[Study on risk prediction model of neck work-related musculoskeletal disorders among automobile manufacturing enterprise workers].

Objective: To explore the risk factors of neck work-related musculoskeletal disorders (WMSDs) among automobile manufacturing enterprise workers, and construct the risk prediction model. Methods: In May 2022, a cluster convenience sampling method was used to selet all front-line workers from an automobile manufacturing factory in Xiangyang City as the research objects. And a questionnaire survey was conducted using the modified Musculoskeletal Disorders Questionnaire to analyze the occurrence and exposure to risk factors of neck WMSDs. Logistic regression was used to analyze the influencing factors of workers' neck WMSDs symptoms, and Nomogram column charts was used to construct the risk prediction model. The accuracy of the model was evaluated by the receiver operating characteristic (ROC) curve, the Bootstrap resampling method was used to verify the model, Hosmer-Lemeshow goodness of fit test was used to evaluate the model, and the Calibration curve was drawn. Results: A total of 1783 workers were surveyed, and the incidence of neck WMSDs symptoms was 24.8% (442/1783). Univariate logistic regression showed that age, female, smoking, working in uncomfortable postures, repetitive head movement, feeling constantly stressed at work, and completing conflicting tasks in work could increase the risk of neck WMSDs symptoms in automobile manufacturing enterprise workers (OR=1.37, 95%CI: 1.16-1.62; OR=2.85, 95%CI: 1.56-5.20; OR=1.50, 95%CI: 1.18-1.91; OR=1.18, 95%CI: 1.02-1.37; OR=1.34, 95%CI: 1.04-1.72; OR=1.62, 95%CI: 1.21-2.17; OR=1.48, 95%CI: 1.13-1.92; P<0.05). While adequate rest time could reduce the risk of neck WMSDs symptoms (OR=0.56, 95%CI: 0.52-0.86, P<0.05). The risk prediction model of neck WMSDs of workers in automobile manutacturing factory had good prediction efficiency, and the area under the ROC curve was 0.72 (95%CI: 0.70-0.75, P<0.001) . Conclusion: The occurrence of neck WMSDs symptoms of workers in automobile manufacturing factory is relatively high. The risk prediction model constructed in this study can play a certain auxiliary role in predicting neck WMSDs symptoms of workers in automobile manufacturing enterprise workers.

A nomogram for predicting low cardiac output syndrome in older patients undergoing acute type A aortic dissection surgery.

OBJECTIVE: Low cardiac output syndrome (LCOS) is a dangerous postoperative complication in patients with acute type A aortic dissection (ATAAD). This study aims to develop and evaluate a nomogram model that can reliably identify risk variables for postoperative LCOS in elderly patients suffering from ATAAD. PATIENTS AND METHODS: In this retrospective study, a total of 310 elderly patients with ATAAD admitted to Fujian Medical University Union Hospital were included and categorized into the LCOS and non-LCOS groups. Stepwise logistic regression was used to analyze independent predictors of LCOS, and a nomogram was constructed. The best clinical decision points were found using decision analysis and a clinical impact curve. RESULTS: Postoperative LCOS occurred in 22 (7.1%) of elderly patients with ATAAD. Independent risk factors for postoperative LCOS were age, smoking history, aortic cross-clamp (ACC), coronary heart disease (CHD), and preoperative shock. The nomogram constructed based on the identified risk factors showed good performance. CONCLUSIONS: Our results suggest that preventive treatment can be administered when needed when the risk of LCOS in older patients with ATAAD after surgery is >60%. This study contributes to developing a methodology that may improve therapeutic decision-making in older patients and provides insights for assessing the risk of LCOS.

[Analysis of symptoms and influencing factors of low back work-related musculoskeletal disorders among workers in a container manufacturing factory].

