The role of HPV11 E7 in modulating STING-dependent interferon ß response in recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare benign tumor caused mainly by the infection of the respiratory tract epithelial cells by the human papillomavirus (HPV) type 6/11. However, the specific mechanisms underlying the inhibition of the host's innate immune response by HPV remain unclear. For this purpose, we employed single-cell RNA sequencing to analyze the states of various immune cells in RRP samples post-HPV infection and utilized a cellular model of HPV infection to elucidate the mechanisms by which HPV evades the innate immune system in RRP. The results revealed distinct immune cell heterogeneity in RRP and demonstrated that HPV11 E7 can inhibit the phosphorylation of the stimulator of interferon genes protein, thereby circumventing the body's antiviral response. In vitro co-culture experiments demonstrated that stimulation of macrophages to produce interferon-beta induced the death of HPV-infected epithelial cells, also reducing HPV viral levels. In summary, our study preliminarily identifies the potential mechanisms by which HPV evades the host's antiviral immune response, as well as the latent antiviral functions exhibited by activated macrophages. This research serves as an initial exploration of antiviral immune evasion in RRP, laying a solid foundation for investigating immunotherapeutic approaches for the disease.IMPORTANCESurgical tumor reduction is the most common treatment for recurrent respiratory papillomatosis (RRP). One of the characteristics of RRP is its persistent recurrence, and multiple surgeries are usually required to control the symptoms. Recently, some adjuvant therapies have shown effectiveness, but none of them can completely clear human papillomavirus (HPV) infection, and thus, a localized antiviral immune response is significant for disease control; after all, HPV infection is limited to the epithelium. Inhibition of interferon-beta (IFN-ß) secretion by HPV11 E7 viral proteins in epithelial cells by affecting stimulator of interferon genes phosphorylation may account for the persistence of low-risk HPV replication in the RRP. Moreover, suppression of the IFN-I pathway in RRP cell types might provide clues regarding the hyporeactive function of local immune cells. However, activation of macrophage groups to produce IFN-ß can still destroy HPV-infected cells.

Effectiveness of surgery combined with photodynamic therapy for recurrent respiratory papillomatosis.

OBJECTIVE: This study aims to analyze the safety and effectiveness of a new model of surgery combined with Photodynamic therapy for treating Recurrent Respiratory Papillomatosis (RRP). METHODS: Review the case data of patients with RRP who opted for comprehensive surgery combined with Photodynamic therapy at the Nanjing BenQ Medical Center, from January 2021 to May 2023. The efficacy of this program was evaluated by comparing the annual number of surgeries and Derkay scores before and after the surgery. RESULTS: A total of 23 RRP patients were included in the study. After treatment, the recurrence rate was 65.2 % (15/23), with an average recurrence time of 94.3 ± 50.8 days. The average Derkay score at the time of recurrence was significantly lower than the average pre-treatment Derkay score (P < 0.001). The average annual recurrence rate before treatment was 2.2 ± 1.3, compared to 1.5 ± 1.5 after treatment, with no significant difference (P = 0.16). However, subgroup analysis revealed a significant decrease in the annual recurrence rate of adult-onset RRP after treatment (P = 0.01). The most common adverse reaction was mild pharyngeal pain (11/23). There were 3 cases of new-onset vocal cord adhesions. No patients experienced serious respiratory-related adverse reactions, anesthesia-related adverse reactions, or systemic phototoxic reactions. CONCLUSION: In conclusion, this study indicates that surgery combined with Photodynamic therapy (PDT) might be a safe and effective option for treating RRP, especially in patients with Adult-Onset Recurrent Respiratory Papillomatosis (AORRP).

Recurrence and malignant transformation of laryngeal leukoplakia treated with CO2 laser: A systematic review and meta-analysis.

