ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective:To investigate the role of m.4435A>G and YARS2 c.572G>T(p.G191V)mutations in the development of essential hypertension.Methods:A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data.Clinical data were collected,and a molecular genetic study was conducted in the proband and his family members.Peripheral venous blood was collected,and immortalized lymphocyte lines constructed.The mitochondrial transfer RNA(tRNA),mitochondrial protein,adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),and reactive oxygen species(ROS)in the constructed lymphocyte cell lines were measured.Results:Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation.The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability,which may influence the anticodon ring structure.Compared with the control group,the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis,mitochondrial protein expression,ATP production and MMP levels,as well as increased ROS levels(all P<0.05).Conclusion:The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction,indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.

OBJECTIVE To analyze the narrow-band imaging(NBI)endoscopic characteristics of recurrent early glottic carcinoma patients after undergoing CO2 laser surgery with a suspend laryngoscopy.METHODS A retrospective study was conducted on patients with early-stage glottic carcinoma(Ⅰ-Ⅱ stage)who received CO2 laser surgery under supportive laryngoscopy at the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2017 to December 2023.The medical history,treatment methods,laryngoscopy(including common white light endoscopy and NBI endoscopy),imaging examinations,and pathological results of patients with recurrent glottic carcinoma were collected at different time points including preoperation,postoperative 1 month,postoperative 3 months,and postoperative 6 months.The endoscopic characteristics of NBI in patients with recurrent glottic carcinoma were summarized.RESULTS First,among 18 patients with early-stage glottic cancer recurrence after CO2 laser,the diagnostic rate of NBI endoscopy for laryngeal cancer recurrence(88.89％,16/18)was significantly higher than that of common white light endoscopy(55.56％,10/18)(χ2=4.985,P=0.026).The intraepithelial papillary capillary loop(IPCL)was classified as a vertical vessel according to ELS in all relapsed patients.However,according to Ni classification,the IPCL of the 72.22％(13/18)were classified as type V,while the IPCL of 27.78％(5/18)showed suspicious abnormal neovascularization(punctate or dilated and curved).The proportion of patients with abnormal IPCL on the surgical surface at 1 month,3 months,and 6 months postoperatively was 0.00％,27.78％(5/18),and 61.11％(11/18),respectively,with statistically significant differences(χ2=16.164,P<0.001),which indicated that the longer the follow-up time for recurrent laryngeal cancer patients,the higher the proportion of patients with abnormal IPCL on the surface of the surgical area under NBI endoscopy.CONCLUSION For early glottic carcinoma after CO2 laser surgery with a suspend laryngoscopy,the appearance of suspicious new blood vessels with type Ⅴ IPCL and punctate or dilated curvature under NBI endoscopy may indicate early recurrence of laryngeal cancer.

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method for determination of tobramycin in human serum,and examine the utility of the method in a clinical pharmacokinetic study of tobramycin inhalation.Methods Serum samples were pretreated by solid phase extraction with tobramycin-D12 as internal standard.Chromatographic separation was performed on a TitankHilic(2.1 mm × 100 mm,3 μm)column.The mobile phase consisted of0.1％formic acid-acetonitrile and 0.1％formic acid aqueous solution at a flow rate of 0.4 mL/min.Electrospray ionization source and multiple reaction monitoring(MRM)scanning were used for monitoring the quantitative ion pairs with m/z 468.3→m/z 163.3(tobramycin)and m/z 480.6→m/z 166.2(tobramycin-D12).The established method was investigated in terms of selectivity,interaction,concomitant medication,standard curve and lower limit of quantitation,precision and accuracy,recovery,matrix effect,and stability of tobramycinin.Results The linear range of tobramycin was 0.050 0-10.0 mg/L(R2=0.999 5).The intra-and inter-batch precision was satisfactory(coefficient of variation[CV]≤3.6％).The accuracy ranged from-0.4％to 6.0％.The matrix effect factor(MF)in human serum samples(including hemolysis and lipemia)ranged from 92.2％to 94.9％(CV≤2.7％).The recovery of tobramycinin was 79.5％-81.9％in serum samples,while the recovery of internal standard was 78.9％.The analyte was stable in serum samples for 72 h at room temperature and for 274 days at-20℃/-70℃.The pharmacokinetic study of tobramycin inhalation in bronchiectasis patients showed that after continuous administration of tobramycin 300 mg twice a day to 3 patients,the mean Cmax of tobramycin was(0.72±0.61)mg/L on Day 1 and(0.76±0.73)mg/L on Day 28,respectively.The corresponding Tmax was(1.83±0.61)h and(1.50±0.50)h,respectively.Conclusions The UPLC-MS/MS method established in this study is sensitive,accurate and rapid.It is successfully applied to the clinical pharmacokinetic study of tobramycin inhalation.The method may be suitable for therapeutic drug monitoring of tobramycin in clinical practice.

