Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression ...Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis(RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA(STR/Ort)mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OAassociated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.展开更多
Background: Domestic violence is a pattern of assault and behavior perpetrated by one partner against the other. Historically most of those oppressed by domestic violence have been women. The lifetime prevalence of do...Background: Domestic violence is a pattern of assault and behavior perpetrated by one partner against the other. Historically most of those oppressed by domestic violence have been women. The lifetime prevalence of domestic violence against women is 10% - 69%. Though this violence might have started or escalated during pregnancy, pregnancy specific prevalence is between 1% - 20%. The objective was to determine the prevalence and obstetric complications. Domestic violence is against pregnant women in tertiary clinic of a developing nation. Methodology: It was a hospital based cross-sectional case control study conducted within the period of one year. Close ended questionnaires were administered. Result: Two hundred and seventy patients were recruited. The lifetime prevalence of physical violence against women was 28.5%. 12.5% (5/40) of victims smoke cigarettes;the prevalence of alcohol intake by the victims was 45%. 72.5% of partners of victims smoke as compared to 25.5% of partners of non victims. Unemployed women were victims of domestic violence far more than the employed women. Pregnant women who are victims of physical violence are more likely to suffer adverse pregnancy outcome. Violence in pregnancy is quite commoner than most of the conditions routinely screened for during antenatal care. The association of such violence with significant maternal and fetal/neonatal morbidity and mortality emphasizes the fact that domestic violence is not just a social problem but a feto-maternal health hazard that requires the input of every stakeholder to address.展开更多
AIM:To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy(PDT) among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selay...AIM:To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy(PDT) among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014.METHODS:Study subjects were recruited retrospectively using the Electronic Medical Record(EMR) database software in Hospital Selayang.Demographic data,medical history,diagnostic procedure,treatments and diagnosis of patients were recorded.RESULTS:The five-year analysis included 821 patients with a mean age of 65.9±11.73 y.Overall,there were a highernumber of males(63.1%) and a higher number of Chinese(47.4%) patients.Among the 821 patients,62.9% received ranibizumab injection followed by 19.2% PDT therapy and 17.9% had ranibizumab combined with PDT therapy.Age-related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV) were the most common retinal eye diseases reported,recording prevalence of 25.0% and 45.6%,respectively.The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014.In terms of treatment,following multiple logistic regression,AMD was associated with the subjects being more likely to have received ranibizumab monotherapy(P〈0.001) while PCV was associated with more likely to have received PDT(P〈0.001) and PDT combined with ranibizumab therapy(P〈0.001).CONCLUSION:The tertiary care setting in Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD,while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.展开更多
A 30 years old grandmultiparous woman presented with 6 month history of severe abdominal pain and 4 month history of progressive abdominal swelling associated with multiple swellings on her abdomen and her breasts. Sh...A 30 years old grandmultiparous woman presented with 6 month history of severe abdominal pain and 4 month history of progressive abdominal swelling associated with multiple swellings on her abdomen and her breasts. She had laparotomy two years earlier for a suspected fibroid. A repeat laparatomy discovered a huge left ovarian tumour;which are multilobulated and hard. She had Total Abdominal Hysterectomy and Salpingectomy with Lumpectomy on both breast. Histology report turned out as Dysgerminoma, breast, Subcutaneous Tissue and Skin Metastatic Dysgerminoma.展开更多
Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an ox...Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.展开更多
Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechani...Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechanism of action using molecular modeling. Methods: Three different human carcinoma cell lines were used namely hepatocyte carcinoma (HEPG2), breast adenocarcinoma (MCF7) and colon cancer (HCT116). Molecular docking simulations for tested thiazole analogue and its virtual analogues against the cytochrome P-450 2A6 enzyme and mutated SOD were performed. Results: Cell lines cytotoxicity revealed that the tested thiazole analogue exerts a significant anti-proliferative activity in all the used human carcinoma cell lines with a pronounced anti-proliferative effect in liver carcinoma cell line HEPG2 (IC50 = 23.8 μg/ml) whereas the anti-proliferative effect in colon carcinoma and breast cancer cell lines was poor with IC50 = 50 μg/ml and IC50 > 50 μg/ml respectively. The postulated mechanism of action revealed the high affinity to inhibit SOD and CYP2A6 enzymes in the liver. Conclusion: The thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl)thiazole) is a potential liver specific anticancer agent capable of interfering with both apoptotic signaling pathway and the free radical processing in liver which leads to more studies on liver cancer from different perspective rather than the apoptotic signaling pathway.展开更多
Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period.To address this issue,this study introduces a hydrogel that creates a r...Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period.To address this issue,this study introduces a hydrogel that creates a rejuvenating microenvironment,thereby facilitating efficient bone repair during the initial two weeks following bone defect surgery.The hydrogel,named GelHFS,was created through host-guest polymerization of gelatin and acrylatedβ-cyclodextrin.Incorporation of the human fetal mesenchymal stem cell secretome(HFS)formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell niche.Our results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrinβ1-induced focal adhesion pathway.Implantation of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrinβ1-expressing cells and enhanced new bone formation and bone strength.Our findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone defect.These findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.展开更多
To compare the surgical managements for ectopic pregnancy Methods In a retrospective analysis, we examined the trend of surgical procedures and the results of different management in 149 patients Results The chan...To compare the surgical managements for ectopic pregnancy Methods In a retrospective analysis, we examined the trend of surgical procedures and the results of different management in 149 patients Results The change from laparotomy to laparoscopic treatment was significant The success rates of salpingostomy and salpingectomy under laparoscopy or laparotomy were 100% No serious complications occurred The operation time and length of hospital stay for laparoscopic salpingostomy were shorter than those for laparotomy with salpingostomy Conclusion Laparoscopic salpingostomy and laparoscopic salpingectomy are better than laparotomy in the treatment of ectopic pregnancy展开更多
Background Recent studies showed that bone marrow-derived mesenchymal stem ceils (BMSCs) had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 ...Background Recent studies showed that bone marrow-derived mesenchymal stem ceils (BMSCs) had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 (GDF-6) on the tenogenic differentiation of BMSCs in vitro, and then combined with small intestine submucous (SIS) to promote tendon regeneration in vivo. Methods The BMSCs were isolated from the green fluorescent protein (GFP) rats, and were characterized by multi-differentiation assays following our previous study protocol. BMSCs cultured with different concentrations of GDF-6, without growth factors served as control. After 2 weeks, mRNA expression and protein expression of tendon specific markers were examined by qRT-PCR and Western blotting to define an optimal concentration of GDF-6. Mann-Whitney U-test was used to compare the difference in relative mRNA expression among all groups; P 〈0.05 was regarded as statistically significant. The GDF-6 treated BMSCs combined with SIS were implanted in nude mice and SD rat acute patellar tendon injury model, the BMSCs combined with SIS served as control. After 12 and 4 weeks in nude mice and tendon injury model, the samples were collected for histology. Results After the BMSCs were treated with different concentration of GDF-6 for 2 weeks, the fold changes of the specific markers (Tenomodulin and Scleraxis) mRNA expression were significantly higher in GDF-6 (20 ng/ml) group (P 〈_0.05), which was also confirmed by Western blotting result. The BMSCs became parallel in orientation after GDF-6 (20 ng/ml) treatment, but the BMSCs in control group were randomly oriented. The GDF-6 (20 ng/ml) treated BMSCs were combined with SIS, and were implanted in nude mice for 12 weeks, the histology showed neo-tendon formation. In the SD rat patellar tendon window injury model, the histology also indicated the GDF-6 (20 ng/ml) treated BMSCs combined with SIS could promote tendon regeneration. Conclusions GDF-6 has tenogenic effect on the tenogenic differentiation of BMSCs, and GDF-6 (20 ng/ml) has better tenogenic effect compared to other concentrations. The GDF-6 (20 ng/ml) treated BMSCs combined with SIS can form neo-tendons and promote tendon regeneration.展开更多
In the current global crisis of antibiotic resistance,delivery systems are emerging to combat resistant bacteria in a more efficient manner.Despite the significant advances of antibiotic nanocarriers,many challenges l...In the current global crisis of antibiotic resistance,delivery systems are emerging to combat resistant bacteria in a more efficient manner.Despite the significant advances of antibiotic nanocarriers,many challenges like poor biocompatibility,premature drug release,suboptimal targeting to infection sites and short blood circulation time are still challenging.To achieve targeted drug delivery and enhance antibacterial activity,here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin(PEG-Schiff-Van)prodrug and free Van in one drug delivery system.The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition.Notably,on account of the combination of physical encapsulation and chemical conjugation of vancomycin,these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior,which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period.In addition,more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity.Using this strategy,this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites,thereby presenting prominent antibacterial therapy both in vitro and in vivo.This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles,which would be a promising class of antimicrobial materials for potential clinical translation.展开更多
Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 i...Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.展开更多
Purpose: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (A RMD) over 1 year. Methods: The consecutive interventional c...Purpose: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (A RMD) over 1 year. Methods: The consecutive interventional case series included 5 6 patients with exudative ARMD. During vitrectomy the submacular neovascular mem brane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy, w ere injected into the submacular space. Included were patients with subfoveal oc cult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a pigme nt epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes). Outcome me asures were visual acuity, foveal fixation, size of CNV and rate of recurrence b ased on fluorescence angiographic imaging. Results: All patients underwent succe ssful surgical removal of the CNV with consecutive subretinal IPE injection. Vis ual acuity was better than 20/100 in 19 patients preoperatively and in 18 patien ts postoperatively. A visual acuity of 20/100 or less was found in 37 patients p reoperatively and in 38 patients postoperatively. Mean preoperative visual acuit y (1.0±0.3 logMAR units) did not change significantly after 1 year (1.0±0.3 lo gMAR units). Ten eyes (18%) developed a recurrence. Fixation within the surgica lly denuded area could be demonstrated in 25 eyes (45%). Conclusions: Autologou s IPE translocation for ARMD over one year can preserve foveal function on a low level, but cannot improve visual acuity. IPE translocation is technically feasi ble with a low rate of complications. Continued research seems justified to impr ove functional outcome.展开更多
Aims: To determine whether central corneal thickness (CCT) is a significant pr edictor of visual field and optic disc progression in open angle glaucoma. Metho ds: Data were obtained from a prospective study of glauco...Aims: To determine whether central corneal thickness (CCT) is a significant pr edictor of visual field and optic disc progression in open angle glaucoma. Metho ds: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 month s. Progression was determined using a trend based approach called evidence of ch ange (EOC) analysis in which sectoral ordinal scores based on the significance o f regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using t he event based glaucoma change probability (GCP) analysis using both total and p attern deviation. Results: The sample contained 101 eyes of 54 patients (mean (S D) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseli ne visual fields and lower mean IOP in the follow up. In the longitudinal analys is CCT was not correlated with the EOC scores for visual field or optic disc cha nge. In the GCP analyses, there was a tendency for groups classified as progress ing to have lower CCT compared to nonprogressing groups. In a multivariate analy ses accounting for IOP, the opposite was found, whereby higher CCT was associate d with visual field progression. None of the independent factors were predictive of optic disc progression. Conclusions: In this cohort of patients with establi shed glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.展开更多
Background Reports of applying cervical pedicle screw (CPS) system in the posterior cervical spine surgeries are limited because of its inherent risk of neurovascular injury. The clinical results of cervical spine i...Background Reports of applying cervical pedicle screw (CPS) system in the posterior cervical spine surgeries are limited because of its inherent risk of neurovascular injury. The clinical results of cervical spine instability treated with CPS system were retrospectively analyzed, and the clinical efficacy and safety of this management were evaluated. Methods Twenty-five patients with cervical spine instability undergoing posterior C3-C7 single/double door laminoplasty and free-hand CPS fixation as well as graft fusion were investigated; of whom, 3 were due to trauma, and 22 degenerative cervical pathogenesis. One hundred and fifty in total, CPSs were implanted in 5 cervical segments for 1 patient, 4 for 2, 3 for 18, and 2 for 4. Japanese Orthopaedic Association (JOA) score and its improvement rate, neck disability index (NDI), segmental stability, pedicle cortex perforation rate and other complication-associated parameters were assessed. Results The average follow-up was 16.6 (6-30) months. Compared with pre-operative values, JOA score improved by 4.10±0.84 points on average (P 〈0.05) at 6 months post operation, with a mean improvement rate of 61%. While the pre-operative and 6-month post-operative NDI were 32.96_-'_-~.13 and 16.84_+4.40 (P 〈0.05), respectively. At 6-month post-operation and the final follow-up, fused segments were stable. Pedicle cortex perforation rate was 8.0%, with no neurovascular complications observed. Conclusions Anatomizing the pre-operative radiographic data facilitates the precise operative design prior to surgery; and CPS system is capable of offering safe and satisfying outcomes in the management of cervical spine instability.展开更多
Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study ai...Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes ofrituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number ofrituximab treatment cycles, and OS was only associated with age 〉60 years (P 〈 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.展开更多
基金supported by the NIH/NIAMS grants AR071432 and AR063943 (to X.C.)
