Ser230Leu), and c.708dupT (p.Pro237Serfs *19), respectively. The exon deletion and point mutation were inherited separately from their parents. c. 275G>A (p.Trp92 *) and c.708dupT (p.Pro237Serfs *19) variations had not been reported before. Conclusions:The clinical manifestations of SMA-Ⅲ patients are symmetrical muscle weakness, mainly in the proximal extremities of both lower limbs, and electromyography or muscle biopsy suggesting neurogenic lesions. The compound heterozygous variation of point mutation and heterozygous deletion in the SMN1 gene can lead to SMA-Ⅲ. Suspected SMA patients with SMN1 gene heterozygous deletion should take point mutation testing.

Objective:To analyze the clinical manifestations and muscular magnetic resonance imaging (MRI) features of 12 families with facioscapulohumeral muscular dystrophy (FSHD).Methods:Retrospective analysis was conducted on 12 FSHD families diagnosed by genetic testing at the Department of Neurology of Henan Provincial People′s Hospital from January 2017 to June 2021. Clinical data and lower limb muscle MRI results of the probands and related members of the families were collected, and the degree of muscle fatty degeneration shown in the MRI was scored using the modified Mercuri score.Results:There were 21 patients in 12 families, with the age of onset ranged from 10 to 47 years (mean 19.5 years). The course of disease ranged from 1 to 47 years (mean 23.1 years). The onset sites included unilateral upper extremity in 8 cases, bilateral proximal upper extremities in 9 cases, bilateral proximal lower extremities in 2 cases, unilateral proximal lower extremity in 1 case, and simultaneous onset in all 4 limbs in 1 case. Sixteen patients had limb weakness and bilateral asymmetry, and 11/16 cases were more severe on the right side than the left side. Winged scapular and facial muscle weakness were observed in all patients. The creatine kinase range was 85-1 038 U/L (461 U/L on average) in 12/21 cases. There were 10/21 cases of myogenic lesion in electromyography. Myodystroph-like pathological changes were found in 11/21 cases. The fragment length of the 4q35 subtelomere polymorphism EcoRI/p13E-11 was less than 38 kb in 20/21 cases; 1 case was confirmed based on clinical symptoms and family history. Fat infiltration occurred in at least one muscle of lower limbs in 9/10 cases, in thigh muscle in 9/10 cases and in calf muscle in 6/10 cases. The average score of fat infiltration in thigh muscle group was higher than that in calf muscle group. The muscles with higher fat infiltration scores were the vastus intermedius, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, the vastus lateralis in the thigh (with score ≥2.15), the tibialis anterior, and the medial head of the gastrocnemius in the calf (with score ≥1.11). Fat infiltration in the medial and posterior thigh muscles was more common than in the anterior thigh muscles. There was asymmetry of bilateral muscle fat in 9/10 cases. There were edematous changes in thigh muscles in 1 case and in calf muscles in 3 cases.Conclusions:The age of onset of FSHD patients is mostly ≤30 years. Bilateral asymmetric involvement is the characteristic manifestation of FSHD. The FSHD patients ' muscles most affected by the disease in the thigh are the quadriceps femoris, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, and the vastus intermedius. In the calf, the muscles most affected are the anterior tibial muscle and the medial head of the gastrocnemius. The MRI pattern of muscle involvement of patients with FSHD is bilateral asymmetrical lesions, with the right side having more severe lesions. The fatization of thigh muscles is more significant than that of calf muscles, and the asymmetry of fatization between bilateral muscles is also present.