BACKGROUND: Laryngeal leukoplakia (LL) is a white lesion with high potential of recurrence and malignant transformation. Currently, CO2 laser has become the primary surgical treatment for LL, and the recurrence and malignant transformation rates after treatment vary widely. OBJECTIVE: We performed a systematic review and meta-analysis dedicated to evaluating the rates of recurrence and malignant transformation of LL lesions treated with CO2 laser and exploring relevant risk factors for recurrence or malignant transformation. METHODS: Literature searches were conducted on ProQuest, PubMed, Web of Science, Ovid Medline, Embase, and Cochrane databases. Some articles identified through hand searching were included. RESULTS: A total of 14 articles and 1462 patients were included in this review. Pooled results showed that the overall recurrence rate was 15%, and the malignant transformation rate was 3%. Subgroup analysis showed that the dysplasia grade was not a significant risk factor for the recurrence and malignant transformation of LL (P > .05). CONCLUSIONS: The results of this systematic review and meta-analysis suggest that the CO2 laser is a safe and effective surgical instrument for the excision of LL, which yields low rates of recurrence and malignant transformation. The risk factors relevant to recurrence or malignant transformation remain unclear and require further investigation.

USP33 promotes nonalcoholic fatty acid disease-associated fibrosis in gerbils via the c-myc signaling.

Nonalcoholic fatty acid disease (NAFLD) is a common complication of obesity associated with liver fibrosis. The underlying molecular mechanisms involved in the progression from normal to fibrosis remain unclear. Liver tissues from the liver fibrosis model identified the USP33 gene as a key gene in NAFLD-associated fibrosis. USP33 knockdown inhibited hepatic stellate cell activation and glycolysis in gerbils with NAFLD-associated fibrosis. Conversely, overexpression of USP33 caused a contrast function on hepatic stellate cell activation and glycolysis activation, which was inhibited by c-Myc inhibitor 10058-F4. The copy number of short-chain fatty acids-producing bacterium Alistipes sp. AL-1, Mucispirillum schaedleri, Helicobacter hepaticus in the feces, and the total bile acid level in serum were higher in gerbils with NAFLD-associated fibrosis. Bile acid promoted USP33 expression and inhibiting its receptor reversed hepatic stellate cell activation in gerbils with NAFLD-associated fibrosis. These results suggest that the expression of USP33, an important deubiquitinating enzyme, is increased in NAFLD fibrosis. These data also point to hepatic stellate cells as a key cell type that may respond to liver fibrosis via USP33-induced cell activation and glycolysis.

RUNX1 promotes MAPK signaling to increase tumor progression and metastasis via OPN in head and neck cancer.

Tumor progression and metastasis are still major burdens for head and neck squamous cell carcinoma (HNSCC). Runt-related transcription factor 1 (RUNX1) is involved in aggressive phenotypes in several cancers, while the molecular role of RUNX1 underlying cancer progression and metastasis of HNSCC remains largely unknown. In our study, RUNX1 expression was increased with disease progression in patients with HNSCC. The silencing of RUNX1 significantly decelerated the malignant progression of HNSCC cells, reduced osteopontin (OPN) expression in vitro and weakened the tumorigenicity of HNSCC cells in vivo. Moreover, we demonstrated that RUNX1 activated the mitogen-activated protein kinase signaling by directly binding to the promoter of OPN in tumor progression and metastasis of HNSCC. Our results may provide new insight into the mechanisms underlying the role of RUNX1 in tumor progression and metastasis and reveal the potential therapeutic target in HNSCC.

Combined application of multiple autosomal and Y-chromosomal STR loci in solving a homicide case in 2009.

In 2009, a violent murder occurred. Two victims, a 47-year-old mother and her 21-year-old daughter, were murdered at home. After importing the 20 autosomal STR loci and 27 Y-STR loci into a database, no hit had been found. In 2019, a person with a prior criminal record was matched in the national forensic Y-STR database. When increasing the number of detected Y-STR loci to 60, all loci of the bloodstain donor at the crime and the suspect were still found to be identical. With the combined calculation of multiple autosomal STR and kinship index, we were able to identify the perpetrator as a previously unknown illegitimate child of a large family and solved the case.