Objective To explore the effect of intermittent fasting combined with diversified management mode on weight loss of overweight and obese people. Methods A total of 120 overweight and obese patients were selected as research objects, and randomly divided into control group (n=60) and experimental group (n=60). The control group was given intermittent fasting, and the experimental group was given diversified management mode on the basis of the control group. Waist circumference, body mass, body mass index (BMI), waist-to-hip ratio and blood lipid level were compared between the two groups; the scores of hunger, satiety, satisfaction and the incidence of adverse reactions were compared between the two groups. Results After intervention, waist circumference, body mass, BMI, waist-to-hip ratio, total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the experimental group were significantly lower, and high-density lipoprotein cholesterol (HDL-C) was significantly higher than that in the control group (P < 0.05). After intervention, the hunger score of the experimental group was significantly lower, and the satiety score and satisfaction score were significantly higher than those of the control group (P < 0.05). The total incidence of adverse reactions in the experimental group was 6.67%, which was significantly lower than 20.00% in the control group (P < 0.05). Conclusion The application of intermittent fasting combined with diversified management mode in overweight and obese people is better, which can improve the relevant clinical indicators and blood lipid levels, and has high safety.

Objective:To construct a new reporter mycobacteriophage, ΦFN, based on a nanoluciferase (Nluc) reporter system, and to analyze its ability to detect drug resistance in Mycobacterium tuberculosis ( Mtb). Methods:A Nluc reporter system controlled by P furAma promoter was constructed and integrated into Mycobacterium smegmatis ( Msm) genome to assess its reporting ability in mycobacteria. Then the P furAma- nluc reporter system was integrated into TM4 mycobacteriophage genome to construct a new phage termed ΦFN. A rapid procedure for detecting drug resistance in mycobacteria using ΦFN was established by adjusting conditions such as drug exposure time and time of infection. The susceptibility of 52 clinical isolates of Mtb with known drug resistance to three first-line anti-tuberculosis drugs were tested in 96-well plates. Results:The recombinant Msm mc 2155 expressing P furAma- nluc repoerter system could generate luminescence signal at a low limit of 100 colony-forming unit (CFU), which was lower than the previously reported nluc system controlled by Pleft promoter. The detection limit of ΦFN for mycobacteria reached 100 CFU within 24 h by luminescent microplate reader. After 48 h of antibiotic exposure and 24 h of phage incubation, no luminescence signal could be detected when susceptible strains were below 10 5 CFU, which could effectively distinguish susceptible strains and rapidly detect drug resistance. The drug susceptibility of 52 clinical isolates of Mtb to rifampin, isoniazid and streptomycin was tested using ΦFN, and the accuracy was 51/52, 48/52 and 49/52, respectively, by using the conventional drug susceptibility test, Lwenstein-Jensen culture medium assay, as reference. Conclusions:The new recombinant luminescent reporter phage, ΦFN, showed high accuracy in detecting the drug susceptibility of Mtb to rifampicin, isoniazid and streptomycin and it only took three days. It is expected to be a new simple assay for the rapid detection of drug susceptibility of Mtb.

