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Background: Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations., Methods: We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients' iPSCs., Results: The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines., Conclusions: MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS., Methods: We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors., Results: The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17-49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46-63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS., Conclusions: Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression., (Copyright © 2021 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism (SNP) rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS (SALS) in a large Chinese cohort., Methods: To assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing., Results: The allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance (P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15)., Conclusions: The SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future.

Background: The spectrum of abnormal behaviors in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) has been described, but its practical meaning, namely its impact on caregiver burden, has not been clearly documented in Chinese population. This study aimed to assess the distribution of abnormal behaviors in Chinese population, and to analyze the relationship between behavior changes and caregiver burden., Methods: Sixty-five patients with ALS/MND have been consecutively enrolled into registry platform of Peking Union Medical College Hospital. An investigation was performed to these patients and their caregivers using the revised ALS function rating scale, Frontal Behavioral Inventory-ALS version, the Frontal Assessment Battery, and the Caregiver Burden Inventory., Results: Twenty-eight (43.1%) patients displayed abnormal behaviors of varying degrees, with one fulfilling the diagnostic criteria of frontotemporal lobe degeneration. Irritability, logopenia, and inflexibility ranked top 3 of abnormal behavior list. Correlation analysis revealed that the degree of behavioral change and frontal cognitive status were significantly associated with caregiver burden, with more extensive impact from disinhibitive behaviors. Analysis of covariance analysis showed that after associated factors were corrected, caregivers of patients with moderate to severe behavior change reported significantly heavier developmental burden, physical burden, and total burden than those with no behavioral change., Conclusions: Neurobehavioral symptoms could present in around 40% of Chinese patients with ALS/MND, and the distribution of these behaviors was also unique. Besides, abnormal behaviors were highly related to caregivers' burden.

Background: Shikonin is a major active chemical component extracted from Lithospermi Radix, an effective traditional herb in various types of wound healing. Shikonin can accelerate granulomatous tissue formation by the rat cotton pellet method and induce neovascularization in granulomatous tissue. The purpose of the study was to investigate its mechanism of action in human skin cells., Methods: MTS assay was used to measure cell growth. The collagen type I (COL1 ) mRNA expression and procollagen type I C-peptide (PIP) production were detected by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Immunofluorescence and western blot analyses were carried out to investigate nuclear factor-κB (NF-κB) signaling pathway. Cell-based proteasome activity assay was used to determine proteasome activity., Results: In this study, we found that 10 μmol/L shikonin stimulated the growth of normal human keratinocytes and 1 μmol/L shikonin promoted growth of human dermal fibroblasts. However, shikonin did not directly induce COL1 mRNA expression and PIP production in dermal fibroblasts in vitro. In addition, 1 μmol/L shikonin inhibited translocation of NF-κB p65 from cytoplasm to nucleus induced by tumor necrosis factor-α stimulation in dermal fibroblasts. Furthermore, shikonin inhibited chymotrypsin-like activity of proteasome and was associated with accumulation of phosphorylated inhibitor κB-α in dermal fibroblasts., Conclusions: These results suggested that shikonin may promote wound healing via its cell growth promoting activity and suppress skin inflammation via inhibitory activity on proteasome. Thus, shikonin may be a potential therapeutic reagent both in wound healing and inflammatory skin diseases.

Background: Dysfunctional spinal circuit may play a role in the pathophysiology of amyotrophic lateral sclerosis (ALS). The purpose of this study was to use F waves for assessment of segmental motoneuronal excitability following upper motor neuron (UMN) dysfunctions in ALS., Methods: We studied the F waves of 152 ulnar nerves recorded from abductor digiti minimi in 82 patients with ALS. Two groups of hands were defined based on the presence or absence of pyramidal signs in the same upper limb. The group with pyramidal signs in the upper limbs was designated as the P group, and the group without pyramidal signs in the upper limbs was designated as the NP group., Results: The mean (P < 0.001), median (P < 0.001) and maximum (P = 0.035) F wave amplitudes, mean (P < 0.001), median (P < 0.001) and maximum (P = 0.003) F/M amplitude ratio, index repeating neuron (P < 0.001) and index repeater F waves (P < 0.001) of the P group were significantly increased compared with the NP group. No significant differences were identified for F wave chronodispersion (P = 0.628), mean F wave latency (P = 0.151), minimum F wave latency (P = 0.211), maximum F wave latency (P = 0.199), F wave persistence (P = 0.738), F wave duration (P = 0.152), F wave conduction velocity (P = 0.813) and number of giant F waves (P = 0.072) between the two groups., Conclusions: In this study, increased F wave amplitude, F/M amplitude ratio and number of repeater F waves reflected enhanced segmental motoneuronal excitability following UMN dysfunctions in ALS.

