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 1-year postoperative efficacy of four bariatric procedures, namely sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S), and biliopancreatic diversion with duodenal switch (BPD/DS) for treating super obesity.Methods:In this retrospective observational study, we analyzed the clinical data of 40 patients with super obesity (body mass index [BMI]≥50 kg/m 2) who had undergone bariatric surgery in the China-Japan Union Hospital of Jilin University from November 2015 to December 2020. The study cohort consisted of 21 men and 19 women of average age 31.7±9.0 years. The preoperative weight and BMI were (159.2±16.9) kg and (53.4±3.0) kg/m 2, respectively. Prior to the surgery, 30 individuals had hypertension, 27 hyperuricemia, 15 type 2 diabetes, 10 abnormally high total cholesterol, 20 abnormally high triglycerides, and 24 abnormally high low-density lipoprotein. We divided the participants into four groups according to the type of operation: SG group ( n=16), RYGB group ( n=9), SADI-S group ( n=9) and BPD/DS group ( n=6). We examined the following factors: weight, BMI, excess weight loss (%), total weight loss (%), and remission of preoperative metabolic diseases (including hypertension, hyperuricemia, type 2 diabetes, and hyperlipidemia) 3, 6, and 12 months after surgery. The variables assessed for hypertension were systolic and diastolic blood pressure; for type 2 diabetes, glycated hemoglobin; and for hyperlipidemia, total cholesterol, triglycerides, and low-density lipoprotein 1-year after the surgery. The safety of surgery was also assessed. Results:All patients successfully completed laparoscopic procedures, none of them requiring conversion to laparotomy. The amount of blood loss during surgery was less than 50 mL. Postoperative hospital stay was 6–16 days. There were no deaths during the perioperative period. However, two postoperative complications occurred in the RYGB group, namely bleeding and anastomotic leakage. No complications were detected in the other groups. At 3, 6, and 12 months after surgery, percentage of excess weight loss was 36.6±11.0, 62.4±15.7, and 68.2±16.0 ( F=21.830, P<0.001) in the SG group; 30.6±6.9, 42.5±5.8, and 50.6±11.1 ( F=13.222, P<0.001) in the RYGB group; 39.7±7.8, 54.6±12.7, and 81.9±12.0 ( F=33.821, P<0.001) in the SADI-S group; and 40.2±4.8, 57.7±11.8, and 82.8±14.9 ( F=21.552, P<0.001), respectively, in the BPD/DS group. The percentage of excess weight loss increased significantly over the 12-month observation period in all groups . Compared with before surgery, hypertension and hyperuricemia in the SG, SADI-S, and BPD-DS groups showed significant improvement after one year (all P<0.05). However, only the SADI-S group exhibited a significant decrease in glycosylated hemoglobin concentrations ( P=0.038). Only the BPD-DS group showed significant decreases in various indicators of hyperlipidemia (all P<0.05). The improvements in obesity-related complication indexes did not reach statistical significance in the RYGB group (all P>0.05). Conclusion:SG, RYGB, SADI-S and BPD/DS are all safe and effective treatments for super obesity. All of these procedures can improve the associated metabolic diseases to a certain extent.

