Salvage endoscopic surgery for skull base osteoradionecrosis in nasopharyngeal carcinoma patients: A prospective, observational, single-arm clinical study.

BACKGROUND: Postradiation skull base osteoradionecrosis (ORN) is a severe complication that occurs after radiotherapy in patients with nasopharyngeal carcinoma (NPC) that can severely affect quality of life (QOL) and be life threatening. Only 13.4% - 28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced salvage endoscopic surgery for skull base ORN patients and evaluated its clinical efficacy. METHODS: This was a prospective, observational, single-arm clinical study. Clinical data from 18 skull base ORN patients who underwent radical endoscopic necrectomy followed by reconstruction using a septal pedicled mucosal flap or temporal muscle flap were included in the study. The endpoint was an overall survival (OS) of 2 years. The numeric rating scale (NRS) scores for pain and foul odor were analyzed to determine the efficacy and safety of this surgery. RESULTS: A total of 21 patients were recruited, 18 of whom completed the study and were analyzed. All surgeries were successfully performed. During the 2-year study, the OS rate of the entire cohort was 75%. The median NRS score for pain decreased from 6.44 +- 2.62 to 0.50 +- 0.71, and the NRS score for foul odor decreased from 1.89±1.08 to 1 after surgery. CONCLUSIONS: Salvage endoscopic necrectomy followed by construction using a septal pedicled mucosal flap or temporal muscle flap is a novel, safe, and effective treatment for ORN in patients with NPC. CLINICAL TRIAL REGISTRATION: This study was approved by the independent ethics committee of the Eye, Ear, Nose and Throat Hospital of Fudan University (IEC No. 2019095-1). Written informed consent was obtained from all patients. The study was registered with the Chinese Clinical Trial registry (ChiCTR2000029327).

[Establishment of contralateral arteriovenous fistula by using the waste vein on the side of central venous lesion: a case report].

Central venous lesion is a difficult problem in the vascular access complications of hemodialysis, which can cause serious clinical symptoms and affect the quality of hemodialysis and life of patients. We established arteriovenous fistula of the contralateral graft blood vessel with the used vein on the diseased side of the central vein of the patient. The arteriovenous fistula of the graft blood vessel was successfully punctured and hemodialysis was performed 2 weeks later. In this way, we not only solved the problem of venous hypertension and subsequent vascular access in the patient, but also reserved more vascular resources.

[The role of Müller cells in the formation and development of macular hole].

Müller cells are important glial cells in the retina, which play important roles in maintaining the stability of the retina by mechanical support, homeostasis, and physiological metabolism, as well as protecting photoreceptor cells and retinal pigment epithelial cells. The degeneration and destruction of Müller cells are often accompanied by various retinal diseases, and the function of Müller cells is changed under pathological conditions. Based on the summary of the morphology, distribution and function of Müller cells, this article analyzes the different manifestations and changes of Müller cells in different stages of macular hole and the closely related mechanisms, aiming to clarify the role of Müller cells in the formation and development of macular hole and to provide reference for the prediction of disease progression and guidance of treatment.(This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on Augest 28, 2023).

[Efficacy and safety of neoadjuvant toripalimab combined with nimotuzumab and chemotherapy in patients with unresectable stage â £ squamous cell carcinoma of penis].