文摘Osteoarthritis(OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective diseasemodifying therapy. Here, we report that elevated cyclooxygenase-2(COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis(RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA(STR/Ort)mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OAassociated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.
文摘Background: Domestic violence is a pattern of assault and behavior perpetrated by one partner against the other. Historically most of those oppressed by domestic violence have been women. The lifetime prevalence of domestic violence against women is 10% - 69%. Though this violence might have started or escalated during pregnancy, pregnancy specific prevalence is between 1% - 20%. The objective was to determine the prevalence and obstetric complications. Domestic violence is against pregnant women in tertiary clinic of a developing nation. Methodology: It was a hospital based cross-sectional case control study conducted within the period of one year. Close ended questionnaires were administered. Result: Two hundred and seventy patients were recruited. The lifetime prevalence of physical violence against women was 28.5%. 12.5% (5/40) of victims smoke cigarettes;the prevalence of alcohol intake by the victims was 45%. 72.5% of partners of victims smoke as compared to 25.5% of partners of non victims. Unemployed women were victims of domestic violence far more than the employed women. Pregnant women who are victims of physical violence are more likely to suffer adverse pregnancy outcome. Violence in pregnancy is quite commoner than most of the conditions routinely screened for during antenatal care. The association of such violence with significant maternal and fetal/neonatal morbidity and mortality emphasizes the fact that domestic violence is not just a social problem but a feto-maternal health hazard that requires the input of every stakeholder to address.
基金Supported by Putra Grant from Universiti Putra Malaysia(No.9409800No.9432700)
文摘AIM:To describe the prevalence and changes in treatment patterns of ranibizumab and photodynamic therapy(PDT) among retinal disease patients who attended the Ophthalmology Clinic in the tertiary care Hospital Selayang from 2010 to 2014.METHODS:Study subjects were recruited retrospectively using the Electronic Medical Record(EMR) database software in Hospital Selayang.Demographic data,medical history,diagnostic procedure,treatments and diagnosis of patients were recorded.RESULTS:The five-year analysis included 821 patients with a mean age of 65.9±11.73 y.Overall,there were a highernumber of males(63.1%) and a higher number of Chinese(47.4%) patients.Among the 821 patients,62.9% received ranibizumab injection followed by 19.2% PDT therapy and 17.9% had ranibizumab combined with PDT therapy.Age-related macular degeneration(AMD) and polypoidal choroidal vasculopathy(PCV) were the most common retinal eye diseases reported,recording prevalence of 25.0% and 45.6%,respectively.The trend in ranibizumab treatment was reported to increase while PDT showed a decrease in trend from year 2010 to 2014.In terms of treatment,following multiple logistic regression,AMD was associated with the subjects being more likely to have received ranibizumab monotherapy(P〈0.001) while PCV was associated with more likely to have received PDT(P〈0.001) and PDT combined with ranibizumab therapy(P〈0.001).CONCLUSION:The tertiary care setting in Malaysia is consistent with management of patients from other countries whereby ranibizumab is the most common treatment given to patients with AMD,while PCV patients most commonly receive PDT and ranibizumab combined with PDT therapy.