Background: Although many midterm oncologic data have been reported for extraperitoneal laparoscopic radical prostatectomy (ELRP) in western countries, few oncologic data of the extraperitoneal procedure was published in China. The aim of the study was to evaluate the oncologic outcomes of patients treated with ELRP in China., Methods: From January 2005 to March 2010, a total of 152 consecutive patients diagnosed with clinically localized prostate cancer were included in this study and treated with ELRP. The patients were staged according to the TNM (tumor, nodes, metastases) system. Median and mean postoperative follow-up were 28.1 months and 27.0 months, respectively. The patients were retrospectively analyzed for progression-free survival., Results: One hundred and twelve cases (73.7%) were postoperatively diagnosed as pT2 in, and 40 cases (26.3%) as pT3. Positive lymph nodes were shown in 5 patients (3.3%). Gleason score was < 7 in 49 men (32.2%), 7 in 69 men (45.4%), and > 7 in 34 men (22.4%). Positive surgical margins (PSM) were observed in 15 patients (9.9%), which included 32.0% of all pT3a cases and 46.7% of all pT3b cases, respectively. The overall prostate-specific antigen recurrence-free survival rate was 86% in all patients. The recurrence-free survival rates were 91.8% and 62.2% in pT2N0 patients and pT3N0 patients, respectively. Preoperative prostate-specific antigen, surgical margins, tumor stage, and lymph nodal status were identified as independent predictors of biochemical recurrence-free survival using multivariate Cox proportional hazard model., Conclusions: ELRP is a precise, safe and effective procedure at this particular Chinese institution. The prognostic power of prostate-specific antigen relapse after ELRP is not identical to that described previously with transperitoneal or open retropubic approaches.

Ectopic Cushing’s syndrome caused by pheochromocytoma is rare. We reported a 15-year-old female patient who was admitted to hospital with typical Cushing’s syndrome. She had not started menstruation. Her plasma adrenocorticotropic hormone (ACTH) and 24-hour urinary free cortisol levels were extremely high. Gonadal and progestational hormone levels were also abnormal. Abdominal computed tomography scans and enhanced scans revealed multiple irregular tumors in the right adrenal. Pelvic echogram showed an infantile uterus, while the ovaries were at an immature stage of development. Retroperitoneal laparoscopic right adrenalectomy was performed without intraoperative complications. Histology and immunohistochemistry of the tumor were consistent with pheochromocytoma. Retroperitoneal laparoscopic adrenalectomy is a safe procedure with satisfactory outcomes and allows for rapid recovery.

Background: Hemorrhagic fever with renal syndrome (HFRS) is endemic in Junan county, Shandong Province, China. We conducted geographic information system (GIS)-based spatial analysis with the objective of estimating the spatial distribution of rodent populations and their hantavirus infection patterns, to describe the spatial relationships of hantavirus strains in small ecological areas and to identify key areas in endemic areas of HFRS for future public health planning and resource allocation., Methods: Rodent sampling was conducted in seven villages in Junan county from February 2006 to January 2007 using field epidemiological surveillance. Dynamics of hantavirus infection and population densities in rodents were investigated. Spatial statistical techniques including Ripley' L index and nearest neighbour hierarchical (NNH) clustering analysis were conducted to reveal the spatial structure of rodent populations in seven villages. Phylogenetic analysis and two-dimensional minimal spanning tree (2-D MST) models were employed to describe the spatial relationship of hantavirus strains., Results: Data showed that Mus musculus was the most common species in our study area, followed by Rattus norvegicus. Ripley's L index and NNH analysis showed that the spatial distribution of all captured rodents, Mus musculus and Rattus norvegicus in seven villages were clustered and there were hotspot areas of rodent distribution. The branches of 2-D MSTs had similar topologies to those of corresponding phylogenetic trees, and hantavirus strains exhibited obvious connective traces in seven villages., Conclusions: These results contribute to the understanding of the spatial distribution of rodent populations and hantavirus infection patterns in small areas, and identify priority areas within the epidemic areas for the development of a better prevention strategy against hemorrhagic fever with renal syndrome in a small ecological area.

Background: Breast conserving surgery (BCS) has been the standard surgical procedure for the treatment of early breast cancer. Endoscopic subcutaneous mastectomy (ESM) plus immediate reconstruction with implants is an emerging procedure. The objective of this prospective study was to evaluate the clinical outcomes of these two surgical procedures in our clinical setting., Methods: From March 2004 to October 2007, 43 patients with breast cancer underwent ESM plus axillary lymph node dissection and immediate reconstruction with implants, while 54 patients underwent BCS. The clinical and pathological characteristics, surgical safety, and therapeutic effects were compared between the two groups., Results: There were no significant differences in the age, clinical stage, histopathologic type of tumor, operative blood loss, postoperative drainage time, and postoperative complications between the two groups (P > 0.05). The postoperative complications were partial necrosis of the nipple and superficial skin flap in the ESM patients, and hydrops in the axilla and residual cavity in the BCS patients. There was no significant difference in the rate of satisfactory postoperative cosmetic outcomes between the ESM (88.4%, 38/43) and BCS (92.6%, 50/54) patients (P > 0.05). During follow-up of 6 months to 4 years, all patients treated with ESM were disease-free, but 3 patients who underwent BCS had metastasis or recurrence -one of these patients died of multiple organ metastasis., Conclusions: After considering the wide indications for use, high surgical safety, and favorable cosmetic outcomes, we conclude that ESM plus axillary lymph node dissection and immediate reconstruction with implants - the new surgery of choice for breast cancer - warrants serious consideration as the prospective next standard surgical procedure.