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab in patients with unresectable locally advanced or metastatic squamous cell carcinoma of penis. Methods: A total of 33 patients with unresectable squamous cell carcinoma of penis undergoing neoadjuvant chemotherapy alone or combined with toripalimab and nimotuzumab at Sun Yat-sen University Cancer Center from May 2015 to June 2021 were enrolled retrospectively. All the patients were male, with a median age (M(IQR))of 49.0 (13.5) years (range: 30 to 70 years). According to the therapy protocols, patients were divided into the chemotherapy group (16 cases) and the triple combination group (17 cases). Log-rank test was used to compare the progression-free survival and overall survival. χ2 test or Fisher exact method was used to compare the objective response rate, pathological down-stage rate and adverse events between these two groups. Results: The follow-up time was 28.1(19.2) months (range: 1.5 to 33.4 months). Patients of triple combination group were observed significantly longer progression-free survival (30.0 months vs. 8.2 months, χ²=3.998, P=0.046) than those of chemotherapy group. The median overall survival of the triple combination group and chemotherapy group were not reached and 15.2 months (χ²=3.298, P=0.069), respectively. Although there was no significant difference in the subsequent surgical resection rate between these two groups (12/17 vs.11/16, P=1), the objective response rate and the pathological complete response rate in triple combination group were significantly higher than in chemotherapy group (13/17 vs. 6/16, χ²=5.125, P=0.024; 6/7 vs. 0, P=0.001). The main common grade 1 to 2 adverse events in the triple combination group were alopecia (16 cases), anemia (15 cases), and nausea (14 cases). The main common grade 1 to 2 adverse events in the chemotherapy group were anemia (14 cases), alopecia (12 cases), decreased appetite (12 cases), and nausea (11 cases). The incidence of adverse events ≥grade 3 was similar in the triple combination group and chemotherapy group (8/17 vs. 6/16, χ²=0.308, P=0.579). There was no grade 3 adverse event in both groups. Conclusion: Compared with traditional chemotherapy alone, chemotherapy combined with toripalimab and nimotuzumab provides longer progression-free survival and similar toxicity for unresectable stage Ⅳ squamous cell carcinoma of penis.

[Research progress of autoantibodies in primary biliary cholangitis].

Primary biliary cholangitis (PBC) is a chronic, progressive, intrahepatic cholestasis disease. Its occurrence and development are accompanied by changes in the titer of autoantibodies. However, its pathogenesis, extent of autoantibody changes and their effects are not yet fully understood. Therefore, there is a lack of effective methods for early diagnosis of PBC in patients. Finding specific PBC autoantibody markers will greatly improve the diagnostic efficiency and save early treatment time, thereby improving therapeutic effect and prognosis. This article summarizes several PBC-related serum autoantibody markers.

[Cost-effectiveness of primary prophylaxis with PEG-rhG-CSF in early-stage breast cancer patients receiving chemotherapy in China].

Objective: To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods: Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio (HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion: Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

[Clinical outcomes with cruciate-substituting ultra-congruent and posterior stabilized in total knee arthroplasty].

Objective: To investigate clinical outcomes of total knee arthroplasty with ultra-congruent insert(UC) or posterior stability insert (PS). Methods: A retrospective study was performed on 97 patients (17 males, 80 females, 119 knees) with knee osteoarthritis who received total knee arthroplasty. Of the patients, 42 cases (50 knees) received UC protheses and 55 cases (69 knees) received PS protheses in total knee arthroplasty by the same surgeon in Peking University Third Hospital from March 2015 to November 2015. The data including age, gender, body mass index (BMI), range of motion (ROM), Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Hospital for Special Surgery Knee Score (HSS) before and after the surgery were collected and compared in the two groups. The data were compared between the two groups by single-sample t test. Results: There was no significant differences in age, gender, BMI, ROM, HHS and WOMAC scores between the two groups before operation(all P>0.05). At 3 months and 2 years of follow-up, ROM, HSS and WOMAC scores were significantly improved in the two groups(all P<0.05), but there was no statistical difference between the two groups(t=-0.303, -1.593, Z=-0.500, all P>0.05). One patient with PS prosthesis recieved revision surgery due to prothesis loosening; and no complication found in the UC group(χ(2)=0.731, P>0.05). Conclusion: There is no obvious difference between PS and UC in TKA, UC insert seems to be a practical alternative to the PS.

Evaluation of a loop-mediated isothermal amplification assay based on hrpZ gene for rapid detection and identification of Pseudomonas syringae pv. lachrymans in cucumber leaves.