[Effect of Mobile Health for Standardized Management on Women with Gestational Diabetes Mellitus].

Objective To explore the performance of mobile health platform for standardized management of pregnant women with gestational diabetes mellitus(GDM). Methods A randomized controlled trial was conducted,in which 295 women with GDM were randomized into two groups(traditional management group and mobile health management group)by a computer-generated sequence.The traditional management group accepted standardized GDM management,and the mobile health management group was supplemented by mobile health management based on the standardized management.The glycemic control rate and the incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit were compared between the two groups. Results The glycemic control rate in mobile health management group was significantly higher than that in the traditional management group [(67.22±22.76)% vs.(60.69±21.28)%,P=0.004].The incidences of low birth weight,macrosomia,preterm birth,premature rupture of membranes,postpartum hemorrhage after cesarean section,neonatal asphyxia,malformation,and admission to the neonatal intensive care unit demonstrated no significant differences between groups(all P > 0.05). Conclusions Mobile health applied in standardized management is conducive to the glycemic control of GDM women,whereas it does not significantly improve the pregnancy outcomes.Due to the short time of intervention,the effects of mobile health on pregnancy outcomes need further study.

Upregulation of secreted phosphoprotein 1 affects malignant progression, prognosis, and resistance to cetuximab via the KRAS/MEK pathway in head and neck cancer.

Acquired resistance is a barrier to cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Secreted phosphoprotein 1 (SPP1) is involved in various biological processes, including immune responses, cancer progression, and prognosis in many cancers, while little is known in HNSCC. Bioinformatics methods were used to identify candidate genes and further in vivo and in vitro experiments were performed to examine and validate the function of SPP1. We found that SPP1 was upregulated and has been found to have an oncogenic role in HNSCC. We further confirmed that overexpression of SPP1 affected proliferation, migration, invasion, and survival, and inhibited apoptosis, whereas silencing of SPP1 yielded opposite results to those of SPP1 overexpression. In addition, activation of the KRAS/MEK pathway contributed to the SPP1-induced malignant progression of HNSCC and resistance to cetuximab. Furthermore, SPP1 knockdown or an MEK inhibitor overcame this cetuximab-resistance pattern. Taken together, our findings for the first time identify the role of SPP1 in tumor promotion, prognostic prediction, and potential therapeutic targeting, as well as resistance to cetuximab in HNSCC.

High Hexavalent Chromium Concentration in Groundwater from a Deep Aquifer in the Baiyangdian Basin of the North China Plain.

Hexavalent chromium (Cr(VI)) is known to occur naturally in shallow oxic groundwater, typically from aquifers associated with mafic and ultramafic formations, but information on the occurrence of Cr(VI) in deep groundwater from large sedimentary basins is limited. This study shows that groundwater from the Baiyangdian Lake Basin (BYB), home to the future second capital city of China, had high Cr concentration (>10 µg/L, up to 86 µg/L) in the deep aquifer (>150 m), while shallow groundwater had lower Cr concentration (<10 µg/L). Chromium occurred predominantly as Cr(VI) (>95%). Shallow groundwater was characterized by higher Mn and Fe concentrations relative to deep groundwater, likely indicating more reducing conditions. Sequential extraction experiments from aquifer sediments suggest that Cr(VI) may derive from silicate weathering and that Mn oxides in the aquifer play a major role in the formation of Cr(VI) in groundwater. Inverse correlations between Mn and Cr(VI) suggest that reductive dissolution of Mn oxides constrains Cr(VI) mobilization in the shallow groundwater, while oxic-suboxic conditions in the deep aquifer limit Mn solubility, which enhances oxidation of Cr(III) to Cr(VI) and promotes desorption of Cr(VI) under alkaline conditions. This study demonstrates the potential geogenic occurrence of high Cr(VI) concentration in deep groundwater from a nonmafic, large sedimentary basin containing Mn oxides in the aquifer sediments.