Objective: To investigate the occurrence of low back work-related musculoskeletal disorders (WMSDs) among workers in a container manufacturing factory, and to explore the influencing factors. Methods: In June 2022, 952 workers from a container factory were selected as the research objects by cluster random sampling. Through questionnaire survey, the incidence of low back WMSDs symptoms among workers in the past one year was collected, and the influencing factors of low back WMSDs were analyzed by logistic regression. Results: The incidence rate of low back WMSDs was 46.7% (445/952). The factors with higher exposure at work were frequent slight bending (77.0%, 733/952), frequent overtime (74.1%, 705/952), and the need to turn around while working (62.3%, 593/952). Multivariate logistic regression analysis showed that age over 40 years old, smoking, drinking, often bending over slightly, sitting for a long time, maintaining a large bending posture for a long time, often working overtime, limited operating space, and there was always a need to complete conflicting things in the container manufacturing factory workers were the risks of increasing the low back WMSDs (OR=1.68, 1.96, 2.47, 1.49, 1.84, 2.11, 1.90, 1.82, 2.00, P<0.05). Standing at work, always friendly colleagues, and always supportive and helpful leaders were protective factors for low back WMSDs (OR=0.60, 0.32, 0.40, P<0.05) . Conclusion: The incidence of low back WMSDs symptoms in container manufacturing workers is high, and work-related factors such as frequent slight bending, long time holding large bending posture and limited operating space are the focus of ergonomic intervention in container manufacturing enterprises.

[Neck musculoskeletal disorders and their influence factors among welders in an automobile factory].

Objective: To explore the prevalence and risk factors of neck musculoskeletal diseases (MSDs) of welders among an automobile factory. Methods: In June 2019, a cluster random sampling method was used to select 677 electric welders from an automobile manufacturing plant in Shiyan City as the survey objects, and a questionnaire survey was conducted using the "Musculoskeletal Disorders Questionnaire" to analyze the prevalence and influencing factors of neck MSDs, and used logistic regression to analyze the relationship between the influencing factors and the prevalence of cervical MSDs. Results: The prevalence rate of MSDs in neck of welders was 54.8% (371/677) . The exposure rate of occupational factors, from high to low, were neckin a bent formord porsure was 71.6% (486/677) , repetitive head movements was 55.1% (373/677) , working in uncomfortable postures was 48.7% (330/677) and neck twisted was 46.8% (317/677) respectively. Sex, age, educational level, length of service, smoking, neck tilt, neck twist, working in uncomfortable posture and head repetitive movements were the risk factors of neck MSDs (P<0.05) . Multiple logistic regression analysis showed that, the main influencing factors of neck MSDs were sex, education level, age, length of service, smoking, neck tilt, working in uncomfortable posture (OR = 2.11, 2.03, 1.83, 1.21, 1.78, 1.90, 1.58, 95%CI: 1.28~3.48、1.47~2.81、1.33~2.52、1.03~1.41、1.22~2.60、1.28~2.83、1.11~2.27, P<0.05) , rest had protective effect on neck MSDs (OR= 0.38, 95%CI: 0.17~0.88, P<0.05) . Conclusion: Welders in automobile factory was highly exposed to occupational risk factors for neck MSDs. Occupational risk factors such as neck in a bent forward posture, working in an uncomfortable posture, prolonged siting, repetitive head movement should be the focus of intervention.

[Investigation on high-frequency hearing loss of noise workers in an automobile factory].

Objective: To investigate the high-frequency hearing loss (HFHL) of workers in an automobile factory and its influencing factors, so as to provide a scientific basis for occupational health management of noise workers. Methods: From March to July 2019, 2647 workers from an automobile factory were selected as the research objects by cluster sampling method. The basic personal information (such as gender, age, education level, height, weight, etc.) , history of ear disease, the history of detonation, history of exposure to ototoxic drugs, history of exposure to occupational noise, etc., were investigated by questionnaire and occupational health examination. Chi-square test was used to compare the detection rates of HFHL in different populations, and multivariate logistic regression model was used to analyze the influencing factors of HFHL. Results: The noise level of 2647 individual workers ranged from 75.0 dB (A) to 92.0 dB (A) , with an average of (84.14±2.47) dB (A) . The detection rate of HFHL was 17.2% (456/2647) . There were significant differences in the the detection rate of HFHL among workers of different gender, age, educational level, working age, noise exposure level, diabetes history, detonation history, smoking and drinking workers (P<0.05) . Multivariate logistic regression analysis showed that male, age ≥30 years old, smoking and noise exposure were risk factors for HFHL (P<0.05) . Conclusion: The detection rate of HFHL in automobile factory workers is high. Gender, age, smoking and noise are the influencing factors of HFHL. It is necessary to strengthen the noise control in the workplace and guide workers to choose healthy lifestyle.