文摘A 30 years old grandmultiparous woman presented with 6 month history of severe abdominal pain and 4 month history of progressive abdominal swelling associated with multiple swellings on her abdomen and her breasts. She had laparotomy two years earlier for a suspected fibroid. A repeat laparatomy discovered a huge left ovarian tumour;which are multilobulated and hard. She had Total Abdominal Hysterectomy and Salpingectomy with Lumpectomy on both breast. Histology report turned out as Dysgerminoma, breast, Subcutaneous Tissue and Skin Metastatic Dysgerminoma.
文摘Oxidative stress is one of the main mechanisms responsible for male infertility.Various conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the reproductiveenvironment.Spermatozoa are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe egg.Excessive reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive success.This double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on treatment.Sperm concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this parameter.In conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.
文摘Purpose: Aim of this study is to assess the anti-proliferative effect of the thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl) thiazole) with different human carcinoma cell lines and to postulate its possible mechanism of action using molecular modeling. Methods: Three different human carcinoma cell lines were used namely hepatocyte carcinoma (HEPG2), breast adenocarcinoma (MCF7) and colon cancer (HCT116). Molecular docking simulations for tested thiazole analogue and its virtual analogues against the cytochrome P-450 2A6 enzyme and mutated SOD were performed. Results: Cell lines cytotoxicity revealed that the tested thiazole analogue exerts a significant anti-proliferative activity in all the used human carcinoma cell lines with a pronounced anti-proliferative effect in liver carcinoma cell line HEPG2 (IC50 = 23.8 μg/ml) whereas the anti-proliferative effect in colon carcinoma and breast cancer cell lines was poor with IC50 = 50 μg/ml and IC50 > 50 μg/ml respectively. The postulated mechanism of action revealed the high affinity to inhibit SOD and CYP2A6 enzymes in the liver. Conclusion: The thiazole analogue (5-acetyl-4-methyl-2-(3-pyridyl)thiazole) is a potential liver specific anticancer agent capable of interfering with both apoptotic signaling pathway and the free radical processing in liver which leads to more studies on liver cancer from different perspective rather than the apoptotic signaling pathway.
基金National Natural Science Foundation of China(82172430 and 82272505)University Grants Committee,Research Grants Council of the Hong Kong Special Administrative Region,China(14113723,14108720,14121721,14202920,N_CUHK472/22,C7030-18G,T13-402/17-N and AoE/M-402/20)+1 种基金Heath and Medical Research Fund(HMRF)Hong Kong(17180831,08190416 and 09203436)Hong Kong Innovation Technology Commission Funds(PRP/050/19FX),CUHK direct grant(2022.042).
文摘Osteoporotic bone defects pose a significant challenge for bone regeneration as they exhibit impaired healing capacity and delayed healing period.To address this issue,this study introduces a hydrogel that creates a rejuvenating microenvironment,thereby facilitating efficient bone repair during the initial two weeks following bone defect surgery.The hydrogel,named GelHFS,was created through host-guest polymerization of gelatin and acrylatedβ-cyclodextrin.Incorporation of the human fetal mesenchymal stem cell secretome(HFS)formed GelHFS hydrogel aimed at mimicking a rejuvenated stem cell niche.Our results demonstrated that GelHFS hydrogel promotes cell stellate spreading and osteogenic differentiation via integrinβ1-induced focal adhesion pathway.Implantation of GelHFS hydrogel in an osteoporotic bone defect rat model recruited endogenous integrinβ1-expressing cells and enhanced new bone formation and bone strength.Our findings reveal that GelHFS hydrogel provides a rejuvenating niche for endogenous MSCs and enhances bone regeneration in osteoporotic bone defect.These findings highlight the potential of GelHFS hydrogel as an effective therapeutic strategy for addressing challenging bone healing such as osteoporotic bone regeneration.
