Asymmetric Total Synthesis of Lancifodilactone G Acetate. 1. Diastereoselective Synthesis of CDEFGH Ring System.

The stereoselective construction of the CDEFGH ring system of lancifodilactone G is described. The key steps in this synthesis are (i) ring-closing metathesis for formation of the oxa-bridged eight-membered ring; (ii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; and (iii) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202412000-00032/figure1/v/2024-04-08T165401Z/r/image-tiff For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Modular Synthesis of Enantioenriched α-Chiral Homoallylic Amidines Enabled by Relay Ir/Cu Catalysis.

The cascade of Ir-catalyzed enantioselective allylic amination and Cu-catalyzed alkyne-azide cycloaddition was designed for the asymmetric synthesis of homoallylic amidines. The nucleophilic addition of an in situ-generated enantioenriched tertiary allylamine to a ketenimine intermediate triggers a rapid and stereospecific zwitterionic aza-Claisen rearrangement in a 1,3-chiral transfer manner. The approach allows modular access to enantioenriched α-chiral homoallylic amidines in high yields with a high level of enantiomeric purity.

Surgical intervention combined with weight-bearing walking training improves neurological recoveries in 320 patients with clinically complete spinal cord injury: a prospective self-controlled study.

Although a large number of trials in the SCI field have been conducted, few proven gains have been realized for patients. In the present study, we determined the efficacy of a novel combination treatment involving surgical intervention and long-term weight-bearing walking training in spinal cord injury (SCI) subjects clinically diagnosed as complete or American Spinal Injury Association Impairment Scale (AIS) Class A (AIS-A). A total of 320 clinically complete SCI subjects (271 male and 49 female), aged 16-60 years, received early (≤ 7 days, n = 201) or delayed (8-30 days, n = 119) surgical interventions to reduce intraspinal or intramedullary pressure. Fifteen days post-surgery, all subjects received a weight-bearing walking training with the "Kunming Locomotion Training Program (KLTP)" for a duration of 6 months. The neurological deficit and recovery were assessed using the AIS scale and a 10-point Kunming Locomotor Scale (KLS). We found that surgical intervention significantly improved AIS scores measured at 15 days post-surgery as compared to the pre-surgery baseline scores. Significant improvement of AIS scores was detected at 3 and 6 months and the KLS further showed significant improvements between all pair-wise comparisons of time points of 15 days, 3 or 6 months indicating continued improvement in walking scores during the 6-month period. In conclusion, combining surgical intervention within 1 month post-injury and weight-bearing locomotor training promoted continued and statistically significant neurological recoveries in subjects with clinically complete SCI, which generally shows little clinical recovery within the first year after injury and most are permanently disabled. This study was approved by the Science and Research Committee of Kunming General Hospital of PLA and Kunming Tongren Hospital, China and registered at ClinicalTrials.gov (Identifier: NCT04034108) on July 26, 2019.

[Dedifferentiation of mammalian neural cells and its induction].

Dedifferentiation of cells has elicited a great deal of attention in the field of cell biology. A great quantity of studies have proved that many types of cells, such as neuron, Schwann cell, astrocyte, oligodendrocyte, etc., within mammalian nervous system could dedifferentiate in different extent, featured in cell becoming immature, reentering cell cycle and regaining pluripotential. This review concerns on dedifferentiation of various types of cells within mammalian nervous system and inducing conditions, as well as its effect on neural regeneration.

Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

BACKGROUND: The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. OBJECTIVES: To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. METHODS: 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes (rs2069762/-330 G/T of IL-2, rs2430561/+874A>T of IFN-γ, rs1800896/-1082G>A and rs1800872/-592C>A of IL-10 and rs2243250/-589C>T of IL-4) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene-gene interactions were assessed using the multifactor-dimensionality reduction method. RESULTS: Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874 AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874 AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05). CONCLUSIONS: Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10--592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection.

Positive effects of bFGF modified rat amniotic epithelial cells transplantation on transected rat optic nerve.

PURPOSE: Effective therapy for visual loss caused by optic nerve injury or diseases has not been achieved even though the optic nerve has the regeneration potential after injury. This study was designed to modify amniotic epithelial cells (AECs) with basic fibroblast growth factor (bFGF) gene, preliminarily investigating its effect on transected optic nerve. METHODS: A human bFGF gene segment was delivered into rat AECs (AECs/hbFGF) by lentiviral vector, and the gene expression was examined by RT-PCR and ELISA. The AECs/hbFGF and untransfected rat AECs were transplanted into the transected site of the rat optic nerve. At 28 days post transplantation, the survival and migration of the transplanted cells was observed by tracking labeled cells; meanwhile retinal ganglion cells (RGCs) were observed and counted by employing biotin dextran amine (BDA) and Nissl staining. Furthermore, the expression of growth associated protein 43 (GAP-43) within the injury site was examined with immunohistochemical staining. RESULTS: The AECs/hbFGF was proven to express bFGF gene and secrete bFGF peptide. Both AECs/hbFGF and AECs could survive and migrate after transplantation. RGCs counting implicated that RGCs numbers of the cell transplantation groups were significantly higher than that of the control group, and the AECs/hbFGF group was significantly higher than that of the AECs group. Moreover GAP-43 integral optical density value in the control group was significantly lower than that of the cell transplantation groups, and the value in the AECs/hbFGF group was significantly higher than that of the AECs group. CONCLUSIONS: AECs modified with bFGF could reduce RGCs loss and promote expression of GAP-43 in the rat optic nerve transected model, facilitating the process of neural restoration following injury.