A cross-sectional study of the relationships between different components of sarcopenia and brachial ankle pulse wave velocity in community-dwelling elderly.

BACKGROUND: Previous studies have just found skeletal muscle mass decline is associated with arterial stiffness, but it is unclear whether muscle strength and physical performance as important compositions of sarcopenia are associated with arterial stiffness. The aim of this study was to investigate the relationship between sarcopenia, the components of sarcopenia and arterial stiffness among elderly in the community. METHODS: This study enrolled 450 elderly people who received general medical examinations in Tianjin First Center Hospital. Each of the subjects was greater than 65 years old, including 266 male and 184 female subjects. Based on the diagnostic criteria for sarcopenia in older people developed by the Asian Working Group for Sarcopenia (AWGS), 89 subjects were separated into the sarcopenia group. The living habits, disease status, general status and laboratory examinations of all subjects were collected. The body composition (including appendicular skeletal muscle mass and visceral fat area (VFA) of each participant) was measured by bioimpedance analysis. HS, usual gait speed (GS), and brachial ankle pulse wave velocity (baPWV) were measured. RESULTS: Sarcopenia subjects had higher baPWV, nutrition risk and lower appendicular skeletal muscle index (ASMI), Handgrip strength (HS), GS, body mass index (BMI), triacylglycerol (TG), serum albumin (ALB) and creatinine (Cr) than did non-sarcopenia subjects; Sarcopenia subjects also had higher visceral fat area (VFA) than did non-sarcopenia subjects (p < 0.05). ASMI and HS were negatively associated with baPWV (t = - 5.807, p = 0.000 and t = - 3.085, p = 0.002), but the relationship between baPWV and GS was not statistically significant (t = - 0.862, p = 0.389) by multivariable linear regression. After adjusting for confounders, a multivariate logistic regression analysis revealed that sarcopenia was related with age, BMI, sports and baPWV in community dwelling elderly. CONCLUSIONS: ASMI and HS were negatively associated with baPWV in community dwelling elderly in China; and baPWV was a risk factor of sarcopenia.

Selenite removal and reduction by growing Aspergillus sp. J2.

In this study, the removal and reduction of selenite [Se(IV)] by growing Aspergillus sp. J2 were investigated. The lag phase, growth rate and biomass of J2 was not significantly influenced by the presence of 100 mg/L Se(IV). A rapid Se(IV) removal process took place from the 3rd to the 4th day during the growth of J2. Scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy and X-ray diffraction analyses showed that the Se(IV) did not cause any visible effects on cell morphology and the reduced amorphous elemental selenium [Se(0)] nanoparticles were mainly on the surface of the mycelial cell walls. The macromolecules containing amine groups also interact with Se(IV) and could play an important role in Se(IV) removal by J2.

Study on relationship between elderly sarcopenia and inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10.