文摘To compare the surgical managements for ectopic pregnancy Methods In a retrospective analysis, we examined the trend of surgical procedures and the results of different management in 149 patients Results The change from laparotomy to laparoscopic treatment was significant The success rates of salpingostomy and salpingectomy under laparoscopy or laparotomy were 100% No serious complications occurred The operation time and length of hospital stay for laparoscopic salpingostomy were shorter than those for laparotomy with salpingostomy Conclusion Laparoscopic salpingostomy and laparoscopic salpingectomy are better than laparotomy in the treatment of ectopic pregnancy
文摘Background Recent studies showed that bone marrow-derived mesenchymal stem ceils (BMSCs) had risk of ectopic bone formation. In this study, we aimed to investigate the effect of growth and differentiation factor 6 (GDF-6) on the tenogenic differentiation of BMSCs in vitro, and then combined with small intestine submucous (SIS) to promote tendon regeneration in vivo. Methods The BMSCs were isolated from the green fluorescent protein (GFP) rats, and were characterized by multi-differentiation assays following our previous study protocol. BMSCs cultured with different concentrations of GDF-6, without growth factors served as control. After 2 weeks, mRNA expression and protein expression of tendon specific markers were examined by qRT-PCR and Western blotting to define an optimal concentration of GDF-6. Mann-Whitney U-test was used to compare the difference in relative mRNA expression among all groups; P 〈0.05 was regarded as statistically significant. The GDF-6 treated BMSCs combined with SIS were implanted in nude mice and SD rat acute patellar tendon injury model, the BMSCs combined with SIS served as control. After 12 and 4 weeks in nude mice and tendon injury model, the samples were collected for histology. Results After the BMSCs were treated with different concentration of GDF-6 for 2 weeks, the fold changes of the specific markers (Tenomodulin and Scleraxis) mRNA expression were significantly higher in GDF-6 (20 ng/ml) group (P 〈_0.05), which was also confirmed by Western blotting result. The BMSCs became parallel in orientation after GDF-6 (20 ng/ml) treatment, but the BMSCs in control group were randomly oriented. The GDF-6 (20 ng/ml) treated BMSCs were combined with SIS, and were implanted in nude mice for 12 weeks, the histology showed neo-tendon formation. In the SD rat patellar tendon window injury model, the histology also indicated the GDF-6 (20 ng/ml) treated BMSCs combined with SIS could promote tendon regeneration. Conclusions GDF-6 has tenogenic effect on the tenogenic differentiation of BMSCs, and GDF-6 (20 ng/ml) has better tenogenic effect compared to other concentrations. The GDF-6 (20 ng/ml) treated BMSCs combined with SIS can form neo-tendons and promote tendon regeneration.
基金supported by Youth Innovation Promotion Association CAS(2019031)National Natural Science Foundation of China(51973226,81972081 and 21604093)+3 种基金China Postdoctoral Science Foundation(2020M683733)Military Medical Science and Technology Youth Cultivation Project(20QNPY109)Military Medical Youth Growth Program of PLA General Hospital(QNC19028)Shanghai Changning Committee of Science and Technology of China(CNKW2020Y01).
文摘In the current global crisis of antibiotic resistance,delivery systems are emerging to combat resistant bacteria in a more efficient manner.Despite the significant advances of antibiotic nanocarriers,many challenges like poor biocompatibility,premature drug release,suboptimal targeting to infection sites and short blood circulation time are still challenging.To achieve targeted drug delivery and enhance antibacterial activity,here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin(PEG-Schiff-Van)prodrug and free Van in one drug delivery system.The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition.Notably,on account of the combination of physical encapsulation and chemical conjugation of vancomycin,these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior,which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period.In addition,more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity.Using this strategy,this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites,thereby presenting prominent antibacterial therapy both in vitro and in vivo.This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles,which would be a promising class of antimicrobial materials for potential clinical translation.
基金This study was funded by RemeGen Co.,Ltd.This work was also supported by the National Natural Science Foundation of China(No.91959205)the Ministry of Science and Technology of China(No.2017YFC1308900,No.2018ZX09201-015)Beijing Municipal Health Commission(No.2020-1-1022)。
文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy.