[Prognosis analysis of local recurrence after excision of breast phyllodes tumors].

Objective: To examine treatment outcomes of breast phyllodes tumors and the prognosis factors of local recurrence. Methods: This retrospective cohort study included 276 patients who underwent surgical resection at Breast Center, Peking University People's Hospital from January 2011 to December 2019. Tumor subtype and histopathological features were determined from pathology reports, and the deadline of follow-up was September 30th, 2020. All 276 patients underwent open surgery, including 17 patients of mastectomy, and 259 patients of lumpectomy. The enrolled patients were all female, with age of (41.5±11.3) years (rang: 11 to 76 years), and tumor diameter of 35(28) mm (M(QR)). The Kaplan-Meier method and Log-rank test were used for survival analysis. The multivariate analysis was implemented using the Cox proportional hazard model. Results: According the pathologic test, there were 191 patients of benign phyllodes tumor, 67 patients of borderline tumor and 18 patients of malignant tumor. There were 249 patients with a follow-up of more than 6 months, and 14.1% (35/249) had local recurrence. The time-to-recurrence was (28.6±22.2) months (range: 2 to 96 months), (29.1±18.1) months (range: 2 to 80 months), (32.1±30.1) months (range: 5 to 96 months) and (12.0±6.9) months (range: 8 to 20 months) for benign, borderline and malignant phyllodes tumors. Tumor diameter (≥100 mm vs.<50 mm, HR=3.968, 95%CI: 1.550 to 10.158, P=0.004) and malignant heterologous element (yes vs. no, HR=26.933, 95%CI: 3.105 to 233.600, P=0.003) were prognosis factors of local recurrence. One death from malignant phyllodes occurred after distant metastasis. The 3-year disease-free survival rates of benign, borderline and malignant phyllodes tumor were 88.2%, 81.7% and 81.4% (P=0.300). Conclusion: Phyllodes tumors have a considerable local recurrence rate, which may be associated with tumor diameter and malignant heterologous element.

[Epidemiological analysis and screening mode of breast cancer screening in Fujian province from 2015 to 2018].

Objective: To analyze the screening results of breast cancer in rural women in Fujian Province from 2015 to 2018, and to explore the screening mode of breast cancer. Methods: Breast cancer screening was provided for 35-64 years old rural women in Fujian province. Color Doppler ultrasound was used as the primary screening method. Suspected patients were referred to mammography. Color Doppler ultrasound and breast X -ray 4-5 grade were diagnosed by pathology. Results: The incidence of breast cancer from 2015 to 2018 was 56.96/10 million, 94.41/10 million, 71.61/10 million, and 73.05/10 million, respectively. And the peak age of breast cancer was (46-55) years. From 2015 to 2018, the proportion of cancer in situ showed an overall upward trend. The sensitivity of color Doppler ultrasound was 79.06%, and the sensitivity of mammography for those diagnosed abnormally by ultrasound was 91.88%. Conclusion: Breast cancer screening for women of the right age is an important measure to raise the rate of early diagnosis and early treatment and reduce the mortality of breast cancer. Screening mode based on breast ultrasound is the most suitable technology. We need to further expand the coverage of screening, improve the screening system and process, and ensure the health of women.

Curcumin exerts protective effect on PC12 cells against lidocaine-induced cytotoxicity by suppressing the formation of NLRP3 inflammasome.

OBJECTIVE: To explore the protective effect of curcumin on lidocaine-insulted PC12 cells. MATERIALS AND METHODS: We first treated PC12 cells with different doses of lidocaine, and then treated the cells with curcumin or Nod-like receptor pyrin domain3 (NLRP3) inhibitor (MCC950). Subsequently, the cell viability, apoptosis, reactive oxygen species (ROS) production and NLRP3 inflammasome were detected by cell counting kit-8 (CCK8), Annexin V/PI staining, FCM and Western blot analysis, respectively, and the level of IL-1ß in PC12 cells was determined by an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Lidocaine inhibited the viability of PC12 cells, and it induced cell apoptosis, promoted ROS release and activated NLRP3 inflammasome in PC12 cells, but its effects were reversed by the treatment of curcumin. Moreover, NLRP3 over-expression also induced cytotoxicity in PC12 cells, which was also rescued by the treatment of curcumin. CONCLUSIONS: Our study indicates that curcumin exerts protective effect against lidocaine-induced cytotoxicity on PC12 cells by suppressing the activity of NLRP3 inflammasome, which provides new ideas on screening natural product for neurological damage therapy.