Pheochromocytoma/paraganglioma is an adrenal tumor that secrets catecholamines and is extremely rare in pregnant women. Its clinical presentation is lack of specificity, and the combination of low prevalence and nonspecific clinical presentation makes diagnosis and treatment difficult. In this study, the clinical data and prognosis of 5 pregnant patients with pheochromocytoma/paraganglioma were analyzed. It was found that hypertension first occurred in 4 patients during pregnancy, and the clinical manifestations of each case were different. Surgical treatment is the first choice in the treatment, patients who cannot operate can choose radionuclide therapy, chemotherapy and targeted therapy. Through follow-up, they all showed recurrence and metastasis at different times. Among them, the patients who continued to be pregnant to the middle and late stages of surgical treatment progressed rapidly, and there were multiple bone metastases throughout the body in a short period of time, and two cases died in a short period of time. Therefore, effective diagnosis, individualized treatment and lifelong follow-up are particularly important.

Objective:To explore the treatment experience of holmium laser enucleation of prostate (HoLEP) with preservation of longitudinal urethral mucosa at 12 o’clock for benign prostatic hyperplasia (BPH) with small-medium gland.Method:From October 2018 to April 2021, 256 patients diagnosed BPH with small-medium gland(prostate volume 30-60 ml)were retrospectively analyzed, including general information, way of operation, intraoperative parameters and follow-up data. From October 2018 to June 2020, 186 BPH patients underwent conventional HoLEP, which did not retain longitudinal urethral mucosa at 12 o’clock as a conventional operation group. From July 2020 to April 2021, 70 BPH patients underwent modified HoLEP, which retained longitudinal urethral mucosa at 12 o’clock as a modified operation group. There was no significant difference between the two groups( P>0.05) in term of the age[(70.5±4.4)years old vs.(68.5±3.2)years old], Q max[(7.5±2.8)ml/s vs.(7.5±2.1)ml/s], IPSS[(20.3±4.6)vs.(21.4±3.7)], QOL[(4.5±1.0)vs.(4.2±1.4)], postvoid residual volume[(126.9±29.36)ml vs.(132.2±32.3)ml], PSA[(1.5±1.3)ng/ml vs.(1.8±1.1)ng/ml] and prostate volume[(48.1±11.1)ml vs.(48.0±12.7)ml]. Both groups were treated with "trefoil" enucleation of prostate. The modified group was improved compared with the conventional group by retaining a 12 o’clock longitudinal urethra mucosa from the bladder neck to the apex of the prostate. The technical improvements were as follows: ①the left lobe of prostate was removed from at 5 o’clock at the verumontanum to 1 o’clock at the prostate apex along the gap between the hyperplasia gland and the surgical envelope; ②the right lobe was removed from 7 o’clock at the verumontanum to 11 o’clock at the apex; ③the urethra mucous membrane was cut vertically from 1 and 11 o’clock at the bladder neck to 1 and 11 o’clock at the apex respectively, and retaining the longitudinal mucous membrane between 11 and 1 o’clock (including 12 o’clock). Efficacy and postoperative complications of the two groups were compared. Results:The difference between the conventional group and the modified group in operation time[(36.5±10.4)min vs.(40.7±9.7)min], enucleated glandular weight[(35.5±12.2)g vs.(31.6±10.4)g], hemoglobin decline[(6.1±2.2)g/L vs.(5.6±2.5) g/L], postoperative hospitalization time [(1.2±0.2)d vs.(1.5±0.4)d]and catheter indwelling duration[(2.3±1.3)d vs.(2.0±1.0)d] were not statistically significant ( P>0.05). There were 252 patients for follow-up, including 183 cases in the conventional group and 69 cases in the modified group, and 4 cases were lost to follow-up. Mean time of follow-up was 8.4 months. In both groups, postoperative IPSS were 5.4±2.3 and 5.9±1.2 respectively, QOL1.5±0.3 and 2.0±1.0 respectively, Q max(24.3±9.2)ml/s and (22.5±11.3)ml/s respectively and postvoid residual volume (8.3±4.5)ml and (7.7±2.9)ml respectively, which were significantly different from that before the operation ( P<0.05). However, there was not significant difference between the two groups ( P>0.05). The postoperative immediate urinary continence rate of the conventional group and modified group were 85.2% (156/183), 98.6% (68/69), respectively, and two groups had statistical differences ( P<0.05). Incidence of postoperative bladder neck contraction were 4.4% (8/183) and 0 respectively in the conventional and modified group, whose difference was significant( P<0.05). Conclusions:HoLEP with preservation of longitudinal urethral mucosa at 12 o'clock is the same effective as conventional operation in the treatment of BPH with small-medium gland, likewise it could significantly improve immediate urinary continence rate and reduce the incidence of bladder neck contraction.