[Association of genetic polymorphisms of key molecules in JAK/STAT signaling pathway with susceptibility of hepatocellular carcinoma].

OBJECTIVE: To elucidate the association of genetic polymorphisms of key molecules in JAK/STAT signaling pathway with susceptibility of hepatocellular carcinoma (HCC). METHODS: A total of 367 HCC patients and 367 healthy controls were recruited in this sex- and age-matched case-control study. Genetic polymorphisms of IL-6 (rs1800796, -572C > G), STAT3 (rs744166, +26312T > C; rs3816769, +42240T > C; rs6503695, +40980T > C), EGFR (rs11543848, +142530A > G), and mTOR (rs7211818, +170278A > G; rs9674559, +196983A > G; rs11653499, +65678G > A) were genotyped using a mass spectrometry method. Odds ratio (OR) and 95% confidence interval (CI) were calculated. RESULTS: Genotype frequency of the 8 polymorphisms of IL-6, STAT3, EGFR, and mTOR were not significantly different between the patients with HCC and the controls. When stratified by sex, the female subjects who carried STAT3 +26312CC, +42240CC, or +40980CC had a decreased risk of HCC when compared to those who carried TT allele (OR = 0.192, 95%CI: 0.047 - 0.784; OR = 0.180, 95%CI: 0.045 - 0.725; OR = 0.198, 95%CI: 0.049 - 0.806, respectively). When compared with AA genotype on the site of EGFR +142530, the (AG + GG) genotype reduced the risk of HCC in women (OR = 0.422, 95%CI: 0.179 - 0.994). CONCLUSION: The polymorphisms of IL-6 (rs1800796) and mTOR (rs7211818, rs9674559, and rs11653499) were not associated with the HCC susceptibility. Those carrying CC allele in three loci (rs744166, rs3816769, and rs6503695) of STAT3 and (AG + GG) in rs11543848 of EGFR had a decreased risk of HCC in women. However, these results need to be validated using larger sample size.

A novel first aid stretcher for immobilization and transportation of spine injured patients.

Effective immobilization and transportation are vital to the life-saving acute medical care needed when treating critically injured people. However, the most common types of stretchers used today are wrought with problems that can lead to further medical complications, difficulty in employment and rescue, and ineffective transitions to hospital treatment. Here we report a novel first aid stretcher called the "emergency carpet", which solves these problems with a unique design for spine injured patients. Polyurethane composite material, obtained by a novel process of manually mixing isocyanate and additives, can be poured into a specially designed fabric bag and allowed to harden to form a rigid human-shaped stretcher. The effectiveness of the emergency carpet was examined in the pre-hospital management of victims with spinal fractures. Additionally, it was tested on flat ground and complex terrain as well as in the sea and air. We demonstrated that the emergency carpet can be assembled and solidified on the scene in 5 minutes, providing effective immobilization to the entire injured body. With the protection of the emergency carpet, none of the 20 patients, who were finally confirmed to have spinal column fracture or dislocation, had any neurological deterioration during transportation. Furthermore, the carpet can be handled and transported by multiple means under differing conditions, without compromising immobilization. Finally, the emergency carpet allows the critically injured patient to receive multiple examinations such as X-ray, CT, and MRI without being removed from the carpet. Our results demonstrate that the emergency carpet has ideal capabilities for immobilization, extrication, and transportation of the spine injured patients. Compared with other stretchers, it allows for better mobility, effective immobilization, remarkable conformity to the body, and various means for transportation. The emergency carpet is promising for its intrinsic advantages in the pre-hospital management of accident victims.

A meta-analysis of lamivudine for interruption of mother-to-child transmission of hepatitis B virus.