BACKGROUND AND OBJECTIVES: The pathophysiological mechanism of sarcopenia in the elderly has not yet been fully understood. Here, we aim to explore the relationship between sarcopenia and the inflammatory cytokine interleukin-6 (IL-6), and the anti-inflammatory cytokine interleukin-10 (IL-10) in an elderly population. METHODS: Our study comprised 118 males and 46 females aged between 61 and 90 who had received a general medical examination in Tianjin First Central Hospital. Subjects were divided into a sarcopenia group and a non-sarcopenia group, defined according to the criteria of the Asian Working Group for Sarcopenia (AWGS). We compared body composition, handgrip strength (HS), gait speed (GS), biochemical indexes, levels of IL-6 and IL-10, living habits, and disease status between these groups. RESULTS: Non-sarcopenia subjects undertook more regular physical exercise than sarcopenia patients. Sarcopenia subjects had higher nutrition risk but lower body mass index (BMI), serum albumin (ALB), triglyceride (TG), and creatinine (Cr) levels compared to non-sarcopenia subjects. Sarcopenia subjects were older and had higher visceral fat tissue (VFA) than non-sarcopenia subjects (P < 0.05), along with higher IL-6 and IL-10 levels. Furthermore, IL-6/IL-10 ratios were higher in subjects with sarcopenia (P < 0.05). Age, BMI, levels of physical activity, nutritional risk, VFA, IL-6, IL-10, IL-6/IL-10 ratio were independently associated with the presence of sarcopenia in univariate regression analyses. Following adjustment for confounding factors, the presence of sarcopenia was positively correlated with IL-6, IL-10, IL-6/IL-10 ratio and inversely correlated with BMI. Age is associated with increased presence of sarcopenia. CONCLUSIONS: The levels of inflammation cytokine IL-6, anti-inflammatory IL-10 and IL-6/IL-10 ratio were increased in elderly sarcopenia subjects. Sarcopenia was associated with increased levels of inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10, and IL-6/IL-10 ratios.

Click chemistry functionalization improving the wideband optical-limiting performance of fullerene derivatives.

A novel kind of monodonor-bisacceptor (D-A-A) C60 charge-transfer complex was synthesized by the high-yielding [2+2] click chemistry reaction and the Prato reaction. Both electrochemical and UV-vis spectra studies were carried out and they proved that the side groups of the fullerene derivatives played an important role in the energy gaps, and also affected the third-order non-linear optical response. The experimental investigation on the third-order non-linear optical phenomena of the fullerene derivatives was measured using the Z-scan technique at different wavelengths (532 nm and 1064 nm). All the compounds exhibited very special non-linear optical properties when pumped by 21 ps pulses at 532 nm which suggested that there were two different types of reversible photo-isomerization. The optical-limiting performance has also been studied which proved indirectly the mechanism models of the reversible photo-isomerization.

[Laparoscopic high uterosacral ligament suspension combined with cervical amputation in treatment of women severe uterine prolapsed at child-bearing period].

OBJECTIVE: To evaluate clinical and sexual outcomes in women with severe uterine prolapsed at child-bearing period undergoing laparoscopic high uterosacral ligament suspension combined with cervical amputation. METHODS: From November 2007 to March 2010, 34 patients ( ≤ 50 years old) with severe uterine prolapse (prolapse group) who had already given birth and underwent laparoscopic high uterosacral ligament suspension combined with cervical amputation in Peking Union Medical College Hospital were enrolled in this retrospective study. All patients were defined as Pelvic Organ Prolapse Quantification (POP-Q) stage III. Follow-up was performed at 1, 6, and 12 months, and then annually. Anatomic failure was defined as ≥ 1 pelvic compartment classified as POP-Q ≥ stage II.Sexual outcomes were assessed at baseline and 3-year follow-up according to validated Short-Form Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12). Thirty one age-matched women who underwent health examinations during the same time period were selected as a healthy control group. RESULTS: Mean age of women at prolapse group were (39 ± 5) years and average surgery time were (51 ± 8) minutes. No severe intraoperative complications occurred, including urethral twist, bladder and rectum injury, pelvic hemotoma. All patients were followed up for more than 3 years, the mean following up period was 40 months (36-64 months). Based on stage II of POP-Q as recurrence criteria, the anatomical success and patient satisfaction rates were both 100% (34/34). POP-Q point C and D measurements were significantly higher after surgery then those at preoperative values [C:(-5.4 ± 0.6) cm versus (2.2 ± 0.7) cm, D:(-6.7 ± 0.4) cm versus (-4.0 ± 0.7) cm; P < 0.01 for all]. Three years postoperatively, 33 patients were sexually active. Among the 94% (31/33) patients who answered the PISQ-12 questionnaire, there was significant improvement in post- and preoperative total PISQ-12 scores (38 versus 26, P < 0.01) and in all three subscale PISQ-12 domains (P < 0.01 for all). The postoperative PISQ-12 score was similar to that of the control group (38 ± 6 versus 37 ± 3, P > 0.05). CONCLUSION: Laparoscopic high uterosacral ligament suspension combined with cervical amputation conferred satisfying long-term anatomic and sexual function outcomes in women at child-bearing age.