Objective:To investigate the clinical and genetic characteristics of patients with amyotrophic lateral sclerosis (ALS) caused by FUS gene mutations. Methods:A retrospective analysis was conducted on 7 families diagnosed with FUS gene related ALS in the Department of Neurology of Henan Provincial People′s Hospital from January 2018 to June 2024. Clinical data and neuroelectrophysiological results of the probands and family members were collected. Next generation sequencing or whole exome sequencing was conducted on the probands. The detected variants of the FUS gene were confirmed by Sanger sequencing. Results:Among the 7 probands, 4 were with familial ALS and 3 with sporadic ALS, including 6 males and 1 female. The average age of onset was 24.6 years (ranging from 21 to 30 years). The onset site included bulbar muscles in 1 case, proximal upper limbs in 3 cases, proximal lower limbs in 2 cases, and both upper and lower limbs in 1 case. Four patients presented both upper and lower motor neurons involvement on examination, and 3 had only lower motor neuron syndrome. Muscle atrophy and fasciculation were observed in 6 patients respectively, and dyspnea in 3 patients. Bilateral muscle strength was asymmetric in 5 patients. Proximal muscle weakness was predominant in 6 of the 7 patients with upper limb weakness, and 3 of the 5 patients with lower limb weakness. Electromyography showed neurogenic damage in all 7 cases. Five heterozygous variants of the FUS gene were detected in 7 patients, including 2 patients with c.1574C>T(p.P525L), 2 with c.1552A>G(p.R518G), 1 with c.1561C>T(p.R521C), 1 with c.1441delC(p.R481Efs *48), and 1 with both c.1574C>T(p.P525L) and c.430_447del(p.G144_Y149del) variants. The variant c.1441delC(p.R481Efs *48) had not been previously reported. During follow-up, 6 patients died of respiratory failure 6-18 months after onset, with an average of 11.8 months. Conclusions:Patients with FUS gene related ALS have an early age of onset, rapid progression, short survival period, asymmetric limb weakness, and more severe involvement of proximal limbs. The c.1574C>T(p.P525L) is a hotspot mutation, and the novel variant c.1441delC(p.R481Efs *48) enriches the mutation spectrum of the FUS gene.

Objective:To investigate the clinical and genetic characteristics of spinal muscular atrophy (SMA) patients with SMN1 gene compound heterozygous mutations. Methods:Three SMA-Ⅲ pedigrees treated in Henan Provincial People′s Hospital from October 2019 to July 2020 were selected. The clinical data of 3 SMA-Ⅲ probands were retrospectively analyzed. Multiplex ligation-dependent probe amplification (MLPA) technology was used to detect the copy number of the SMN gene in the probands and their parents. Polymerase chain reaction amplification combined with microfluidic capillary electrophoresis were used to detect point mutations in the SMN1 gene of the probands. Sanger sequencing was used to validate candidate variant sites. Results:The 3 probands are all male, aged 19, 17 and 12 years, respectively. The main clinical manifestations were symmetrical muscle weakness mainly in the proximal lower limbs, mild to moderate elevation of serum creatine kinase, and neurogenic injury as determined by electromyography or muscle pathology. The genetic testing results showed that all 3 probands had heterozygous deletion in exon 7 of the SMN1 gene, and carried heterozygous variations c.275G>A (p.Trp92 *), c.689C>T (p.Ser230Leu), and c.708dupT (p.Pro237Serfs *19), respectively. The exon deletion and point mutation were inherited separately from their parents. c. 275G>A (p.Trp92 *) and c.708dupT (p.Pro237Serfs *19) variations had not been reported before. Conclusions:The clinical manifestations of SMA-Ⅲ patients are symmetrical muscle weakness, mainly in the proximal extremities of both lower limbs, and electromyography or muscle biopsy suggesting neurogenic lesions. The compound heterozygous variation of point mutation and heterozygous deletion in the SMN1 gene can lead to SMA-Ⅲ. Suspected SMA patients with SMN1 gene heterozygous deletion should take point mutation testing.

