[Comparison of the efficacy of carelizumab combined with chemotherapy and chemotherapy alone in the induction therapy of locally advanced hypopharyngeal carcinoma].

Objective: To compare the efficacy and safety of carrelizumab combined with the modified TPF regimen (docetaxel, cisplatinand capecitabine) and TPF regimen alone in larynx preservation strategy for locally advanced resectable hypopharyngeal squamous cell carcinoma. Methods: A cohort study was conducted. Patients with locally advanced resectable hypopharyngeal carcinoma (cT3-4aN0-3bM0) who were treated at the Eye & ENT Hospital of Fudan University from January 2017 to April 2023 were enrolled in the study. One group was treated with a modified TPF regimen (TPF group) for 2-3 cycles (retrospective data), and the other group was a prospective phase Ⅱ trial with a modified TPF regimen combined with carrelizumab (TPFC group) for three cycles. The patients with complete or partial remission of the primary focus were treated with sequential radical radiotherapy and/or drug therapy. The patients in the TPFC group were treated with carrelizumab at the end of radiotherapy with a maximum of up to 18 doses. The patients with stable or progressive disease were given radical surgery, and those who refused the surgery were given radical chemoradiotherapy. Objective response rate (ORR), overall survival rate, progression-free survival (PFS) rate, larynx preservation rate (LPR), and adverse reactions were compared between the two groups. Results: There were 51 male patients in the TPFC group, with an median age of 57 (35, 69) years. Meanwhile, 44 patients were in the TPF group, among which 43 were male and one was female, with an median age of 62 (46, 70) years. The ORR of the TPFC group was higher than that of the TPF group [82.4% (42/51) vs 63.6% (28/44), P=0.039]. During a median follow-up of 24.4 (18.5, 31.4) months, the TPFC group showed a higher 2-year survival rate (84.8% vs 64.6%, P=0.013) and 2-year LPR (66.6% vs 48.6%, P=0.045) than those in the TPF group. In patients with poor effect of induction therapy for hypopharyngeal carcinoma, surgical combination therapy significantly prolonged the 2-year PFS rate (77.9% vs 18.2%, P<0.001) and 2-year survival rate (76.9% vs 45.5%, P=0.005)than those of non-surgical combination therapy. The incidences of nausea and/or vomiting, reactive cutaneous capillary endothelial proliferation, thyroid dysfunction, and rash were increased in the TPFC group (all P<0.05). There was no treatment-related death. Conclusion: Carrelizumab combined with a modified TPF regimen has good efficacy and safety and can improve the LPR of locally advanced hypopharyngeal carcinoma.

[Association between ambient air pollution and biological aging among the middle-aged and older adults: a systematic review].

Objective: To summarize and elucidate the impact of ambient air pollution on biological aging among middle-aged and older adults. Methods: "Air pollution""Biological age""Epigenetic age""Biological aging"and"Epigenetic aging", as well as specific names of air pollutants and biological age were used as search keywords. This study searched the databases of PubMed and Web of Science for eligible English articles and CNKI, CQVIP, Wanfang, CBM, CSTP and other Chinese databases for eligible Chinese articles from inception until June 30, 2023. The language was limited to Chinese and English. Results: Among the 14 included articles, five studies investigated the impact of air pollution on DNA methylation age using different algorithms, while six studies explored the relationship between air pollutants and telomere length. Six studies focused on frailty as an outcome, and an additional study revealed the relationship between fine particulate matter (PM2.5) and its components with composite indicator age (KDM age). The results indicated that, although different forms of biological ages were susceptible to different ambient air pollutants at different degrees, previous studies had consistently found that the increased levels of PM2.5 and one of its major components, black carbon (BC), could significantly accelerate the biological aging of middle-aged and older adults. Similar trends were observed with nitrogen oxides (NOx) and ozone (O3) but with relatively limited evidence. Conclusion: Major air pollutants could accelerate the biological aging of middle-aged and older adults.

[The mechanism of NRF2 inhibiting ROS induced autophagy to reduce ovarian granulosa cells damage].