[Computer Aided Diagnosis system of breast ultrasound based on support vector machine: a clinical analysis].

Objective: To investigate the value of based on support vector machine (SVM) breast ultrasonography technology of Computer-Assisted diagnosis (CAD) for differential diagnosis of benign and malignant breast masses. Methods: Total of 143 patients who had 151 breast masses were collected in Fujian Maternity and Children Health Hospital or The Fist Affiliated Hospital of Fujian Medical University from June 2014 to December 2015. Based on pathological results as the gold standard, the diagnostic efficiency of CAD and ultrasonography were compared. Results: The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of ultrasonography were 80.1%, 71.0%, 76.8%, 80.0% and 72.1%, respectively. And the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of CAD were 96.6%, 90.3%, 94.0%, 93.5% and 94.9%, respectively. The specificity, accuracy, positive predictive value and negative predictive of CAD technology were significantly higher than those of ultrasonography (P<0.05). The area under the receiver operator characteristic curve of ultrasonography and CAD were 0.759 and 0.935 respectively, with significant difference (P<0.05). Conclusions: CAD has a higher specificity and accuracy rate than ultrasonography in the diagnosis of breast masses. It could help to differentiate benign from malignant breast masses.

Ultralow-frequency Raman system down to 10 cm(-1) with longpass edge filters and its application to the interface coupling in t(2+2)LGs.

Ultralow-frequency (ULF) Raman spectroscopy becomes increasingly important in the area of two-dimensional (2D) layered materials; however, such measurement usually requires expensive and nonstandard equipment. Here, the measurement of ULF Raman signal down to 10 cm(-1) has been realized with high throughput by combining a kind of longpass edge filters with a single monochromator, which are verified by the Raman spectrum of L-cystine using three laser excitations. Fine adjustment of the angle of incident laser beam from normal of the longpass edge filters and selection of polarization geometry are demonstrated how to probe ULF Raman signal with high signal-to-noise. Davydov splitting of the shear mode in twisted (2+2) layer graphenes (t(2+2)LG) has been observed by such system in both exfoliated and transferred samples. We provide a direct evidence of twist-angle dependent softening of the shear coupling in t(2+2)LG, while the layer-breathing coupling at twisted interfaces is found to be almost identical to that in bulk graphite. This suggests that the exfoliation and transferring techniques are enough good to make a good 2D heterostructures to demonstrate potential device application. This Raman system will be potentially applied to the research field of ULF Raman spectroscopy.

In vitro and in vivo studies on the inhibitory effects of myocardial cell culture medium on growth of a human lung adenocarcinoma cell line, A549.

BACKGROUND: Although the heart is one of the body's vital organs, with an abundant blood supply, metastasis to the heart is considered rare. In a previous study, we found that the myocardial microenvironment might contain a low molecular weight natural tumour suppressor. The present study was designed to investigate the inhibitory effect of cardiac myocyte-conditioned medium (cmcm) on the growth of A549 human lung adenocarcinoma cells in vitro and in vivo. METHODS: An mtt assay was used to detect the inhibition ratio with respect to A549 proliferation. Human lung adenocarcinoma cells (A549 cell strain) were transplanted subcutaneously into nude mice to produce tumours. The xenograft tumour growth in mice was observed after selected drug administration. RESULTS: After treatment with cmcm and cisplatin (Cis), A549 cell viability significantly declined (p < 0.001). The cell viability in the cmcm and Cis groups were 53.42% ± 3.45% and 58.45% ± 6.39% respectively. Growth of implanted tumour cells in vivo was significantly inhibited in the cmcm group, the group treated with recombinant human adenovirus-p53, and the Cis-treated group compared with a control group. The inhibition rates were 41.44% in the cmcm group, 41.34% in the p53 group, and 64.50% in the Cis group. Lung metastasis capacity was significantly reduced in the presence of cmcm (p < 0.05). Lung metastasis inhibition rates in mice were 56.52% in the cmcm group, 47.83% in the p53 group, and 82.61% in the Cis group. With cmcm, the lives of A549-tumour-bearing mice could be significantly prolonged without any effect on weight loss. CONCLUSIONS: Use of cmcm has the effect of reducing A549 cell viability, tumour volume, and lung metastasis rate, while prolonging survival duration without severe toxicity.