We retrospectively analyzed the clinical data of 21 patients diagnosed with BPH combined with mild urethra stenosis from January 2018 to December 2020. 12 patients underwent holmium laser enucleation of prostate (HoLEP). There were 3 cases of serious urethra stenosis requiring repeat surgical treatment after surgery, 9 cases of unobstructed voiding, 4 cases of reverse ejaculation and 2 cases of temporary urinary incontinence. 9 patients underwent laparoscopic simple prostatectomy (LSP) and all patients had unobstructed voiding. There were no cases of severe urethral stricture, temporary urinary incontinence and retrograde ejaculation in LSP group. LSP has reduced the risk of a repeat urethral surgery because of transurethral operation increasing the degree of urethra stenosis.

Objective To investigate the risk factors for myocardial injury after Nano-Knife surgery in patients with pancreatic cancer, and to establish a nomogram model for risk prediction. Methods A retrospective analysis was performed for the clinical data of 92 patients with pancreatic cancer who underwent Nano-Knife surgery in The Fifth Affiliated Hospital of Zhengzhou University from September 2020 to November 2021, with serum cardiac troponin I > 0.03 ng/mL within 3 days after surgery as the diagnostic criteria for myocardial injury, the patients were divided into myocardial injury group with 51 patients and non-myocardial injury group with 41 patients. Related baseline data were collected for all patients, including age, sex, body mass index, American Society of Anesthesiologists classification, smoking history, alcohol abuse history, and preoperative comorbidities. The Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Univariate and multivariate logistic regression analyses were used to screen out the variables with statistical significance, and the factors screened out were used to establish a nomogram for predicting the risk of myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the discriminatory ability and clinical utility of the model. Results Compared with the non-myocardial injury group, the myocardial injury group had a significantly longer ablation time ( χ 2 =7.410, P =0.006), a significantly greater number of probes ( χ 2 =6.130, P =0.047), and a significantly higher proportion of patients with preoperative hypertension ( χ 2 =12.124, P < 0.001) or chronic kidney disease ( χ 2 =12.829, P < 0.001). The univariate logistic regression analysis showed that tumor diameter, ablation time, surgical procedure, number of probes, history of hypertension, and history of chronic kidney disease were associated with the development of myocardial injury (all P < 0.05), and the multivariate logistic regression analysis showed that tumor diameter (odds ratio [ OR ]= 3.94, 95% confidence interval [ CI ]: 1.09-14.18, P =0.036), ablation time ( OR =4.15, 95% CI : 1.30-13.27, P =0.016), surgical procedure ( OR =6.92, 95% CI : 1.92-25.07, P =0.003), and history of hypertension ( OR =4.07, 95%CI: 1.12-14.77, P =0.034) were independent risk factors for myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. An AUC of 0.859 showed that the nomogram had good discriminatory ability and clinical utility. Conclusion There is a relatively high incidence rate of myocardial injury after Nano-Knife surgery in patients with pancreatic cancer. Preoperative hypertension, tumor diameter > 4 cm, and ablation time > 1 hour are independent risk factors for myocardial injury, and the surgical procedure of Nano-Knife surgery and bypass anastomosis can increase the risk of myocardial injury. The nomogram has a good effect in predicting the risk of myocardial injury.