This study explores the effects and possible mechanisms of nuclear factor E2 related factor 2 (NRF2) on ovarian granulosa cells, providing a scientific basis to prevent premature ovarian failure. An ovarian cell injury model was constructed by treating human ovarian granulosa cell (KGN cell) with 4-Vinylcyclohexene dioxide (VCD). Firstly, KGN cells were treated with different concentrations of VCD, and cell counting kit 8 (CCK-8) was used to detect ovarian cell proliferation. After determining IC50 by CCK8, the levels of estradiol and progesterone in the cell supernatant were detected using enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) assay kit was used to detect the content of ROS in ovarian cells, real-time fluorescence quantitative polymerase chain reaction (qRT PCR) was used to detect the mRNA expression level of NRF2, and Western blot was used to detect the protein expression level of NRF2. Further, NRF2 silence (siNRF2) and overexpression (NRF2-OE) cell models were constructed through lentivirus transfection, and the effects of regulating NRF2 on VCD treated cell models were investigated by detecting hormone levels, oxidative stress indicators (ROS, SOD, GSH-Px), and autophagy (LC3B level). The results showed that VCD intervention inhibited the proliferation of ovarian granulosa cells in a time-dependent and dose-dependent manner (F>100, P<0.05), with an IC50 of 1.2 mmol/L at 24 hours. After VCD treatment, the level of estradiol in the cell supernatant decreased from (56.32±10.18) ng/ml to (24.59±8.75) ng/ml (t=5.78, P<0.05). Progesterone decreased from (50.25±7.03) ng/ml to (25.13±6.67) ng/ml (t=6.54, P<0.05). After VCD treatment, the SOD of cells decreased from (44.47±7.71) ng/ml to (30.92±4.97) ng/ml (t=3.61, P<0.05). GSH-Px decreased from (68.51±10.17) ng/ml to (35.19±6.59) ng/ml (t=5.73, P<0.05). Simultaneously accompanied by an increase in autophagy and a decrease in NRF2. This study successfully constructed KGN cell models that silenced NRF2 and overexpressed NRF2. Subsequently, this study treated each group of cells with VCD and found that the cell proliferation activity of the siNRF2 group was significantly reduced (t=8.37, P<0.05), while NRF2-OE could reverse the cell activity damage caused by VCD (t=3.37, P<0.05). The siNRF2 group had the lowest level of estradiol (t=5.78, P<0.05), while NRF2-OE could reverse the decrease in cellular estradiol levels caused by VCD (t=5.58, P<0.05). The siNRF2 group had the lowest progesterone levels (t=3.02, P<0.05), while NRF2-OE could reverse the decrease in cellular progesterone levels caused by VCD (t=2.41, P<0.05). The ROS level in the siNRF2 group was the highest (t=2.86, P<0.05), NRF2-OE could reverse the increase in ROS caused by VCD (t=3.14, P<0.05), the SOD enzyme content in the siNRF2 group was the lowest (t=2.98, P<0.05), and NRF2-OE could reverse the decrease in SOD enzyme content caused by VCD (t=4.72, P<0.05). The GSH-Px enzyme content in the siNRF2 group was the lowest (t=3.67, P<0.05), and NRF2-OE could reverse the decrease in antioxidant enzyme content caused by VCD (t=2.71, P<0.05). The LC3B level was highest in the siNRF2 group (t=2.45, P<0.05), and NRF2-OE was able to reverse the LC3B elevation caused by VCD (t=9.64, P<0.05). In conclusion, NRF2 inhibits ROS induced autophagy, thereby playing a role in reducing ovarian granulosa cell damage, which may be a potential target for premature ovarian failure.

[The effectiveness and safety of the anti gastroesophageal reflux system in the treatment of gastroesophageal reflux disease: a single center study of 23 cases].

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged (M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) (κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) (κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Risk prediction of second primary malignancies in primary colorectal neuroendocrine neoplasms patients: a population-based study.

PURPOSE: In this study, we aimed to identify risk factors for developing second primary malignancies (SPMs) in colorectal neuroendocrine neoplasms (NENs) patients and develop a competing-risk nomogram to predict SPMs' probabilities quantitatively. METHODS: Patients with colorectal NENs were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database during 2000-2013. Potential risk factors for SPMs' occurrence in colorectal NENs' patients were identified by the Fine and Gray's proportional sub-distribution hazards model. Then, a competing-risk nomogram was constructed to quantify SPMs' probabilities. The discriminative abilities and calibrations of this competing-risk nomogram were assessed by the area under the receiver-operating characteristic (ROC) curves (AUC) and calibration curves. RESULTS: We identified 11,017 colorectal NENs' patients, and randomly divided them into training (n = 7711 patients) and validation (n = 3306 patients) cohorts. In the whole cohort, 12.4% patients (n = 1369) had developed SPMs during the maximum follow-up of approximately 19 years (median 8.9 years). Sex, age, race, primary tumor location, and chemotherapy were identified as risk factors for SPMs' occurrence in colorectal NENs' patients. Such factors were selected to develop a competing-risk nomogram and showed excellent predictive ability for SPMs' occurrence (the 3-, 5-, and 10-year AUC values were 0.631, 0.632, and 0.629 in the training cohort and 0.665, 0.639, 0.624 in the validation cohort, respectively). CONCLUSIONS: This research identified risk factors for SPMs' occurrence in colorectal NENs' patients. Competing-risk nomogram was constructed and proved to have good performance.

[Validation of calculation method for dose distribution around radioactive iodine-125 particles based on AAPM TG43 report].