Role of methylenetetrahydrofolate reductase C677T and A1298C polymorphisms in polycystic ovary syndrome risk.

Polycystic ovary syndrome is one of the most frequently encountered endocrine malfunctions. Methylenetetrahydrofolate reductase (MTHFR) plays a vital role in folate metabolism, DNA methylation, and RNA synthesis. We carried out a study to investigate the association between MTHFR C677T and A1298C genetic variations and the risk of polycystic ovary syndrome in a Chinese population. We recruited 244 patients and 257 control subjects from an Inner Mongolian Medical University to this hospital-based, case-control study. The genotyping of the MTHFR C677T and A1298C polymorphisms was carried out using polymerase chain reaction coupled with restriction fragment length polymorphism. Using multiple logistic regression analysis, we found that the TT genotype and the T allele of MTHFR C677T carriers showed increased risk of polycystic ovary syndrome compared with the wild-type genotype or allele carriers. The adjusted ORs for the TT genotype and the T allele of MTHFR C677T were 1.84 (1.05-3.26) and 1.38 (1.06-1.81), respectively. Subjects carrying the CC genotype (OR = 3.98, 95%CI = 1.60-11.23) and the C allele (OR = 1.46, 95%CI = 1.07-2.00) of MTHFR A1298C had an elevated risk of polycystic ovary syndrome compared with the AA genotype and A allele carriers. In conclusion, our study suggests that the MTHFR C677T and A1298C polymorphisms may have contributed to the risk of polycystic ovary syndrome in the Chinese women investigated. Further research involving a greater number of individuals is warranted to confirm our results.

Invasive ductal breast cancer with extensive subcutaneous metastases in trunk: a case report.

The metastases sites of advanced breast cancer contain vast majority of tissues and organs, which most common are bones, lungs, liver, brain and distant lymph nodes. We report a woman with unusual extensive subcutaneous metastases of breast cancer in her abdomen, back and back of the neck. The patient was diagnosed with invasive ductal breast cancer and had been treated 4 months earlier with modified radical mastectomy and three cycles of chemotherapy. Later she presented painless multiple small tubercules on the abdomen wall, back and back of the neck. She sought treatment in our department to perform a 18FDG PET-CT scan, confirming the multiple subcutaneous tubercules. Histopathological studies supported that the tubercules were rare subcutaneous metastatic of breast origin. The patient underwent another two cycles of chemotherapy and evaluation of curative effect was stability.

Sorafenib combined with transarterial chemoembolization for the treatment of advanced hepatocellular carcinoma: a large-scale multicenter study of 222 patients.

BACKGROUND: Data on the efficacy and safety of sorafenib in combination with transarterial chemoembolization (TACE) in patients with advanced hepatocellular carcinoma (HCC) are lacking. PATIENTS AND METHODS: In this multicenter retrospective study, 222 consecutive HCC patients receiving combination therapy were enrolled between June 2008 and July 2011. RESULTS: Chronic hepatitis B was the predominant cause of HCC (86%). Eighty percent patients were at Barcelona Clinic Liver Cancer (BCLC) stage C, and 86% patients were in Child-Pugh (CP) A class. The overall median survival was 12 months (95% CI 10.1-13.9). The overall incidence of adverse events (AEs) was 87%. In 177 BCLC-C patients, performance status, the number of HCC nodules, Child-Pugh score and macrovascular invasion were significantly associated with overall survival (OS) and were included in the final risk scores (R), where R = 5 × (vascular invasion: 0 if no, 1 yes) + 6 × (CP: 0 if A, 1 if B) + 7 × (no. of lesions: 0 if 1-2, 1 ≥3) + 8 × ( Eastern Cooperative Oncology Group, ECOG: 0 if 0, 1 ≥1). CONCLUSIONS: Sorafenib in combination with TACE should be considered a safe and effective therapy for advanced HCC. Further validation of the new subgroup of BCLC-C stage is warranted in an independent patient cohort.