Objective:To analyze the clinical manifestations and muscular magnetic resonance imaging (MRI) features of 12 families with facioscapulohumeral muscular dystrophy (FSHD).Methods:Retrospective analysis was conducted on 12 FSHD families diagnosed by genetic testing at the Department of Neurology of Henan Provincial People′s Hospital from January 2017 to June 2021. Clinical data and lower limb muscle MRI results of the probands and related members of the families were collected, and the degree of muscle fatty degeneration shown in the MRI was scored using the modified Mercuri score.Results:There were 21 patients in 12 families, with the age of onset ranged from 10 to 47 years (mean 19.5 years). The course of disease ranged from 1 to 47 years (mean 23.1 years). The onset sites included unilateral upper extremity in 8 cases, bilateral proximal upper extremities in 9 cases, bilateral proximal lower extremities in 2 cases, unilateral proximal lower extremity in 1 case, and simultaneous onset in all 4 limbs in 1 case. Sixteen patients had limb weakness and bilateral asymmetry, and 11/16 cases were more severe on the right side than the left side. Winged scapular and facial muscle weakness were observed in all patients. The creatine kinase range was 85-1 038 U/L (461 U/L on average) in 12/21 cases. There were 10/21 cases of myogenic lesion in electromyography. Myodystroph-like pathological changes were found in 11/21 cases. The fragment length of the 4q35 subtelomere polymorphism EcoRI/p13E-11 was less than 38 kb in 20/21 cases; 1 case was confirmed based on clinical symptoms and family history. Fat infiltration occurred in at least one muscle of lower limbs in 9/10 cases, in thigh muscle in 9/10 cases and in calf muscle in 6/10 cases. The average score of fat infiltration in thigh muscle group was higher than that in calf muscle group. The muscles with higher fat infiltration scores were the vastus intermedius, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, the vastus lateralis in the thigh (with score ≥2.15), the tibialis anterior, and the medial head of the gastrocnemius in the calf (with score ≥1.11). Fat infiltration in the medial and posterior thigh muscles was more common than in the anterior thigh muscles. There was asymmetry of bilateral muscle fat in 9/10 cases. There were edematous changes in thigh muscles in 1 case and in calf muscles in 3 cases.Conclusions:The age of onset of FSHD patients is mostly ≤30 years. Bilateral asymmetric involvement is the characteristic manifestation of FSHD. The FSHD patients ' muscles most affected by the disease in the thigh are the quadriceps femoris, the long head of the biceps femoris, the vastus medialis, the vastus lateralis, the semitendinosus, the semimembranosus, and the vastus intermedius. In the calf, the muscles most affected are the anterior tibial muscle and the medial head of the gastrocnemius. The MRI pattern of muscle involvement of patients with FSHD is bilateral asymmetrical lesions, with the right side having more severe lesions. The fatization of thigh muscles is more significant than that of calf muscles, and the asymmetry of fatization between bilateral muscles is also present.

Objective To explore the effects and mechanism of Jianpi Shuyi Decoction in improving pancreatic fibrosis in chronic pancreatitis(CP)based on network pharmacology and animal experiments.Methods TCMSP was used to screen the active components and targets of Jianpi Shuyi Decoction.GeneCards was used to obtain the disease targets of pancreatic fibrosis,and the intersection of drug and disease targets was used to construct the protein interaction network and the drug-component-target network,and the core target genes were screened out.GO and KEGG pathway enrichment analysis was performed on the intersecting targets.Caerulein was used to induce CP mouse model,and Jianpi Shuyi Decoction was given for gavage.HE and Sirius red staining were used to observe pancreatic tissue inflammation and collagen deposition,respectively.RT-qPCR was used to observe the mRNA expression levels of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue.Immunohistochemistry staining was used to observe the protein expression levels of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissues.Results A total of 181 active components were screened from Jianpi Shuyi Decoction,corresponding to 284 targets,with 240 targets overlapping between drugs and disease and the core targets were PTGS2,HSP90AA1,etc.193 signaling pathways were obtained from KEGG pathway enrichment analysis,primarily involving lipids and atherosclerosis,chemical carcinogenic-receptor activation,PI3K-Akt signaling pathway and others.The results of animal experiments showed that,compared with the normal group,the model group showed a large number of inflammatory cell infiltration and collagen deposition in pancreatic tissue,the mRNA expression of Acta2,COL1A1,PI3K and Akt1 in pancreatic tissue significantly increased(P<0.01),and the protein expression of α-SMA,COL-1,p-PI3K,p-Akt significantly increased(P<0.01);Jianpi Shuyi Decoction significantly reduced the inflammation and collagen deposition in pancreas of mice,reduced the mRNA expression of Acta2,COL1A1,PI3K and Akt1(P<0.05),and attenuated the protein expression of α-SMA,COL-1,p-PI3K and p-Akt in pancreatic tissue(P<0.05).Conclusion Jianpi Shuyi Decoction may exert a therapeutic effect on CP pancreatic fibrosis by regulating the PI3K/Akt signaling pathway,attenuating inflammation and collagen deposition in the pancreas,and reducing the levels of α-SMA and COL-1.

Frontotemporal dementia (FTD) is a group of dementia diseases mainly characterized by progressive mental-behavioral abnormalities, executive dysfunction, and language impairment. A small number of FTD patients also present with movement disorders at certain disease course. Here the clinical and multimodal positron-emission tomography (PET) imaging manifestations in a patient with frontotemporal lobe dementia and parkinsonian syndrome are reported. 18F-fluorodopa PET showed reduced uptake in the head of the caudate nucleus. 18F-AV-45 PET showed negative amyloid deposition. 18F-AV-1451 PET showed tau deposition in the neocortex. The clinical and neuroimaging features support the underlying frontotemporal lobar degeneration-tau pathology.

Humans ; SARS-CoV-2 ; COVID-19