Objective: According to the formula provided by the TG43 report [AAPM TG43 (2004)] proposed by the American Association of Physicists in Medicine (AAPM) in 2004, we calculated the dose distribution around the radioactive iodine-125 particles, and verified the calculation accuracy of the radioactive iodine-125 particles treatment planning system. Methods: AAPM TG43 (2004) report provides two calculation methods when calculating the dose around a single radioactive source. The calculation method that does not consider the geometric structure of the radioactive source is called point source calculation method, and the calculation method that considers the geometric structure of the radioactive source is called line source calculation method. Assuming a single Amersham 6711 radioactive iodine-125 particle with an activity of 100 U, the following point doses were calculated according to the two calculation methods provided by AAPM TG43 (2004) report, at 0°, 90° directions, distances 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 and 6 cm; In the direction of 45°, the doses at 0.71, 1.41, 2.12, 2.83, 3.54, 4.24, 4.95, 5.66, 6.36, 7.07, 7.78 and 8.49 cm. On the clinically used brachytherapy planning system variseeds 8.0, the above two calculation methods are used to calculate the corresponding activity and the dose around the corresponding type of radioactive iodine-125 particles, and the function of capturing points to templates built in the planning system is used to accurately find the above corresponding point position, using a single measurement of the above corresponding point dose; and comparation of the results were performed to see if there is a statistical difference. Results: The AAPM TG43 report uses point source calculation method to calculate the dose of single Amersham 6711 radioactive iodine-125 particles with activity of 100 U at 0° and 90° directions. The points with the same distance and the same dose are 8 082.18, 1 870.08, 756.58, 381.47, 217.11, 131.91, 86.55, 58.32, 39.97, 27.42, 19.74, 14.13 Gy, respectively, at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5 and 6 cm away from them. In the 45° direction, the doses at the distances of 0.71, 1.41, 2.12, 2.83, 3.54, 4.24, 4.95, 5.66, 6.36, 7.07, 7.78 and 8.49 cm are 3 957.37, 865.83, 329.99, 155.69, 84.10, 48.50, 28.49, 17.80, 11.37, 7.38, 4.98 and 3.39 Gy, respectively; For line source calculation method, radioactive particles are at the same distance as above. The doses at each point in the direction of 0° are 3 128.71, 755.44, 330.30, 180.53, 107.74, 68.56, 46.40, 32.22, 22.70, 16.00, 11.51, 8.24 Gy, respectively. The doses at each point in the direction of 90° are 8 306.46, 1 981.01, 802.74, 405.38, 230.60, 140.03, 91.83, 61.84, 42.36, 29.05, 20.91, 14.97 Gy; In the 45° direction, the dose at the corresponding distance as above is 4 020.78, 877.43, 333.49, 156.93, 84.69, 48.81, 28.65, 17.89, 11.42, 7.41, 4.99 and 3.40 Gy, respectively. The maximum dose difference (0.3%) between the two methods is 7.78 cm in the 45° direction, the maximum difference (-0.3%) between the two methods is 8.49 cm in the 45° direction, and the value of other sampling points is less than 0.3%. The closer the Amersham 6711 iodine-125 particles are to the source in the directions of 0°, 45°, and 90°, the faster the dose will drop, and the dose will drop gradually as the distance increases. Conclusion: The brachytherapy planning system variseeds 8.0 and the AAPM TG43 report calculate a maximum dose difference of 0.3%, which can accurately calculate the dose distribution around radioactive iodine-125 seeds, and provide a reliable tool for the clinical implementation of radioactive iodine-125 particles implantation for tumor treatment.

[Clinicopathological characteristics of Klinefelter syndrome: a testicular biopsy analysis of 87 cases].

Objective: To investigate the clinicopathological characteristics of testicular biopsies from Klinefelter syndrome (KS) patients. Methods: The testicular biopsy specimens of 87 patients with KS (a total of 107 biopsy specimens) were collected from the Department of Pathology, Peking University Third Hospital, Beijing, China from January 2017 to July 2022. All patients were diagnosed as KS by peripheral blood karyotyping analysis. The testicular histopathologic features, testicular volume and hormone levels were evaluated retrospectively. The histopathologic analysis was used to assess the quantity and morphology of Leydig cells, the spermatogenic state of seminiferous tubules, the thickening of the basement membrane of seminiferous tubules and the changes of stroma. Results: Leydig cell proliferative nodules were seen in 95.3% (102/107) of KS testicular biopsy tissues. The eosinophilic inclusion bodies and lipofuscin in Leydig cells were found in 52.3% (56/107) and 57.9% (62/107) of specimens, respectively. The Sertoli cell only seminiferous tubules and the hyalinized tubules were found in 66.4% (71/107) and 76.6% (82/107) of the examined tissues, respectively. The tubules with complete spermatogenic arrest were found in 15.9% (17/107) of specimens, and 5.6% (6/107) of the specimens showed low spermatogenesis or incomplete spermatogenic arrest. In 85.0% (91/107) of the specimens, increased thick-walled small vessels with hyaline degeneration were identified. Conclusions: The most common features of KS testicular specimens are Leydig cell proliferative nodules, hyaline degeneration of seminiferous tubules and proliferation of thick-walled blood vessels. Testicular biopsy specimens of KS are rare. The pathologists can make a tentative diagnosis of KS based on the histological findings, combined with the ultrasound and laboratory results, which is helpful for further diagnosis and treatment of KS.