Objective:To evaluate the 1-year postoperative efficacy of four bariatric procedures, namely sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), single anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S), and biliopancreatic diversion with duodenal switch (BPD/DS) for treating super obesity.Methods:In this retrospective observational study, we analyzed the clinical data of 40 patients with super obesity (body mass index [BMI]≥50 kg/m 2) who had undergone bariatric surgery in the China-Japan Union Hospital of Jilin University from November 2015 to December 2020. The study cohort consisted of 21 men and 19 women of average age 31.7±9.0 years. The preoperative weight and BMI were (159.2±16.9) kg and (53.4±3.0) kg/m 2, respectively. Prior to the surgery, 30 individuals had hypertension, 27 hyperuricemia, 15 type 2 diabetes, 10 abnormally high total cholesterol, 20 abnormally high triglycerides, and 24 abnormally high low-density lipoprotein. We divided the participants into four groups according to the type of operation: SG group ( n=16), RYGB group ( n=9), SADI-S group ( n=9) and BPD/DS group ( n=6). We examined the following factors: weight, BMI, excess weight loss (%), total weight loss (%), and remission of preoperative metabolic diseases (including hypertension, hyperuricemia, type 2 diabetes, and hyperlipidemia) 3, 6, and 12 months after surgery. The variables assessed for hypertension were systolic and diastolic blood pressure; for type 2 diabetes, glycated hemoglobin; and for hyperlipidemia, total cholesterol, triglycerides, and low-density lipoprotein 1-year after the surgery. The safety of surgery was also assessed. Results:All patients successfully completed laparoscopic procedures, none of them requiring conversion to laparotomy. The amount of blood loss during surgery was less than 50 mL. Postoperative hospital stay was 6–16 days. There were no deaths during the perioperative period. However, two postoperative complications occurred in the RYGB group, namely bleeding and anastomotic leakage. No complications were detected in the other groups. At 3, 6, and 12 months after surgery, percentage of excess weight loss was 36.6±11.0, 62.4±15.7, and 68.2±16.0 ( F=21.830, P<0.001) in the SG group; 30.6±6.9, 42.5±5.8, and 50.6±11.1 ( F=13.222, P<0.001) in the RYGB group; 39.7±7.8, 54.6±12.7, and 81.9±12.0 ( F=33.821, P<0.001) in the SADI-S group; and 40.2±4.8, 57.7±11.8, and 82.8±14.9 ( F=21.552, P<0.001), respectively, in the BPD/DS group. The percentage of excess weight loss increased significantly over the 12-month observation period in all groups . Compared with before surgery, hypertension and hyperuricemia in the SG, SADI-S, and BPD-DS groups showed significant improvement after one year (all P<0.05). However, only the SADI-S group exhibited a significant decrease in glycosylated hemoglobin concentrations ( P=0.038). Only the BPD-DS group showed significant decreases in various indicators of hyperlipidemia (all P<0.05). The improvements in obesity-related complication indexes did not reach statistical significance in the RYGB group (all P>0.05). Conclusion:SG, RYGB, SADI-S and BPD/DS are all safe and effective treatments for super obesity. All of these procedures can improve the associated metabolic diseases to a certain extent.

Objective To investigate the intervention effect and mechanism of sinomenine(SIN)on Parkinson's disease(PD)mice based on GSK3 β/Nrf2/HO-1 and NF-κ B signaling pathways.Methods C57BL/6 mice were randomly divided into 6 groups:normal group,model group,positive drug group(Levodopa,75 mg?kg-1)and SIN low-,medium-and high-dose groups(20,40,80 mg?kg-1),with 8 mice in each group.Mice were intraperitoneally injected with 20 mg?kg-1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)once a day for 5 days.Intragastric administration was performed 1 hour after injection of MPTP,once a day for 12 days.On the day 11 of administration,the mice were subjected to a pole-climbing experiment,and on the day 12,a rotating rod experiment was performed to test the behavioral changes of the mice.The levels of serum tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 were detected by ELISA.The mRNA expression levels of TNF-α,IL-1β and IL-6 in brain tissue were detected by RT-qPCR.The protein expression levels of TH,Nrf2,HO-1,p-GSK3β,GSK3β,p-IκB,IκB,p-NF-κB and NF-κB in brain tissue were detected by Western Blot.Results Compared with the normal group,the automatic turning latency(T-turn)of the model group was significantly prolonged(P＜0.05),and the number of falls was significantly increased(P＜0.001).The expression level of TH protein in brain tissue was significantly decreased(P＜0.01),and the mRNA expression levels of IL-1β,TNF-α and IL-6 were significantly increased(P＜0.001).The serum levels of TNF-α,IL-1β and IL-6 were significantly increased(P＜0.05,P＜0.01).The protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly decreased(P＜0.05,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly increased(P＜0.001).Compared with the model group,the T-turn in the Sin medium-and high-dose groups was significantly shortened(P＜0.05,P＜0.001),the falling latency was significantly prolonged(P＜0.05,P＜0.01),the times of falls was significantly reduced(P＜0.001),the expression level of TH protein in brain tissue was significantly increased(P＜0.01,P＜0.001),and the level of serum TNF-α was significantly decreased(P＜0.05).The mRNA expression levels of IL-1β,TNF-α and IL-6 in brain tissue of mice in each administration group were significantly decreased(P＜0.001),the serum levels of IL-1β and IL-6 were significantly decreased(P＜0.01,P＜0.001),the protein expression levels of p-GSK3β/GSK3β,Nrf2 and HO-1 in brain tissue were significantly increased(P＜0.05,P＜0.01,P＜0.001),and the protein expression ratios of p-IκB/IκB and p-NF-κB/NF-κB were significantly decreased(P＜0.001).Conclusion SIN can enhance anti-oxidative stress and inhibit neuroinflammation by regulating GSK3β/Nrf2/HO-1 and NF-κB pathways in the brain of Parkinson's disease mice,thereby exerting neuroprotective effects.