文摘Purpose: To report the practicability and efficacy of autologous iris pigment epithelium (IPE) translocation in exudative age-related macular degeneration (A RMD) over 1 year. Methods: The consecutive interventional case series included 5 6 patients with exudative ARMD. During vitrectomy the submacular neovascular mem brane (CNV) was removed and IPE cells, harvested from a peripheral iridectomy, w ere injected into the submacular space. Included were patients with subfoveal oc cult CNV (11 eyes), classic CNV (10 eyes), mixed CNV (17 eyes), CNV with a pigme nt epithelial detachment (13 eyes) or CNV with a hemorrhage (5 eyes). Outcome me asures were visual acuity, foveal fixation, size of CNV and rate of recurrence b ased on fluorescence angiographic imaging. Results: All patients underwent succe ssful surgical removal of the CNV with consecutive subretinal IPE injection. Vis ual acuity was better than 20/100 in 19 patients preoperatively and in 18 patien ts postoperatively. A visual acuity of 20/100 or less was found in 37 patients p reoperatively and in 38 patients postoperatively. Mean preoperative visual acuit y (1.0±0.3 logMAR units) did not change significantly after 1 year (1.0±0.3 lo gMAR units). Ten eyes (18%) developed a recurrence. Fixation within the surgica lly denuded area could be demonstrated in 25 eyes (45%). Conclusions: Autologou s IPE translocation for ARMD over one year can preserve foveal function on a low level, but cannot improve visual acuity. IPE translocation is technically feasi ble with a low rate of complications. Continued research seems justified to impr ove functional outcome.
文摘Aims: To determine whether central corneal thickness (CCT) is a significant pr edictor of visual field and optic disc progression in open angle glaucoma. Metho ds: Data were obtained from a prospective study of glaucoma patients tested with static automated perimetry and confocal scanning laser tomography every 6 month s. Progression was determined using a trend based approach called evidence of ch ange (EOC) analysis in which sectoral ordinal scores based on the significance o f regression coefficients of visual field pattern deviation and neuroretinal rim area over time are summed. Visual field progression was also determined using t he event based glaucoma change probability (GCP) analysis using both total and p attern deviation. Results: The sample contained 101 eyes of 54 patients (mean (S D) age 56.5 (9.8) years) with a mean follow up of 9.2 (0.7) years and 20.7 (2.3) sets of examinations every 6 months. Lower CCT was associated with worse baseli ne visual fields and lower mean IOP in the follow up. In the longitudinal analys is CCT was not correlated with the EOC scores for visual field or optic disc cha nge. In the GCP analyses, there was a tendency for groups classified as progress ing to have lower CCT compared to nonprogressing groups. In a multivariate analy ses accounting for IOP, the opposite was found, whereby higher CCT was associate d with visual field progression. None of the independent factors were predictive of optic disc progression. Conclusions: In this cohort of patients with establi shed glaucoma, CCT was not a useful index in the risk assessment of visual field and optic disc progression.
文摘Background Reports of applying cervical pedicle screw (CPS) system in the posterior cervical spine surgeries are limited because of its inherent risk of neurovascular injury. The clinical results of cervical spine instability treated with CPS system were retrospectively analyzed, and the clinical efficacy and safety of this management were evaluated. Methods Twenty-five patients with cervical spine instability undergoing posterior C3-C7 single/double door laminoplasty and free-hand CPS fixation as well as graft fusion were investigated; of whom, 3 were due to trauma, and 22 degenerative cervical pathogenesis. One hundred and fifty in total, CPSs were implanted in 5 cervical segments for 1 patient, 4 for 2, 3 for 18, and 2 for 4. Japanese Orthopaedic Association (JOA) score and its improvement rate, neck disability index (NDI), segmental stability, pedicle cortex perforation rate and other complication-associated parameters were assessed. Results The average follow-up was 16.6 (6-30) months. Compared with pre-operative values, JOA score improved by 4.10±0.84 points on average (P 〈0.05) at 6 months post operation, with a mean improvement rate of 61%. While the pre-operative and 6-month post-operative NDI were 32.96_-'_-~.13 and 16.84_+4.40 (P 〈0.05), respectively. At 6-month post-operation and the final follow-up, fused segments were stable. Pedicle cortex perforation rate was 8.0%, with no neurovascular complications observed. Conclusions Anatomizing the pre-operative radiographic data facilitates the precise operative design prior to surgery; and CPS system is capable of offering safe and satisfying outcomes in the management of cervical spine instability.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 81570186) and the Health and Family Planning Commission of Jiangsu Province (No. H201511).
文摘Background: Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes ofrituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated. Methods: A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation. Results: In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number ofrituximab treatment cycles, and OS was only associated with age 〉60 years (P 〈 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively. Conclusions: R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.