Kinsenoside prevents ovariectomy-induced bone loss and suppresses osteoclastogenesis by regulating classical NF-κB pathways.

UNLABELLED: Kinsenoside is able to improve bone turnover rate in ovariectomized (OVX) mice. In vitro analysis shows that kinsenoside antagonizes osteoclast development and bone resorption. INTRODUCTION: Kinsenoside, the main active compound of the traditional Taiwanese herb Anoectochilus formosanus, has an antiinflammatory effect. This study investigates whether kinsenoside inhibits osteoporosis and osteoclastogenesis. METHODS: OVX mice were used to examine the antiosteoporotic activity of kinsenoside. The trabecular bone microarchitecture was assessed by microcomputed tomography. In vitro experiments were performed to determine the mechanisms of the antiosteoporotic effects of kinsenoside. RESULTS: Microcomputed tomography scanning showed that kinsenoside suppresses bone loss in OVX mice. Kinsenoside decreases plasma CTx concentration. Reverse transcription polymerase chain reaction (RT-PCR) analysis also showed that kinsenoside reduces the femoral mRNA expression of tartrate-resistant acid phosphatase (TRAP) and matrix metalloproteinase-9 (MMP-9). Kinsenoside inhibits osteoclast formation in bone marrow cells (BMs) and RAW 264.7 cells. Western blot was used to analyze osteoclast-associated signaling pathways in RAW 264.7 cells. Results show that kinsenoside does not inhibit IKK phosphorylation but suppresses the phosphorylation of IκBα and p65. Kinsenoside significantly inhibits the RANKL induction of IKK activity. Kinsenoside inhibits the RANKL-triggered nuclear translocations of NF-κB and nuclear factor of activated T cells c1 (NFATc1). RT-PCR was used to analyze osteoclast precursor fusion and resorption-associated gene expression in BMs. Kinsenoside inhibits the expression of cathepsin K (CAK), dendritic cell-specific transmembrane protein, MMP-9, and TRAP. CONCLUSIONS: Kinsenoside inhibits osteoclastogenesis from macrophages by attenuating RANKL-induced NF-κB and NFATc1 activities, which in turn, prevents bone loss from OVX mice.

Effects of siRNA-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism.

To observe the effects of small interfering RNA (siRNA)-targeting bone morphogenetic protein (BMP)-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells and its mechanism. Three siRNAs-targeting BMP-2 gene were synthesized. There were six groups including group I (non-transfected cells), group II (only liposome-transfected cells), group III (non-specific siRNA-transfected cells) and groups IV-VI (siRNA-A, siRNA-B and siRNA-C-targeting BMP-2 transfected cells, respectively). SMMC7721 cells were instantaneously transfected using lipofectamine method. The levels of mRNA and protein of BMP-2 in cells were determined with reverse transcription-PCR and western blotting. The abilities of migration and invasion of transfected cells were assessed using scratch test and in vitro invasion assay, respectively. The protein levels of p-ERK, p-JNK and p-p38 and the protein levels of MMP-2 and MMP-9 were evaluated with western blot 48 h after siRNA-B-targeting BMP-2 was transfected into liver cancer SMMC7721 cells. Expression of mRNA and protein of BMP-2 in groups IV-VI were significantly inhibited, especially in group V. Cell scratch width was significantly greater in group V than in group I and III (P<0.01). In vitro invasion assay suggested that the number of invasion of cells was significantly lower in group V than in group I and III (P<0.05). Western blot indicated that the level of p-ERK was significantly decreased (P<0.05), the levels of p-JHK and p-p38 were not significantly changed and the levels of MMP-2 and MMP-9 were significantly downregulated (P<0.05). siRNA-targeting BMP-2 can markedly inhibited the expression of BMP-2 in liver cancer SMMC7721 cells, and decrease the abilities of migration and invasion of liver cancer cells, especially siRNA-B. The inhibitory effects of siRNA-B-targeting BMP-2 on the abilities of migration and invasion of human liver cancer SMMC7721 cells may be caused by the downregulation of MMP-2 and MMP-9 through MAPK/ERK pathway, whereas is not related to MAPK/JNK and MAPK/p38 pathway.