A Novel Five-Step Reduction Technique of Arytenoid Dislocation.

The article reported a novel reduction device and standardized reduction technique for patients with arytenoid dislocation. The results showed that this reduction technique has been excellent in helping patients with arytenoid dislocation. Laryngoscope, 134:1744-1748, 2024.

Trans-cinnamaldehyde fumigation inhibits Escherichia coli by affecting the mechanism of intracellular biological macromolecules.

This study aimed to determine the antibacterial mechanism of cinnamaldehyde fumigation in Escherichia coli (E. coli). Through vapour fumigation, cinnamaldehyde was confirmed to exhibit effective antibacterial activity against E. coli. The minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were 0.25 µL/mL and 0.5 µL/mL, respectively. Based on transmission electron microscopy, the wrinkled bacterial cells observed after fumigation could be related to the leakage of intracellular substances. Laser tweezers Raman spectroscopy revealed changes in the main chain of proteins, the hydrogen bond system and spatial structure, and single- and double-stranded DNA breaks. In addition, breakage of the fatty acyl chain backbone was found to affect the vertical order degree of the lipid bilayer and cell membrane fluidity, thereby inhibiting the growth of E. coli. Overall, our findings indicate that cinnamaldehyde fumigation inhibits E. coli growth by inducing changes in intracellular biological macromolecules.

Comparing urine point-of-care tests to screen preeclampsia: Congo-red dot paper test versus dipstick urinalysis.

To compare the urine Congo-red dot paper test (CRD) with dipstick urinalysis to screen preeclampsia (PE). A total of 409 paired spot urine samples were obtained prospectively from women with suspected pre-eclampsia attending for routine hospital visits. Congo-red dot paper test and dipstick urinalysis were examined and compared to screen pre-eclampsia. The agreement between the two urinary test is modest (kappa coefficient = 0.28, 95% CI 0.14-0.42). The specificity of CRD was higher than urinalysis (97.4% vs. 90.4%, p < .001). Urinalysis performed better in sensitivity (77.3% vs. 40.9%, p = .04) and the area under the receiver operating characteristic curves (AUC) (0.84 [95% CI 0.74-0.94] vs. 0.69 [95% CI 0.55-0.83], p = .04) than CRD, respectively. The sensitivity, specificity, AUC of the parallel test of them is 86.4% (64.0%-96.4%), 89.1% (85.5%-92.0%), and 0.88 (95% CI 0.79-0.96). And the serial test is 31.8% (14.7%-54.9%), 98.7% (96.8%-99.5%), 0.65 (95% CI 0.51-0.79), accordingly. The urinalysis is a better diagnosing test for preeclampsia. CRD could aid in the diagnosis of patients with preeclampsia. Combined the two tests in suspected patients may further improve the performance in the diagnosis of preeclampsia. Further study need to be made for its potential clinical practice.

Enhanced Photostability of Lead Halide Perovskite Nanocrystals with Mn3+ Incorporation.

Recently, lead halide perovskite nanocrystals (NCs) have shown great potential and have been widely studied in lighting and optoelectronic fields. However, the long-term stability of perovskite NCs under irradiation is an important challenge for their application in practice. Mn2+ dopants are mostly proposed as substitutes for the Pb site in perovskite NCs synthesized through the hot-injection method, with the aim of improving both photo- and thermal stability. In this work, we employed a facile ligand-assisted reprecipitate strategy to introduce Mn ions into perovskite lattice, and the results showed that Mn3+ instead of Mn2+, even with a very low level of incorporation of 0.18 mol % as interstitial dopant, can enhance the photostability of perovskite binder film under the ambient conditions without emission change, and the photoluminescent efficiency can retain 70% and be stable under intensive irradiation for 12 h. Besides, Mn3+ incorporation could prolong the photoluminescent decay time by passivating trap defects and modifying the distortion of the lattice, which underscores the significant potential for application as light emitters.

