Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

AIM: To evaluate the applicability of Chinese dry eye questionnaire in college students using the ocular surface disease index(OSDI)questionnaire as a reference.METHODS: Cross-sectional study. A total of 711 college students from Nanyang Medical College were enrolled in the study and assessed for dry eye condition using OSDI questionnaire and Chinese dry eye questionnaire. The response rate of each question in the two questionnaires was counted. Cronbach α was calculated to evaluate the internal consistency of both questionnaires. Correlation between the total scores of the two questionnaires was analyzed to evaluate the criterion validity. Based on OSDI scores, the discriminant validity of Chinese dry eye questionnaire was evaluated; receiver operating characteristic(ROC)curves was plotted for Chinese dry eye questionnaire scores, area under the ROC curve(AUC)was calculated, and diagnostic thresholds and corresponding sensitivity and specificity were also analyzed.RESULT: The response rates of the 12 questions on the OSDI questionnaire were 33.2%-100.0%, while it was 100.0% for each question on the Chinese dry eye questionnaire. The Cronbach α values of OSDI questionnaire and Chinese dry eye questionnaire were 0.905 and 0.789, respectively. The Chinese dry eye questionnaire score was positively correlated with the OSDI score(rs=0.712, P<0.001). According to OSDI questionnaire scores, dry eye severity was divided into normal group, mild dry eye group, moderate dry eye group and severe dry eye group. The scores of Chinese dry eye questionnaire in these groups were 4.00(2.00, 6.00), 9.00(7.00, 11.00), 12.00(9.00, 14.00)and 16.00(13.50, 22.00), respectively, which increased with the severity of dry eye, and the overall difference was statistically significant(P<0.001), as well as pairwise comparison between groups(P<0.05). The AUCs of Chinese dry eye questionnaire in distinguishing normal population from dry eye population, mild dry eye from moderate dry eye, moderate dry eye from severe dry eye were 0.862, 0.661 and 0.769, respectively, and the diagnostic thresholds were 6.5, 11.5 and 14.5, respectively.CONCLUSION:Chinese dry eye questionnaire has an equivalent reliability, validity, discriminant ability and better response rate for dry eye screening and epidemiological survey among college students in China compared with OSDI questionnaire.

OBJECTIVE: Flavonoids are the bioactive compounds in safflower (Carthamus tinctorius), in which chalcone synthase (CHS) is the first limiting enzyme. However, it is unclear that which chalcone synthase genes (CHSs) are participated in flavonoids biosynthesis in C. tinctorius. In this study, the CHSs in the molecular characterization and enzyme activities were investigated. METHODS: Putative chalcone biosynthase genes were screened by the full-length transcriptome sequences data in C. tinctorius. Chalcone biosynthase genes in C. tinctorius (CtCHSs) were cloned from cDNA of flowers of C. tinctorius. The cloned gene sequences were analyzed by bioinformatics, and their expression patterns were analyzed by real-time PCR (RT-PCR). The protein of CtCHS in the development of flowers was detected by polyclonal antibody Western blot. A recombinant vector of CtCHS was constructed. The CtCHS recombinant protein was induced and purified to detect the enzyme reaction (catalyzing the reaction of p-coumaryl-CoA and malonyl-CoA to produce naringin chalcone). The reaction product was detected by HPLC and LC-MS. RESULTS: Two full-length CtCHS genes were successfully cloned from the flowers of safflower (CtCHS1 and CtCHS3), with gene lengths of 1525 bp and 1358 bp, respectively. RT-PCR analysis showed that both genes were highly expressed in the flowers, but the expression of CtCHS1 was higher than that of CtCHS3 at each developmental stage of the flowers. WB analysis showed that only CtCHS1 protein could be detected at each developmental stage of the flowers. HPLC and LC-MS analyses showed that CtCHS1 could catalyze the conversion of p-coumaryl-CoA and malonyl-CoA substrates to naringin chalcone. CONCLUSION CtCHS1 is involved in the biosynthesis of naringin chalcone in safflower.