Mutations in the ATP2C1 gene in Chinese patients with Hailey-Hailey disease.

Hailey-Hailey disease (HHD; MIM 16960) is a rare autosomal dominant hereditary disorder characterized by recurrent eruption of vesicles and bullae, predominantly involving the body folds. It is caused by heterozygous mutations in the ATP2C1 gene, encoding the human secretory pathway Ca2+/Mn2+-ATPase protein 1 (hSPCA1). When we studied Chinese patients with HHD, we found two different heterozygous mutations, Q506X and G353V, the former previously reported in a Hungarian patient, and the latter being a novel mutation. In a 38-year-old patient from a four-generation pedigree with a 3-year history of severe recurrent blisters, we identified a C-->T transition at nucleotide 1696, c(1696C-->T), in exon 17 of ATP2C1, resulting in a nonsenes mutation, Gln506X, which resulted in a premature termination codon. In the second patient, who represented a occurrence of sporadic Hailey-Hailey disease, a G-->T transversion of nucleotide, c(G1238T), in exon 13 of ATP2C1 was detected, which resulted in a Gly353-->Val amino acid substitution (G353V). Our molecular findings further demonstrate that the mutational events in the human ATP2C1 gene encoding the hSPCA1 pump play an important role in the pathogenesis of HHD.

[Preparation and biological activities of monoclonal antibody-streptonigrin immunoconjugates].

The clinic use of streptonigrin (114B), a highly active antitumor antibiotic, is limited by its detrimental effects on normal tissues. In an attempt to improve its specificity streptonigrin was conjugated to anti-human hepatoma monoclonal antibody 3A5 by four different chemical linkage methods. The first method was via water-soluble carbodiimide (EDCI) to create conjugates (1); in the second, an active ester of streptonigrin was applied as a reactive intermediate (2); and in the other two, spacers were put to use for coupling streptonigrin to McAb 3A5-Dextran T-40 (3) or McAb 3A5-bovin serum albumin (BSA) (4). The conjugates showed biological activities and UV spectral characteristics of streptonigrin and 3A5. As determined by clonogenic assay with human hepatoma BEL-7402 cells for 1 hour exposure, the IC50 for conjugate (2), conjugate (3) and streptonigrin were 0.355 ng/ml, 1.23 ng/ml and 22.4 ng/ml, respectively. The potency of conjugates (2) and (3) were 63-fold and 18-fold stronger than that of free streptonigrin. Clonogenic assay with KB cells which weakly react with 3A5 by Elisa showed that the potency of conjugate (2) and (3) were 11-fold and 13-fold weaker than free streptonigrin, respectively. The results suggest that the conjugates of McAb 3A5 and streptonigrin show specific cytotoxicity to target liver cancer cails. The linkage groups of streptonigrin were also discussed.

Free transfer of the second toe combined with dorsalis pedis flap using microvascular technique for reconstruction of the thumb and other fingers.

The blood supply to the dorsum of the feet was studied in 100 cadaver feet specimens. The understanding of anatomical variation of branches of dorsalis pedis artery and its venous system are important in determining the success of the operation for free toe or dorsalis pedis flap transplantation. Three groups of fine branches of arterial system supplying the skin on the dorsum of the feet are classified; the central, the intermediate and the marginal groups. The central group is the dorminant blood supply to the dorsalis pedis skin flap. The first dorsal metatarsal artery which is a main branch of the dorsalis pedis artery remains to be dominant feeding artery to the second toe. From these cadaver specimens, three types of distribution are formulated, but with different percentages of distribution as compared with that of Gilbert's data. Seven consecutive cases of the second toe combined with dorsalis pedis flap transfer using microvascular technique for the reconstruction of thumb and other fingers are reported. The operation is designed to meet the demand of one stage reconstruction of the missing thumb or other fingers which are associated with surrounding soft tissue defects. Preparatory soft tissue repair by skin flap or tube flap is thus obviated.