Health-related quality of life and influencing factors of patients with paroxysmal nocturnal hemoglobinuria in China.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder, leading to various complications and impairments in patients' health-related quality of life (HRQOL). Limited research has been conducted to evaluate the HRQOL of Chinese patients with PNH. Understanding the HRQOL in this specific population is crucial for providing effective healthcare interventions and improving patient' health outcomes. This study aimed to assess HRQOL of Chinese patients with PNH, and identify key determinants. METHODS: A cross-sectional study was conducted during 2022 to recruit patients with PNH in China. The study population was recruited from PNH China, one of the largest public welfare PNH patient mutual aid organization in China. Data were collected via an online questionnaire including the EQ-5D-5L (5L), and social-demographic and clinical characteristics. Descriptive statistics were employed to summarize the characteristics of the participants and their HRQOL. Multiple linear and logistic regression analyses were adopted to explore key factors affecting HRQOL. RESULTS: A total of 329 valid questionnaires were collected. The mean (SD) age of the patients was 35.3 (10.0) years, with 52.3% of them being male. The patients reported more problems in Anxiety/Depression (81.5%) and Pain/Discomfort (69.9%) dimensions compared to the other three 5L dimensions. The mean (SD) of 5L health utility score (HUS) and EQ-VAS score were 0.76 (0.21) and 62.61 (19.20), respectively. According to multiple linear regression, initial symptoms (i.e., Anemia [fatigue, tachycardia, shortness of breath, headache] and back pain) and complication of thrombosis were significant influencing factors affecting 5L HUS. Total personal income of the past year, initial symptom of hemoglobinuria and complication of thrombosis were significantly influencing factors of VAS score. Social-demographic and clinical characteristics, such as gender, income, and thrombosis, were also found to be significantly related to certain 5L health problems as well. CONCLUSION: Our study manifested the HRQOL of PNH patients in China was markedly compromised, especially in two mental-health related dimensions, and revealed several socio-demographic and clinical factors of their HRQOL. These findings could be used as empirical evidence for enhancing the HRQOL of PNH patients in China.

Development of a gene knockout system using mobile group II introns (Targetron) and genetic disruption of acid production pathways in Clostridium beijerinckii.

Clostridium beijerinckii is a well-known solvent-producing microorganism with great potential for biofuel and biochemical production. To better understand and improve the biochemical pathway to solvents, the development of genetic tools for engineering C. beijerinckii is highly desired. Based on mobile group II intron technology, a targetron gene knockout system was developed for C. beijerinckii in this study. This system was successfully employed to disrupt acid production pathways in C. beijerinckii, leading to pta (encoding phosphotransacetylase)- and buk (encoding butyrate kinase)-negative mutants. In addition to experimental characterization, the mutant phenotypes were analyzed in the context of our C. beijerinckii genome-scale model. Compared to those of the parental strain (C. beijerinckii 8052), acetate production in the pta mutant was substantially reduced and butyrate production was remarkably increased, while solvent production was dependent on the growth medium. The pta mutant also produced much higher levels of lactate, suggesting that disrupting pta influenced the energy generation and electron flow pathways. In contrast, acetate and butyrate production in the buk mutant was generally similar to that of the wild type, but solvent production was consistently 20 to 30% higher and glucose consumption was more rapid and complete. Our results suggest that the acid and solvent production of C. beijerinckii can be effectively altered by disrupting the acid production pathways. As the gene disruption method developed in this study does not leave any antibiotic marker in a disrupted allele, multiple and high-throughput gene disruption is feasible for elucidating genotype and phenotype relationships in C. beijerinckii.