[Seasonal variations influenced the semen quality of the sperm donor in Beijing area].

OBJECTIVE: To investigate the change trends of sperm quality with seasonal variations among the volunteers of sperm donors in Beijing area, as well as the relationship between two parameters. METHODS: Semen data from the volunteers of sperm donors in Human Sperm Bank of Peking University Third Hospital were collected using a retrospective study method. The subjects were divided into 4 seasonal groups based on the lunar solar terms and the time of sperm donation. The data were assessed to find whether there were differences in semen parameters among different seasonal groups, and to analyze the change trends and the influence of seasonal factors on semen parameters. RESULTS: A total of 21 174 semen parameter data were analyzed. Firstly, to analyze all data as a whole, in spring, summer, autumn and winter groups, sperm concentration was (106.04±59.67)×106/mL, (97.61±47.41)×106/mL, (100.18±47.17)×106/mL, (100.59±38.68)×106/mL, respectively, and the spring group was significantly higher than the other 3 seasonal groups (P < 0.001); proportion of progressive motility sperm (PR) was 56.49%±12.76%, 58.02%±13.65%, 58.05%±12.36%, and 57.66%±12.61%, respectively, spring group was lower than the other three seasonal groups, and summer group was better among the latter (P < 0.001). There was no difference in normal rate of sperm morphology among the four seasonal groups. The qualified rate of sperm donors in the winter group was higher than that in the other three seasons groups (P < 0.01), while the qualified rate in the summer group was lower than that in the other three seasons groups. In addition, the semen parameters of the volunteers during the screening period and the official sperm donation period were analyzed respectively, which revealed that sperm concentration of spring group was higher than that of summer and winter groups, and PR was lower than that of summer and autumn groups. On account of the semen parameters of official sperm donation period, multiple linear regression analysis found that season was the main factor affecting sperm concentration, the average sperm concentration in spring group was about 6×106/mL higher than in winter group, but PR was 2.9% lower in spring group compared with autumn group (all P < 0.05). CONCLUSION: Season was the influencing factor of semen quality of sperm donors in Beijing area. We recommend spring and winter may be the preferred seasons for sperm donation.

Identification and Verification of the Ability of Cdk5 to Phosphorylate Deubiquitinating Enzyme BRCC3 In Vitro.

It is known that the expression of the deubiquitinating enzyme BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and cyclin-dependent protein kinase 5 (Cdk5) is increased in Parkinson's disease (both are involved in neuroinflammatory response). However, the regulatory mechanism of Cdk5 on the post-translational modification of BRCC3 remains unclear. Here we studied whether Cdk5 phosphorylates BRCC3. Phosphorylation of BRCC3 by Cdk5 was predicted by GPS 5.0 software. His-BRCC3 plasmid was constructed by cloning the BRCC3 gene into pGEX-6P-1 vector, and then His-BRCC3 fusion protein was induced with isopropyl ß-d-1-thiogalactopyranoside and purified using His-Tag affinity chromatography purification agarose. Phosphorylation of BRCC3 fusion protein by Cdk5 in vitro was detected by mass spectrometry and Western blotting. The results showed that multiple phosphorylation sites were predicted by GPS 5.0, and the His-BRCC3 fusion protein was successfully induced and purified. In vitro kinase assay, Western blotting, and mass spectrometry showed that Cdk5 can phosphorylate BRCC3. It has been demonstrated that protein kinase Cdk5 can phosphorylate the deubiquitinating enzyme BRCC3 in vitro, which provides new data for further study on the mechanism of neurodegeneration.

[Long-term outcome follow-up of Oxford unicompartmental knee arthroplasty for medial compartment osteoarthropathy:a single center's experience for 10 years].