Humans ; Esophageal Achalasia/genetics* ; Cardia ; Nerve Tissue Proteins ; Nuclear Pore Complex Proteins

Objective: To explore the feasibility and safety of the gasless transoral vestibular robotic thyroidectomy using skin suspension. Methods: The clinical data of 20 patients underwent gasless transoral vestibular robotic thyroidectomy in the Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from February 2022 to May 2022 were retrospectively analyzed. Among them, 18 were females and 2 were males, aged (38.7±8.0) years old. The intraoperative blood loss, operation time, postoperative hospital stay, postoperative drainage volume, postoperative pain visual analogue scale (VAS) score, postoperative swallowing function swallowing impairment score-6 (SIS-6), postoperative aesthetic VAS score, postoperative voice handicap index-10 (VHI-10) voice quality, postoperative pathology and complications were recorded. SPSS 25.0 was used for statistical analysis of the data. Results: The operations were successfully completed without conversion to open surgery in all patients. Pathological examination showed papillary thyroid carcinoma in 18 cases, retrosternal nodular goiter in 1 case, and cystic change in goiter in 1 case. The operative time for thyroid cancer was 161.50 (152.75, 182.50) min [M (P₂₅, P₇₅), the same below] and the average operative time for benign thyroid diseases was 166.50 minutes. The intraoperative blood loss 25.00 (21.25, 30.00) ml. In 18 cases of thyroid cancer, the mean diameter of the tumors was (7.22±2.02) mm, and lymph nodes (6.56±2.14) were dissected in the central region, with a lymph node metastasis rate of 61.11%. The postoperative pain VAS score was 3.00 (2.25, 4.00) points at 24 hours, the mean postoperative drainage volume was (118.35±24.32) ml, the postoperative hospital stay was 3.00 (3.00, 3.75) days, the postoperative SIS-6 score was (4.90±1.58) points at 3 months, and the postoperative VHI-10 score was 7.50 (2.00, 11.00) points at 3 months. Seven patients had mild mandibular numbness, 10 patients had mild cervical numbness, and 3 patients had temporary hypothyroidism three months after surgery and 1 patient had skin flap burn, but recovered one month after surgery. All patients were satisfied with the postoperative aesthetic effects, and the postoperative aesthetic VAS score was 10.00 (10.00, 10.00). Conclusion: Gasless transoral vestibular robotic thyroidectomy using skin suspension is a safe and feasible option with good postoperative aesthetic effect, which can provide a new treatment option for some selected patients with thyroid tumors.
Male ; Female ; Humans ; Adult ; Middle Aged ; Thyroidectomy/adverse effects* ; Robotic Surgical Procedures/adverse effects* ; Retrospective Studies ; Blood Loss, Surgical ; Hypesthesia/surgery* ; Neck Dissection/adverse effects* ; Thyroid Neoplasms/surgery* ; Pain, Postoperative/surgery* ; Postoperative Complications/etiology*

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.
Male ; Rats ; Animals ; Reserpine ; Dopamine ; Rats, Wistar ; Hypotension/chemically induced* ; Norepinephrine

Child ; Humans ; Inflammatory Bowel Diseases ; Organic Anion Transporters/genetics*

Objective: To analyze the clinical features, treatment and prognosis of solitary rectal ulcer syndrome (SRUS) in children. Methods: The clinical data of 7 children who were diagnosed with SRUS in Department of Gastroenterology in Guangzhou Women and Children' Medical Center from January 2019 to December 2021 were retrospectively analyzed. The clinical data including general demographics, clinical presentations, endoscopic and histologic features, treatment and outcome were extracted from hospital medical records. Results: The 7 patients were all males, and the age of onset was 6-12 years. The course before diagnosis was 2-36 months. The most common symptom was rectal bleeding (6 cases) and most common findings at initial colonoscopy were ulcer in 3 cases and protuberance in 4 cases, both located only in rectum. The intestinal histopathology of 5 cases showed characteristic fibromuscular obliteration of lamina propria. Five children were treated with mesalamine granules or suppositories, and 2 cases underwent local excision. The follow-up lasted for 5-24 months and found symptoms relieved in 5 cases, improved in 1 case, and no remission in 1 case. Colonoscopy after the treatment was performed in 5 children, among whom 2 cases achieved mucosal healing. Conclusions: SRUS in children is mainly presented with rectal bleeding, and has characteristic histological change of ulcer and protuberance in endoscopy. Pathology is crucial for diagnosis and differential diagnosis. Both the medical and surgical treatment are effective for SRUS.
Child ; Colonoscopy ; Female ; Gastrointestinal Hemorrhage/therapy* ; Humans ; Male ; Rectal Diseases/therapy* ; Rectum/surgery* ; Retrospective Studies ; Ulcer/therapy*