AIMS: Cucumber angular leaf spot caused by Pseudomonas syringae pv. lachrymans (Psl) is an important and destructive disease worldwide, and no effective technique has been developed for the control of the pathogen. Detection of infection or latent in cucumber plants is critical to evaluate disease progress and strengthening management to avoid a serious epidemic in the fields. In this paper, we developed a rapid and sensitive method for detection of Psl using an isothermal method known as loop-mediated amplification (LAMP). METHODS AND RESULTS: A set of six primers was designed to amplify the gene coding for the hrpZ, and conditions for detection were optimized to complete in 60 min at 67°C, and the amplification were confirmed through gel electrophoresis or visually inspected using calcein stain. The specificity of LAMP primers set was widely validated on Psl and nontarget strains. In sensitivity testing, LAMP allowed detection as low as 104  CFU per ml bacterial cells without DNA extraction. The novel method was also applied for detecting Psl in infected cucumber leaves, and even the early onset of disease can be detected by the assay. CONCLUSIONS: This study confirmed that the novel developed LAMP assay is an easy, rapid and sensitive method for the detection of Psl in infected leaves. SIGNIFICANCE AND IMPACT OF THE STUDY: The method is suitable for direct detection of Psl without strain enrichment and complex DNA extraction from samples in the field, and hence it has the capability to be used for on-site disease diagnosis and field surveys.

[Lung function influenced the prognosis of cardiac surgery in patients with chronic obstructive pulmonary disease].

Objective: To investigate the value of lung function for the prognosis of cardiac surgery in patients with chronic obstructive pulmonary disease(COPD). Methods: A retrospective analysis was conducted on the hospitalized patients with coronary heart disease or valvular heart disease in Beijing Anzhen hospital during Janury 2013 to December 2015. The relationship between lung function and extubation time, time of staying in ICU, second time tracheal incubation, tracheotomy and mortality rate were analyzed. Results: There were 355 patients without surgery in a total 1 729 of patients, of which 65 (18.31%)suffered from severe pulmonary dysfunction. There were 242 patients with obstructive ventilation dysfunction, 75 with mild, 127 with moderate, and 40 with severe and very severe obstructive ventilation dysfunction. There were significant differences in the rates of planned extubation and late extubation between patients with normal lung function (81.6% and 10.7%) and those with abnormal lung function(74.4% and 12.8%). In patients with different GOLD classification (Ⅰ, Ⅱ, and Ⅲ-Ⅳ), there were significant differences in the rates of early extubation 14.7%, 14.2% and 5%, planned extubation (80%, 74% and 65%) and late extubation (5.3%, 11.8% and 30%). By comparison with patients without COPD, the extubation time of COPD patients increased by 20.3%, the time of staying in ICU prolonged by 14.2%, and the mortality rate increased to 180%(P<0.05). However, there was no significant difference in the rate of second time tracheal incubation or tracheotomy. Conclusion: There was a close relationship between GOLD classification and prognosis of cardiac surgery patients with COPD. Cardiac surgery needs to be cautious because of increase in incidence of postoperative adverse events in patients with severe pulmonary dysfunction.

Evaluation of bone matrix gelatin/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering.

This study was designed to evaluate bone matrix gelatin (BMG)/fibrin glue and chitosan/gelatin composite scaffolds for cartilage tissue engineering. Chondrocytes were isolated from costal cartilage of Sprague-Dawley rats and seeded on BMG/fibrin glue or chitosan/gelatin composite scaffolds. After different in vitro culture durations, the scaffolds were subjected to hematoxylin and eosin, Masson's trichrome, and toluidine blue staining, anti-collagen II and anti-aggrecan immunohistochemistry, and scanning electronic microscopy (SEM) analysis. After 2 weeks of culture, chondrocytes were distributed evenly on the surfaces of both scaffolds. Cell numbers and the presence of extracellular matrix components were markedly increased after 8 weeks of culture, and to a greater extent on the chitosan/gelatin scaffold. The BMG/fibrin glue scaffold showed signs of degradation after 8 weeks. Immunofluorescence analysis confirmed higher levels of collagen II and aggrecan using the chitosan/gelatin scaffold. SEM revealed that the majority of cells on the surface of the BMG/fibrin glue scaffold demonstrated a round morphology, while those in the chitosan/gelatin group had a spindle-like shape, with pseudopodia. Chitosan/gelatin scaffolds appear to be superior to BMG/ fibrin glue constructs in supporting chondrocyte attachment, proliferation, and biosynthesis of cartilaginous matrix components.

Telomere-associated factor expression in replicative senescence of human embryonic lung fibroblasts.