Objective: To investigate the long-term outcomes of minimally invasive Oxford phase Ⅲ unicompartmental knee arthroplasty (UKA) for patients with medial compartment osteoarthropathy. Methods: The clinical data of 594 patients (701 knees) who underwent minimally invasive UKA with Oxford phase Ⅲ unicompartmental prosthesis at Department of Orthopedics,the Affiliated Hospital of Qingdao University from January 2007 to January 2016 were retrospectively analyzed.There were 155 males and 439 females,aged (62.6±10.9) years (range: 44 to 81 years),with a body mass index of (26.9±3.8) kg/m2 (range: 21.1 to 36.2 kg/m2).There were 359 left knees and 342 right knees,676 knees with osteoarthritis and 25 knees with idiopathic osteonecrosis of the medial femoral condyle.There were 487 cases underwent UKA (66 cases underwent UKA on one side and total knee arthroplasty on the other) and 107 cases underwent bilateral UKA.Patients' prosthetic survival,complications,range of motion(ROM) of the knee,visual analogue score (VAS),Western Ontario and McMaster University (WOMAC) osteoarthritis index,and American knee society score (KSS) were collected to assess clinical outcomes.Paired sample t test was used to compare the data before and after operation. Results: All patients completed the surgery successfully.There was no intraoperative fractures,postoperative infections or symptomatic vascular embolic disease occurred.The postoperative complications,including mobile bearing dislocation,prosthesis loosening,tibial plateau collapse,the lateral compartment degeneration and postoperative pain were occurred in 18 cases (3.0%,18/594).Thirteen patients suffered complications were transferred to total knee arthroplasty,4 underwent partial revision,if this was used as the endpoint of the study,the surgical success rate was 97.1% (577/594) and the prosthetic revision rate was 2.9%.The ROM was improved from(105.9±11.8)°preoperatively to (114.0±13.3)° at the last follow-up (t=10.796,P<0.01);the KSS clinical score was increased from 54.3±3.6 to 90.1±6.0 (P<0.01) and the functional score was increased from 55.9±3.9 to 87.5±5.7(t=124.325,P<0.01;t=110.985,P<0.01).The WOMAC osteoarthritis index was decreased from 54.8±6.7 to 9.2±3.1 at the last follow-up(t=150.860,P<0.01) and the VAS was decreased from 6.1±1.1 to 1.5±1.0 at the last follow-up(t=74.941,P<0.01). Conclusions: Minimally invasive Oxford phase Ⅲ UKA for medial compartment knee osteoarthritis has a favorable prosthesis survival rate,low revision rate,and few complications at long-term follow-up.Patients have significant improvement in knee function with satisfactory clinical outcomes.

Diffusion-tensor imaging for differentiating uterine sarcoma from degenerative uterine fibroids.

AIM: To explore the applicability of diffusion-tensor imaging (DTI) sequence quantitative parameters in differentiating uterine sarcoma (USr) from degenerative uterine fibroids (DUF). MATERIALS AND METHODS: Fourteen cases of USr and 30 cases of DUF were analysed retrospectively. The diffusion-weighted imaging (DWI) and DTI images were analysed by two observers using Functool software on a ADW4.6 workstation. The images were post-processed to generate an apparent diffusion coefficient (ADC) map of DWI, ADC map of DTI (ADCT map), and fractional anisotropy (FA) map. Three regions of interest (ROI) were selected from the ADC, ADCT, and FA maps to obtain the ADC, ADCT, and FA values. The receiver operating characteristic (ROC) curves of all parameters were used to analyse and compare the diagnostic value of USr and DUF. RESULTS: The ADC value, ADCT value, and FA value of USr (1.190 ± 0.262 × 10-3mm2/s, 1.165 ± 0.270 × 10-9mm2/s, 0.168 ± 0.063) were significantly lower compared to the values for DUF (1.525 ± 0.314 × 10-3mm2/s, 1.650 ± 0.332 × 10-9mm2/s, 0.254 ± 0.111; all p<0.001). The diagnostic threshold values for USr were: ADC ≤1.290 × 10-3mm2/s, ADCT ≤1.322 × 10-9mm2/s and FA ≤0.192. The corresponding sensitivities and specificities were 78.6%/90%, 96.7%/92.9%, and 86.7%/85.7%, respectively. The areas under the curve (AUC) were 0.875, 0.974, and 0.831, respectively. CONCLUSIONS: DTI quantitative parameters can be used to differentiate USr from DUF. The ADCT value had the highest diagnostic efficacy.

Production and purification of 2-phenylethanol by Saccharomyces cerevisiae using tobacco waste extract as a substrate.