Objective: This study aims to survey the incidence of surgical site infection (SSI) in China and to analyze its risk factors, so as to prevent and control SSI after colorectal surgery. Methods: An observative study was conducted. Based on a program of Chinese SSI Surveillance from 2018 to 2020, the clinical data of all adult patients undergoing colorectal surgery during this time period were extracted. These included demographic characteristics and perioperative clinical parameters. Minors, pregnant women, obstetric or gynecological surgery, urological system surgery, retroperitoneal surgery, resection of superficial soft tissue masses, and mesh or other implants were excluded. A total of 2122 patients undergoing colorectal surgery from 50 hospitals were included, including 1252 males and 870 females. The median age was 63 (16) years and the median BMI was 23 (4.58) kg/m². The primary outcome was the incidence of SSI within 30 days after colorectal surgery. The secondary outcomes were mortality within 30 days postoperatively, length of ICU stays and postoperative hospital stays, and cost of hospitalization. Patients were divided into the SSI group and non-SSI group based on the occurrence of SSI. Multivariable logistic regression was performed to analyze risk factors of SSI after colorectal surgery, and subgroup analysis was conducted for open and laparoscopic surgery. Results: The incidence of SSI after colorectal surgery was 5.6% (119/2122), including 47 cases (47/119, 39.5%) with superficial incisional infections, 24 cases (24/119, 20.2%) with deep incisional infections, and 48 cases (48/119, 40.3%) with organ/space infections. The occurrence of SSI significantly increased mortality [2.5% (3/119) vs. 0.1%(3/2003), χ²=22.400, P=0.003], the length of ICU stay [0 (1) day vs. 0(0) day, U=131 339, P<0.001], postoperative hospital stay [18.5 (12.8) days vs. 9.0 (6.0) days, U=167 902, P<0.001], and medical expenses [75 000 (49 000) yuan vs. 60 000 (31 000) yuan, U=126 189, P<0.001] (P<0.05). Multivariate analysis revealed that hypertension (OR=1.782, 95%CI: 1.173-2.709, P=0.007), preoperative albumin level (OR=1.680, 95%CI: 1.089-2.592, P=0.019), a contaminated or infected incision (OR= 1.993, 95%CI: 1.076-3.689, P=0.028), emergency surgery (OR=2.067, 95%CI: 1.076-3.972, P=0.029), open surgery (OR=2.132, 95%CI: 1.396-3.255, P<0.001), and surgical duration (OR=1.804, 95%CI: 1.188-2.740, P=0.006) were risk factors for SSI, while preoperative skin preparation (OR=0.478, 95%CI: 0.310-0.737, P=0.001) was a protective factor for SSI. Subgroup analysis was performed on patients undergoing open or laparoscopic surgery. The incidence of SSI in the open surgery group was 10.2%, which was significantly higher than that in the laparoscopic or robotic group (3.5%, χ²=39.816, P<0.001). Subgroup analysis identified that a contaminated or infected incision (OR=2.168, 95%CI: 1.042-4.510, P=0.038) and surgical duration (OR=2.072, 95%CI: 1.171-3.664, P=0.012) were risk factors for SSI after open surgery, while mechanical bowel preparation (OR=0.428, 95%CI: 0.227-0.807, P=0.009) and preoperative skin preparation (OR=0.356, 95%CI: 0.199-0.634, P<0.001) were protective factors for SSI after open surgery. In laparoscopic surgery, diabetes mellitus (OR= 2.292, 95%CI: 1.138-4.617, P=0.020) and hypertension (OR=2.265, 95%CI: 1.234-4.159, P=0.008) were risk factors for SSI. Conclusions: The incidence of SSI after colorectal surgery is 5.6%. Minimally invasive surgery should be selected to reduce the occurrence of postoperative SSI. To prevent the occurrence of SSI after open surgery, skin preparation and mechanical bowel preparation should be performed before the operation, and the duration of the operation should be shortened as much as possible. In the perioperative period, care of patients with hypertension, diabetes, and contaminated or infected incisions should be given particular attention.
Adult ; Albumins ; China/epidemiology* ; Colorectal Surgery/adverse effects* ; Female ; Humans ; Hypertension/complications* ; Male ; Middle Aged ; Pregnancy ; Surgical Wound Infection/etiology*