Background: Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease characterized by the loss of motor neurons in the spinal cord, brainstem, and cerebral cortex, which results in muscle weakness, atrophy. Sporadic ALS (SALS) accounts for about 90% of ALS cases, but the etiology is largely unknown. Most of the researchers consider it to be a complex disease. There have been several genome-wide association (GWA) studies reporting several single nucleotide polymorphisms (SNPs) which are susceptible to ALS, but no data of Asians (including Chinese) yet. We investigate whether the polymorphism of rs10260404 in DPP6 gene is associated with SALS in Chinese Han origin to compare the ethnic differences between Chinese Han origin and other populations., Methods: The genomic DNA was extracted from the leukocytes of whole blood samples in 58 Chinese Han patients with SALS and 52 healthy controls. The asymmetric PCR was processed in the presence of an unlabeled probe that contained the rs10260404 locus. The product was genotyped on a light scanner using high resolution melting method and some were confirmed with sequencing., Results: The rs10260404 polymorphism was in Hardy-Weinberg equilibrium in patients and controls. The CC genotype and the C allele were similar in patients compared with healthy subjects and not associated with an increased risk of Chinese SALS patients (chi(2) = 0.29, OR = 1.26, 95% CI 0.55 - 2.87, P > 0.05)., Conclusions: The rs10260404 is not associated with ALS susceptibility in Chinese people with Han origin which may be due to ethnic differences. More study with large number of cases in Chinese population is really necessary.

Background: Podocyte has inflammatory role in the development of diabetic nephropathy (DN). Mycophenolate mofetil (MMF), an anti-inflammatory agent, can suppress macrophage infiltration and reduce renal injury in streptozotocin-induced diabetic rats. Angiotensin II receptor blocker (ARB), another renal protecting agent, can decrease podocyte loss in DN. In this study, we detected the expression levels of monocyte chemoattractant protein-1 (MCP-1) and nephrin to evaluate podocyte's role in inflammatory reaction in DN, observe and compare the effect of MMF alone and in combination with valsartan, on preventing podocyte loss in streptozotocin (STZ) induced diabetic rats., Methods: Diabetic model was constructed in uninephrectomized male Wistar rats by single peritoneal injection of STZ (65 mg/kg). The successfully induced diabetic rats were randomly divided into four groups: diabetes without treatment group (DM), valsartan treated group (DMV), MMF treated group (DMM), and combined therapy group (DMVM). Normal rats of the same sibling were chosen as control (NC). At the end of the 8th week, serum biochemistry, 24-hour urinary protein (UP) and the ratio of kidney weight/body weight (RWK/B) were measured. The rats were sacrificed for the observation of renal histomorphology through light and electron microscope. Nephrin, desmin and MCP-1 levels were detected by semi-quantitative immunohistochemical assays. Real-time quantitative PCR was used to detect the mRNA levels of nephrin and MCP-1., Results: Compared with group NC, serum glucose level, 24-hour UP and RWK/B in group DM were significantly higher (P < 0.01), and the nephrin mRNA level in DM group was significantly lower (P < 0.05). The nephrin mRNA expression levels in group DMV, DMM and DMVM were all higher than that of DM group (P < 0.05) and no significant differences were found among the three treatment groups (P > 0.05). Treatment with MMF, valsartan or their combination could significantly decrease the 24-hour UP and RWK/B, and suppress glomerulosclerosis and interstitial fibrotic lesions in diabetic rats. In diabetic rats, the high expressions of desmin and MCP-1 in kidney were suppressed by valsartan, MMF or their combination., Conclusions: Podocytes are involved in the inflammatory reaction of diabetic rats. MMF could suppress MCP-1 and desmin expression, enhance nephrin expression, and attenuate proteinuria in diabetic rats. The combined therapy of valsartan and MMF did not show any superiority over monotherapies on renal protection. MMF may have renoprotective effect in early stages of diabetic nephropathy through preventing podocytes loss and anti-inflammatory activity.

Background: Percutaneous microballoon compression (PMC) for trigeminal neuralgia is an important therapeutic method. The aim of this study was to review the effects of PMC for trigeminal neuralgia in 276 patients., Methods: From December 2000 to May 2003, 276 patients with trigeminal neuralgia were treated with PMC. The course of the disease ranged from 3 months to 38 years. Under the guidance of C-arm X-ray, 14# needle was placed into the foramen ovale using the classical Hakanson's technique. Fogarty balloon catheter was navigated into the Meckel's cave tenderly. A small amount of Omnipaque was slowly injected to inflate the balloon and compress the trigeminal ganglion for 3 to 10 minutes., Results: A total of 290 PMC were performed on the 276 patients. Among them, 252 had immediate relief from pain. The patients were followed up for a mean of 18.7 months (range, 4 to 32), 14 of them had a recurrence. Of the 14 patients, 12 were re-operated with PMC, and the pain was all controlled successfully., Conclusions: PMC is an effective and technically simple method for trigeminal neuralgia. For older patients with trigeminal neuralgia, it may be the first choice.