2-phenylethanol (2-PE), which is extracted naturally from plant or biotechnology processing, is widely used in the food and cosmetics industries. Due to the high cost of 2-PE production, the valorization of waste carbon to produce 2-PE has gained increasing attention. Here, 2-PE was produced by Saccharomyces cerevisiae using tobacco waste extract (TWE) as the substrate. Considering the toxicity of nicotine and its inhibition of 2-PE, the tolerance of S. cerevisiae was first evaluated. The results suggested that the production of 2-PE by S. cerevisiae in TWEs could be carried out at 2·0 mg ml-1 nicotine concentrations and may be inhibited by 1·0 mg ml-1 2-PE. Thus, the compounds in the TWEs prepared at different temperatures were detected, and the results revealed that the TWEs prepared at 140°C contained 2·18 mg ml-1 of nicotine, had total sugar concentrations of 26·8 mg ml-1 and were suitable for 2-PE production. Due to feedback regulation, the 2-PE production was only 1·11 mg ml-1 , and the remaining glucose concentration remained at 13·78 mg ml-1 , which indicated insufficient glucose utilization. Then, in situ product recovery was further implemented to remove this inhibition; the glucose utilization (the remaining concentration decreased to 3·64 mg ml-1 ) increased, and the 2-PE production increased to 1·65 mg ml-1 . The 2-PE produced in the fermentation broth was first isolated by elution from the resin with 75% ethanol and then by removing the impurities with 2·5% activated charcoal, and pure 2-PE was identified by gas chromatography mass spectrometry. The results of this study suggest that TWE could be an alternative carbon source for 2-PE production. This could provide an outlet tobacco waste as well as reducing the price of natural 2-PE, although more strategies need to be explored to improve the production yield of 2-PE by using TWE.

[Predictive value of neutrophil-lymphocyte ratio on admission and before discharge for long-term all-cause death in hospitalized heart failure patients with reduced ejection fraction].

Objective: To evaluate the predictive value of neutrophil-lymphocyte ratio (NLR) on admission and before discharge for long-term all-cause death (ACD) in patients hospitalized with heart failure with reduced ejection fraction (HFrEF). Methods: Patients hospitalized and discharged from hospital alive with the clinical diagnosis of HFrEF in cardiac care unit (CCU) of TEDA International Cardiovascular Hospital from January 2013 to December 2017 were consecutively enrolled. NLR, which was defined as neutrophil counts divided by lymphocyte counts, was measured 1 day within admission and 3 days before discharge to evaluate the prognostic value of admission NLR in combination with discharge NLR for the ACD after discharge by using of multivariate Cox regression analysis. Patients were followed-up until December 2020 or ACD. Results: A total of 368 patients hospitalized with HFrEF were enrolled with an age of (54±14) years, including 79 females (21.5%). During the median (inter-quartile range, IQR) duration of follow-up after discharge of 30 (10, 60) months, 95 patients died, thus, the rate of ACD was 25.8%. Multivariate Cox regression analysis showed that the NLR level before discharge was an independent predictor of ACD after discharge [hazard ratio (HR)=1.143, 95% confidence interval (CI) 1.048-1.248, P=0.003] after adjusting for other parameters such as systolic blood pressure on admission and at discharge, left ventricular end-diastolic diameter on admission, and usage of aldosterone receptor blockers at discharge. Moreover, compared to those with NLR level at admission ≤2.25 and ≤2.00 before discharge, the long-term risk of ACD after discharge was nearly doubled for patients with NLR level at admission>2.25 and>2.00 before discharge (adjusted HR=1.968, 95%CI 1.198-3.234, P=0.008). Conclusions: The NLR level before discharge was an independent predictor of ACD after discharge for patients hospitalized with HFrEF. Combining NLR levels at admission and before discharge help to better predictive the risk of long-term ACD after discharge.

[Effect of laparoscopic novel W-H fundoplication in patients with proton pump inhibitor dependent gastroesophageal reflux disease].

Objective: To investigate the effect of a novel laparoscopic W-H fundoplication in the treatment of proton pump inhibitor (PPI) dependent gastroesophageal reflux disease (GERD). Methods: The clinical data of PPI dependent GERD patients who underwent laparoscopic W-H fundoplication in PLA Rocket Force Characteristic Medical Center from October 1st, 2018 to April 30th, 2019 were analyzed retrospectively. The GERD symptom score, subjective symptom relief, PPI withdrawal, efficacy satisfaction and postoperative complications were followed up and analyzed by a questionnaire. Results: A total of 80 GERD patients were included in this study, and 49 were male and 31 were female, with a median age of 58 years. Among all patients, 85% (68/80) are with esophagitis and 77.5% (62/80) with hiatal hernia. The operation time was 67 (52, 73) minutes, without intraoperative complications and conversion to laparotomy. The postoperative follow-up period was 16 (14, 18) months. The postoperative GERD symptom scores were significantly lower than those before surgery, with an statistical difference (all P<0.05). The subjective remission degree of the overall digestive and respiratory symptoms were 100 (90, 100)% and 100 (80, 100)%, respectively. During the follow-up period, the PPI discontinuation rate was 83% (69/80), and the satisfactory rate was 93% (75/80). Postoperative complications included dysphagia, flatulence, increased exhaust and diarrhea, and the incidence was 61% (49/80), 8% (6/80), 5% (4/80) and 4% (3/80), respectively, and 16% (13/80) of the patients had prolonged occasional mild dysphagia. There was no death, symptomatic recurrence or reoperation. Conclusions: The novel W-H fundoplication has a good medium-term efficacy, with significant GERD symptom control rate and PPI discontinuation rate. The postoperative dysphagia is common, but it is self-limiting and does not affect the satisfaction of the surgical effect.