The objective of this study was to find the key regulatory molecules in the cell senescence process through observing the expression of telomere-associated factor during the normal cell replicative senescence process. Based on the established cell replicative senescence model, reverse transcription-polymerase chain reaction and western blot analyses were used to detect telomere-associated factor expression at the mRNA and protein levels, including that of human telomere binding protein 1, tankyrase 1, telomerase RNA, telomere protection protein 1 (POT1), and p53 during the process of human embryonic lung fibroblast replicative senescence. The results showed that transcription of human telomere binding protein 1 did not change with cell senescence, whereas the protein expression of human telomere binding protein 1 increased gradually and then decreased rapidly; there was no change in the mRNA and protein expression of POT1; with the replicative senescence of human embryonic lung fibroblasts, expression of POT1 decreased gradually; TRF1 showed an increasing trend with cell senescence; and p53 protein expression did not change. Together, the results from this study suggest that human telomere binding protein 1, POT1, and TRF1 played important roles in cell senescence.

First Report of Pseudomonas cichorii Causing Leaf Spot of Vegetable Sponge Gourd in China.

A suspect bacterial leaf spot on vegetable sponge gourd (Luffa cylindrical (L.) Roem.) was found in a commercial greenhouse in Pi County, Chengdu City, Sichuan Province, China, in February 2011. Approximately 20 to 30% of plants were affected, causing serious economic loss. Symptoms occurred only on seedlings and consisted of water-soaked, irregularly shaped, black lesions on the surface and margins of cotyledons. A bacterium was consistently isolated on nutrient agar from diseased leaf tissues that had been surface disinfected in 70% ethyl alcohol for 30 s. The bacterium produced small gray colonies with smooth margins, was gram negative, fluoresced on King's B medium, and showed pectolytic activity when inoculated on potato slices. The partial sequences of 16SrRNA gene (1,377 bp) of the bacterium (GenBank Accession No. KC762217), amplified by using universal PCR primers 16SF (5'-AGAGTTTGATCCTGGCTCAG-3') and 16SR (5'-GGTTACCTTGTTACGACTT-3'), shared 100% similarity with that of Pseudomonas cichorii (GenBank Accession No. HM190228). The vegetable sponge gourd isolate was also identified by using the Biolog Microbial Identification System (version 4.2, Biolog Inc., Hayward, CA) as P. cichorii with the following characteristics (1): negative for arginine dihydrolase, gelatin liquefaction, and N2 production. Positive reactions were obtained in tests for catalase, oxidase, potato rot, utilization of melibiose, and mannitol. Tests were negative for utilization of sucrose, trehalose, D-arabinose, raffinose, cellobiose, and rhamnose. A pathogenicity test was conducted on 4-week-old vegetable sponge gourd plants by spray-inoculation with 108 CFU/ml sterile distilled water on the leaves of 15 vegetable sponge gourd plants and by needle puncture on the stems of 15 other plants with P. cichorii, respectively. Control plants were misted with sterile distilled water or punctured on the stem with a clean needle. Plants were placed in a greenhouse maintained at 28 ± 2°C with relative humidity of 80 to 85%. Symptoms, the same as seen on the original diseased plants, developed after 7 to 10 days on inoculated plants. Control plants remained healthy. The bacterium was readily re-isolated from inoculated plants and identified as P. cichorii using P. cichorii-specific primer hrpla/hrp2a (1). To our knowledge, this is the first report of P. cichorii causing disease on commercially grown vegetable sponge gourd in China. This new finding will provide the basis for developing resources for diagnostics and management, including screening varieties for resistance. References: (1) S. Mazurier et al. J. FEMS Microbiol. Ecol. 49:455, 2004. (2) N. W. Schaad et al., eds. Laboratory Guide for Identification of Plant Pathogenic Bacteria, 3rd ed. APS Press, St. Paul, MN, 2001.

First Report of Myrothecium roridum Causing Leaf Spot on Zantedeschia aethiopica in China.