AIM: To determine the therapeutic effect of lamivudine in late pregnancy for the interruption of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: Studies were identified by searching available databases up to January 2011. Inclusive criteria were HBV-carrier mothers who had been involved in randomized controlled clinical trials (RCTs) with lamivudine treatment in late pregnancy, and newborns or infants whose serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) or HBV DNA had been documented. The relative risks (RRs) for interruption of MTCT as indicated by HBsAg, HBV DNA or HBeAg of newborns or infants were calculated with 95% confidence interval (CI) to estimate the efficacy of lamivudine treatment. RESULTS: Fifteen RCTs including 1693 HBV-carrier mothers were included in this meta-analysis. The overall RR was 0.43 (95% CI, 0.25-0.76; 8 RCTs; P(heterogeneity) = 0.04) and 0.33 (95% CI, 0.23-0.47; 6 RCTs; P(heterogeneity) = 0.93) indicated by newborn HBsAg or HBV DNA. The RR was 0.33 (95% CI, 0.21-0.50; 6 RCTs; P(heterogeneity) = 0.46) and 0.32 (95% CI, 0.20-0.50; 4 RCTs; P(heterogeneity) = 0.33) indicated by serum HBsAg or HBV DNA of infants 6-12 mo after birth. The RR (lamivudine vs hepatitis B immunoglobulin) was 0.27 (95% CI, 0.16-0.46; 5 RCTs; P(heterogeneity) = 0.94) and 0.24 (95% CI, 0.07-0.79; 3 RCTs; P(heterogeneity) = 0.60) indicated by newborn HBsAg or HBV DNA, respectively. In the mothers with viral load < 106 copies/mL after lamivudine treatment, the efficacy (RR, 95% CI) was 0.33, 0.21-0.53 (5 RCTs; P(heterogeneity) = 0.82) for the interruption of MTCT, however, this value was not significant if maternal viral load was > 106 copies/mL after lamivudine treatment (P = 0.45, 2 RCTs), as indicated by newborn serum HBsAg. The RR (lamivudine initiated from 28 wk of gestation vs control) was 0.34 (95% CI, 0.22-0.52; 7 RCTs; P(heterogeneity) = 0.92) and 0.33 (95% CI, 0.22-0.50; 5 RCTs; P(heterogeneity) = 0.86) indicated by newborn HBsAg or HBV DNA. The incidence of adverse effects of lamivudine was not higher in the mothers than in controls (P = 0.97). Only one study reported side effects of lamivudine in newborns. CONCLUSION: Lamivudine treatment in HBV carrier-mothers from 28 wk of gestation may interrupt MTCT of HBV efficiently. Lamivudine is safe and more efficient than hepatitis B immunoglobulin in interrupting MTCT. HBV MTCT might be interrupted efficiently if maternal viral load is reduced to < 106 copies/mL by lamivudine treatment.

Association of novel mutations and haplotypes in the preS region of hepatitis B virus with hepatocellular carcinoma.

The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (P<0.001), whereas a haplotypic carriage with a single mutation and another three wildtypes were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently.

HBV genotype C is independently associated with cirrhosis in community-based population.

AIM: To determine the association of hepatitis B virus (HBV) genotypes with probable cirrhosis and fatty liver in community-based populations. METHODS: A multi-stage cluster probability sampling method was applied to recruit 10 167 subjects aged between 6 and 72 years from our epidemiological bases in Eastern China. After excluding the subjects co-infected with hepatitis C or hepatitis D viruses, the hepatitis B surface antigen (HBsAg)-positive subjects were examined for HBV genotype, serum viral load, alanine aminotransferase (ALT), hepatitis B e antigen (HBeAg) status, and ultrasonographic changes. Logistic regression models were used to determine the factors associated with probable cirrhosis and fatty liver. RESULTS: Of 634 HBsAg-positive subjects with HBV genotype determined, 82 had probable cirrhosis (ultrasonographic score > or = 5), 42 had ultrasonographic fatty liver. Probable cirrhosis was only found in the HBeAg-negative subjects, and more frequently found in the subjects with genotype C than in those with genotype B (14.8% vs 8.0%, P = 0.018). In HBeAg-negative subjects, high viral load was frequently associated with abnormal ALT level, while ALT abnormality was more frequent in those with probable cirrhosis than those without (19.5% vs 7.8%, P = 0.001). Univariate analysis showed that age, sex, HBV genotypes, and viral load were not significantly associated with ultrasonographic fatty liver, whereas ALT abnormality was significantly related to ultrasonographic fatty liver (OR = 4.54, 95% CI: 2.11-9.75, P < 0.001). Multivariate analysis demonstrated that HBV genotype C, age (> or = 45 years), male sex, and ALT abnormality were independently associated with probable cirrhosis (AOR = 2.30, 95% CI: 1.26-4.19; AOR = 1.81, 95% CI: 1.10-2.99; AOR = 1.74, 95% CI: 1.03-2.95; AOR = 2.98, 95% CI: 1.48-5.99, respectively). CONCLUSION: A crude prevalence of probable cirrhosis is 12.9% in the community-based HBV-infected subjects. HBV genotype C is independently associated with probable cirrhosis in the HBeAg-negative subjects.