[Clinical characteristics in patients with hypervirulent Klebsiella pneumoniae infection and its capsular serotypes and multilocus sequence typing].

Objective: To describe the clinical characteristics of hypervirulent Klebsiella pneumoniae (hvKP) infection. To analyze the antibiotic susceptibility of hvKP to provide the empiric antibiotic options. To investigate capsule serotype and sequence type (ST) of hvKP and their correlation with clinical profiles. Methods: hvKP was defined as bacteria isolated from patients with community-acquired pyogenic liver abscess (CA-PLA) with co-infection sites outside liver or a bloodstream infection in a host without underlying biliary tract diseases. Patients with CA-PLA hospitalized in the First Hospital of China Medical University were retrospectively analyzed from January 2011 to December 2017. Antibiotic susceptibility was detected by automatic bacterial identification and antibiotic susceptibility analysis system in vitro. Polymerase chain reaction method and gene sequencing were used to detect the main capsule serotype and ST. Results: A total of 140 cases with hvKP infection were enrolled. The co-infections outside liver abscess included 98 bloodstream infections, 53 pneumonia, 11 perianal abscess, 10 urinary system infections, 3 subphrenic abscess, 3 endophthalmitis, 2 spleen abscess, and other miscellaneous infections including 1 peritonitis, 1 skin and soft tissue infection, 1 myelitis, 1 colitis, 1 psoas major abscess and 1 myocardial abscess. Among the 140 cases, 106 presented with single co-infection site, 32 with 2 sites, and 2 with 3 sites. HvKP manifested high antibiotic susceptibility up to 80% for most commonly used antibiotics. Capsule serotyping of 43 revived isolates indicated that K1 serotype accounted for 53.49% (23/43), K2 34.88 (15/43), K54 2.33% (1/43), K57 2.33% (1/43), and other serotypes 6.98%(3/43). There was no significant distribution among K1, K2, K54 and K57 of hvKP capsule serotypes in patients with or without diabetes mellitus (P>0.05). Multilocus sequence typing (MLST) suggested that ST23 and ST65 were predominant accounting for 39.53% (17/43) and 25.58% (11/43) respectively. No serotype or ST predominance was seen in any of the clinical infections. Conclusion: HvKP is related to a wide spectrum of infectious diseases, including multiple extrahepatic sites and bloodstream infections besides CA-PLA with high antibiotic susceptibility. K1 and K2 are the predominant capsule serotypes, and ST 23 and ST65 are the predominant sequence types.

[Application of dexmedetomidine in radiofrequency ablation of liver tumor].

Objective: To evaluate the efficacy and safety of dexmedetomidine as a basic analgesic sedative for patients with radiofrequency ablation of liver tumors. Methods: A total of 443 liver cancer patients underwent percutaneous radiofrequency ablation in the 302 Hospital of PLA from January 2015 to December 2016 were retrospectively studied. The experimental group was dexmedetomidine group, with a total of 165 cases. The control group was pethidine group with a total of 278 cases. The indexes of systolic blood pressure, diastolic blood pressure, heart rate and respiratory rate of two groups were collected before and after operation, and the VAS score and incidence of nausea and adverse reactions were recorded. Results: The results of the experimental group added dose of pethidine (64.6 mg) lower than that of the control group pethidine dose (90.8 mg), the difference was statistically significant (Z=-10.205 3, P<0.01). The experimental group and the control group with VAS score average value was not statistically significant(Z=1.801 9, P=0.076), group two with 4 points for the critical point of the stratification, more than 4 points and<4 group comparison, the test group VAS score greater than 4 were significantly lower than the control group (χ(2)=7.05, P=0.007 9). The systolic blood pressure and diastolic blood pressure in the experimental group were significantly lower than those before operation (P<0.01), while the systolic blood pressure and diastolic blood pressure in the control group significantly increased compared with those before operation. Dexmedetomidine has the effect of stabilizing hemodynamics. The heart rate of the two groups decreased, and the rate of heart rate decreased in the experimental group. In addition, dexmedetomidine did not significantly increase the incidence of nausea and vomiting compared with the control group. Conclusions: Dexmedetomidine is safe and effective as a basic drug for analgesic and sedative in patients with liver tumor radiofrequency ablation.

[The relationship between acid reflux and esophageal motility, esophagitis and cardiac morphology in gastroesophageal reflux disease].