The construction of experimental animal models plays an important supporting role in research into the mechanisms of action of Chinese medicines.There have been increasing reports of the construction and evaluation of animal models of spleen deficiency;however,the construction method have involved different standards and there has been insufficient objectification of the evaluation indexes.In this review,we summarize the construction and evaluation method of animal models of spleen deficiency from the aspects of animal selection,model establishment,macroscopic characterization,behavioral experiments,and objective indexes of spleen deficiency,with a view to providing theoretical guidance for the construction of experimental animal models of spleen deficiency and references for the selection of animal model platforms for spleen deficiency.

Due to the virtues of no stutter peaks, low rates of mutation, and short amplicon sizes, insertion/deletion (InDel) polymorphism is an indispensable tool for analyzing degraded DNA samples from crime scenes for human identifications (Wang et al., 2021). Herein, a self-developed panel of 43 InDel loci constructed previously by our group was utilized to evaluate the genetic diversities and explore the genetic background of the Han Chinese from Beijing (HCB) including 301 random healthy individuals. The lengths of amplicons at 43 InDel loci in this panel ranged from 87 to 199 bp, which indicated that the panel could be used as an effective tool to utilize highly degraded DNA samples for human identity testing. The loci in this panel were validated and performed well for forensic degraded DNA samples (Jin et al., 2021). The combined discrimination power (PD) and combined probability of exclusion (PE) values in this panel indicated that the 43 InDel loci could be used as the candidate markers in personal identification and parentage testing of HCB. In addition, population genetic relationships between the HCB and 26 reference populations from five continents based on 19 overlapped InDel loci were displayed by constructing a phylogenetic tree, principal component analysis (PCA), and population genetic structure analysis. The results illustrated that the HCB had closer genetic relationships with the Han populations from Chinese different regions.
Beijing ; China ; Forensic Genetics/methods* ; Gene Frequency ; Genetics, Population ; Humans ; INDEL Mutation ; Phylogeny

Gliomas are the most common central nervous system tumours; they are highly aggressive and have a poor prognosis. RGS16 belongs to the regulator of G-protein signalling (RGS) protein family, which plays an important role in promoting various cancers, such as breast cancer, pancreatic cancer, and colorectal cancer. Moreover, previous studies confirmed that let-7c-5p, a well-known microRNA, can act as a tumour suppressor to regulate the progression of various tumours by inhibiting the expression of its target genes. However, whether RGS16 can promote the progression of glioma and whether it is regulated by miR let-7c-5p are still unknown. Here, we confirmed that RGS16 is upregulated in glioma tissues and that high expression of RGS16 is associated with poor survival. Ectopic deletion of RGS16 significantly suppressed glioma cell proliferation and migration both in vitro and in vivo. Moreover, RGS16 was validated as a direct target gene of miR let-7c-5p. The overexpression of miR let-7c-5p obviously downregulated the expression of RGS16, and knocking down miR let-7c-5p had the opposite effect. Thus, we suggest that the suppression of RGS16 by miR let-7c-5p can promote glioma progression and may serve as a potential prognostic biomarker and therapeutic target in glioma.
Humans ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; MicroRNAs/metabolism* ; Glioma/genetics* ; Genes, Tumor Suppressor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Line, Tumor