Zantedeschia aethiopica (L.) Spreng. (calla lily), belonging to family Araceae, is a popular ornamental plant in China. In the summer of 2010, leaves of calla lily with typical symptoms of necrotic lesions were observed in a commercial glasshouse in Beijing, China (116°20' E, 39°44' N). The initial symptoms were circular to subcircular, 1 to 3 mm, and dark brown lesions on the leaf lamina. Under high humidity, lesions expanded rapidly to 5 to 10 mm with distinct concentric zones and produced black sporodochia, especially on the backs of leaves. Later, the infected leaves were developing a combination of leaf lesions, yellowing, and falling off; as a result, the aesthetic value of the plant was significantly impacted. Leaf samples were used in pathogen isolation. Symptomatic leaf tissues were cut into small pieces and surface sterilized with 70% ethanol for 30 s and then in 0.1% mercuric chloride solution for 1 to 3 min. After being washed in sterile distilled water three times, the pieces were plated on potato dextrose agar (PDA) and incubated at 25°C in darkness for 7 days (5). Initial colonies of isolates were white, floccose mycelium and developed dark green to black concentric rings that were sporodochia bearing viscid spore masses after incubating 5 days. Conidiophores branched repeatedly. Conidiogenous cells were hyaline, clavate, and 10.0 to 16.0 × 1.4 to 2.0 µm. Conidia were hyaline, cylindrical, both rounded ends, and 6.0 to 8.2 × 1.9 to 2.4 µm. Morphological characteristics of the fungus were consistent with the description of Myrothecium roridum Tode ex Fr. (3,4). To confirm the pathogenicity, three healthy plants of calla lily were inoculated with a conidial suspension (1 × 106 conidia per ml) brushed from a 7-day-old culture of the fungus. Control plants were sprayed with sterile water. The inoculated plants were individual with clear plastic bags and placed in a glass cabinet at 25°C. After 7 days, all inoculated leaves developed symptoms similar to the original samples, but control plants remained disease free. Re-isolation and identification confirmed Koch's postulates. For molecular identification, genomic DNA of a representative isolate (MTL07081001) was extracted by modified CTAB method (1), and the rDNA-ITS region was amplified by using primers ITS1 (5-TCCGTAGGTGAACCTGCGG-3) and ITS4 (5-TCCTCCGCTTATTGATATGC-3). The 465-bp amplicon (GenBank Accession No. KF761293) was 100% identity to the sequence of M. roridum (JF724158.1) from GenBank. M. roridum has an extensive host range, covering 294 host plants (2). To our knowledge, this is the first record of leaf spot caused by M. roridum on calla lily in China. References: (1) F. M. Ausubel et al. Current Protocols in Molecular Biology. John Wiley & Sons Inc, New York, 1994. (2) D. F. Farr and A. Y. Rossman, Fungal Databases. Syst. Mycol. Microbiol. Lab., ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , October 2013. (3) M. T. Mmbaga et al. Plant Dis. 94:1266, 2010. (4) Y. X. Zhang et al. Plant Dis. 95:1030, 2011. (5) L. Zhu et al. J. Phytopathol. 161:59, 2013.

Synthesis of novel silver-loaded clay AgF@Hec for the prevention of dental cariesin vitro.

Dental caries, a chronic infectious disease characterized by tooth mineral loss caused by plaque, is one of the major global public health problems. Silver diamine fluoride (SDF) has been proven to be a highly effective anti-caries drug due to its high bacterial inhibition and remineralization ability. However, the SDF solution is unstable, which immensely limits its clinical application. Therefore, new silver-load clay named AgF@Hec was designed by replacing the NH3with hectorite in this study. Fourier transform infrared spectroscopy and x-ray diffraction spectroscopy were employed to confirm the structure of AgF@Hec. Dynamic light scattering analysis was used to reveal the effect of different hectorite concentrations on the stability of AgF@Hec. Moreover, AgF@Hec exhibits significant remineralization and hardness recovery of the initial carious lesions. Bacteriostatic experiments also proved that it has a significant inhibitory effect onA. Viscosus, S. mutans, S. sanguinis, S. salivarius, Lactobacillus sp.and both gram-positive and gram-negative bacteria. We therefore believed that AgF@Hec should be a promising biomaterial that can be applied in the prevention of dental caries.