Objective: To analyze the relationship between the severity of esophageal acid reflux and esophageal motility, esophageal mucosal injury and morphological anatomy of gastroesophageal junction (GEJ) in patients with gastroesophageal reflux disease (GERD). Methods: The clinicaldata of GERD patients who underwent 24 h pH-impedance monitoring, gastroscopy and high-resolution manometry (HRM) from January 2016 to January 2019 in the Gastroesophageal Surgery Department of PLA Rocket Force Characteristic Medical Center were retrospectively analyzed. The patients were divided into non-pathological acid reflux group, mild pathological acid reflux group and moderate to severe pathological acid reflux group according to the DeMeester score. The gender and age of each group were matched, with 60 cases in each group. Statistical analysiswas performed to analyze thedifferences in upper esophageal sphincter pressure, lower esophageal sphincter pressure (LES), LES length, length of ventral LES, percentage of ineffective swallowing, esophagitis, Hill grade of GEJ, and hiatus hernia (HH) in each group. The comparison and correlation analysis are also carried out between the groups. Results: The male-female ratio was 33/27, and the age was (57±13) years in each group. Non-parametric analysis showed that the LES pressure and the length of the ventral LES decreased with the severity of acid reflux, and there was a statistical difference (P= 0.033, P=0.015). The detection rate of HH by HRM increased significantly (χ(2)=0.001) as well. Esophagitis score increased with the severity of acid reflux and there was statistical difference (P<0.001).The detection rate of esophagitis increased significantly (χ(2)<0.001) as well. Hill grading score of GEJ increased with the severity of acid reflux, and there was statistical difference (P<0.001).The detection rate of HH by endoscopy increased significantly (χ(2)<0.001) as well. The correlation between DeMeester score and LES pressure, length of ventral LES, percentage of ineffective swallowing, esophagitis score, and Hill grade score were statistically significant (P<0.05). Conclusions: The esophageal low motility (such as low LES pressure) and anatomical abnormalities (abdominal esophageal shortening, GEJ flabbiness, and even HH formation) of the GEJ regionare significantly associated with the severity of acid reflux. These factors may be important causes of increased acid reflux. In addition, the aggravation of acid reflux can also increase the incidence and severity of esophagitis.

[Investigation and analysis of the status of blood-borne occupational exposure of medical staff in a top three hospital and intervention measures].

Objective: To understand the current situation of blood-borne occupational exposure among health care workers and evaluate the intervention effect of PDCA. Methods: Retrospective survey was adopted to investigate and analyze the blood-borne occupational exposure incidents in a hospital from January 2015 to December 2018, and to compare the intervention effects after PDCA management. Results: A total of 82 cases of occupational exposure occurred from 2015 to 2017, and only 9 cases happened after the implementation of PDCA intervention. The exposed population was mainly consisted of nurses (59 cases, 64.83%) , and mainly with low-working age (1-5 years) (56 cases, 61.54%) , and the main source of exposure was hepatitis B (34 cases, 37.36%) . In addition, after the implementation of PDCA, the vaccination rate of personnel was 77.78%, the standardized field treatment rate was 100%, the preventive drug use rate was 88.89%; The qualified rate of occupational protection assessment was higher than that before intervention, which all shows the difference was statistically significant (P<0.05) . Conclusion: With the guide of PDCA management, Strengthen the training of new employees or ones with low working years as well as their awareness of protection, and standardize the relevant operational procedures, which can significantly improve the prevention of blood-borne occupational exposure and stress management of medical staff.

Tannerella forsythia and coating color on the tongue dorsum, and fatty food liking associate with fat accumulation and insulin resistance in adult catch-up fat.

BACKGROUND/OBJECTIVES: We aimed to determine the alteration of Tannerella forsythia and coating color on the dorsal tongue, and fatty food liking in catch-up fat in adult (CUFA), as well as the probable associations between fat accumulation, insulin resistance (IR) and these changes. SUBJECTS/METHODS: T. forsythia on the tongue dorsum, fatty food liking, fat accumulation and insulin sensitivity were investigated in CUFA humans and rats, and tongue-coating color was observed in CUFA individuals. We further determined the changes of fatty food liking, fat accumulation and IR in T. forsythia-infected rodents by oral lavage. RESULTS: Increases in fat accumulation, IR, percentage of subjects with yellow tongue coating and that with T. forsythia detected were observed in CUFA individuals. Additionally, the fat ranking scores were significantly lower and the hedonic ratings of low-fat options of sampled food were lower, while the ratings of high-fat options were remarkably higher in CUFA subjects. Additionally, T. forsythia level elevated in CUFA rats, and fatty food liking, fat accumulation and IR increased in CUFA and T. forsythia-infected animals, with the increases in T. forsythia infection and fatty food liking preceding the occurrence of fat accumulation and IR. CONCLUSIONS: T. forsythia and yellow coating on the dorsal tongue and fatty food liking associate fat accumulation and IR in CUFA. Moreover, we tentatively put forward that T. forsythia, which is very important in yellow tongue-coating microbiota, and its consequent increases in fatty food liking, might be crucial in the development of fat accumulation and IR in CUFA.