Objective To establish a highly sensitive,stable,and universally applicable ultra-high-performance liquid mass spectrometry tandem method(UPLC-MS/MS)for simultaneous determination of nirmatrelvir and ritonavir blood concentrations in human plasma.Methods The separation was performed on an ACQUITY UPLC BEH C18 column(2.1 mm× 50 mm,1.7 μm)with gradient elution,and the mobile phase consisted of 0.1％formic acid-water and 100％acetonitrile at the flow rate of 0.3 mL·min-1.The column temperature was 45℃,and the injection volume was 2 μL.Electrospray ionization as ion source(ESI+)was used as the ion source and multiple reactions monitoring mode(nirmatrelvir m/z 500.20→319.10,nirmatrelvir-D9 m/z 508.59→328.10,ritonavir m/z 721.30→426.10,13C,2H3-ritonavir m/z 725.30→426.10)was adopted.Thirty patients with coronavirus disease 2019(COVID-19)treated with nirmatrelvir and ritonavir at the People's Hospital of Changxing County in Jan.2023 were selected to measure their steady-state trough concentrations of nirmatrelvir and ritonavir after 3 days of treatment.Results The linear range of nirmatrelvir was 0.100-10.0 μg·mL-1(R2=0.997 2),and the linear range of nirmatrelvir was 0.050-5.00 μg·mL-1(R2=0.995 2).The recovery rates of nirmatrelvir and lopinavir were both＞90％and the intra-batch and inter-batch precision relative standard deviations(RSDs)were both＜10％.Additionally,the recovery ranges for nirmatrelvir and lopinavir were 91.5％-97.0％,and the matrix effects ranged from 92.4％to 97.7％.The results of clinical samples showed that the plasma concentrations of nirmatrelvir and ritonavir in patients with COVID-19 varied greatly among individuals.Conclusion The method for simultaneous determination of nirmatrelvir and ritonavir concentrations in human plasma established in this study is convenient,highly specific,highly accurate,with high precision,which is suitable for monitoring the concentrations of nirmatrelvir and ritonavir in patients.

OBJECTIVE To test and compare the median effective dose(ED50) of ciprofol for gastroscope in patients of different genders and ages. METHODS Patients who planed to undergo gastroscope examination and treatment from March 2023 to April 2023 were selected, and divided into four groups according to stratified random method: N1 group(non-elderly male patients), N2 group(non-elderly female patients), N3 group(elderly male patients), and N4 group(elderly female patients). All patients received intravenous injection of 0.1 μg·kg−1 sufentanil followed by injection of the test dose of ciprofol according to Dixon’s modified sequential method. Gastroscope was performed after the disappearance of the eyelash reflex. The initial dose of ciprofol in all four groups was 0.4 mg·kg−1, and the ratio of adjacent doses was 1∶1.1. The next patient would receive a 10% increase in the dose of ciprofol if the patient experienced positive reactions such as coughing, frowning, and body movements during the endoscopy process. Otherwise, it would be judged as a negative reaction, and the next patient would receive a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points. The Probit regression analysis method was used to calculate the ED50 of ciprofol for four groups. RESULTS The ED50 of ciprofol combined with 0.1 μg·kg−1 sufentanil for gastroscope in the non-elderly men, non-elderly women, elderly men, and elderly women were 0.409, 0.373, 0.356, 0.327 mg·kg−1, respectively. The ED50 of ciprofol in the N1 group was significantly higher compared with the N2 group and N3 group(P<0.05). The ED50 of ciprofol in the N4 group was significantly lower compared with the N2 group and N3 group(P<0.05). CONCLUSION The ED50 of ciprofol is significantly different among gastroscope patients of different genders and ages, which is lower in female patients than in male patients, and is lower in older patients than in non-elderly patients.

Objective:To perform two-step clustering analysis based on urodynamics in patients with neurogenic bladder (NB) and exploring characteristics affecting success rate of sacral neuromodulation (SNM).Methods:The data of 174 NB patients who received SNM therapy in our hospital from September 2018 to August 2023, were retrospectively analysed. There were 94 males and 80 females, with average age of (50.4±17.9)years, median duration of 2 (1, 3)years, and body mass index of 21.5 (20, 25) kg/m 2. Among them, 50 patients had chronic diseases (hypertension or diabetes). Additionally, 77 patients (44.3%) presented with voiding symptoms, 47 patients (27.0%) with storage symptoms, and 50 patients (28.7%) with mixed symptoms. The etiologies included spinal cord lesions in 110 patients (63.2%), brain lesions in 21 patients (12.1%), peripheral nerve lesions in 36 patients (20.7%), and other causes in 7 patients (4.0%). All patients underwent urodynamics and SNM phase 1 test. If patient's subjective symptoms or objective indicators improved > 50%, it is defined as treatment success and feasible to received second stage of SNM. The success rate was analyzed. Clinical indicators and urodynamic parameter were collected for exploring the difference of the above indicators between two groups (with or without conversion). The 174 patients were grouped using two-step clustering analysis, dividing them into two groups. The differences in clinical data, urodynamic parameters, and the conversion rate of SNM phase II between the two groups were compared. Results:Among these patients, 126 (72%) underwent the second stage of SNM. Compared with the non-conversion group, patients in the conversion group exhibited the following characteristics: high proportion of female[51.6% (65/126) vs. 31.2% (15/48)], younger[(48.1± 18.3)year vs. (56.4±15.4) year], lower proportion of history of chronic disease[23.9% (30/126) vs. 41.7% (20/48)], storage predominant symptoms predominant[33.3% (42/126) vs. 10.4% (5/48)], sensitive bladder sensation[50.0% (63/126) vs. 11.1% (14/48)], normal detrusor contractility [26.2% (33/126) vs. 10.4% (5/48)] and detrusor-sphincter dyssynergia [21.4% (27/126) vs. 4.2% (2/48)]and lower post-void residual [105.5(49.3, 231.3) ml vs. 197.9(114.8, 284.8) ml], ( P<0.05). After excluding multicollinearity, patients were divided into two group mainly based on coordination, detrusor stability, and detrusor contractility through two-step clustering analysis: 98 patients in Group 1 and 76 patients in Group 2. The success rate was higher in Group 2 [82.9% (63/76) vs. 64.3% (63/98), P=0.006]. Compared with Group 1, Group 2 exhibited the following characteristics: higher proportion of storage symptoms [43.4% (33/76) vs. 14.3% (14/98)], sensitive bladder sensation [67.1% (51/76) vs. 26.5% (26/98)], detrusor overactivity [46.1% (35/76) vs. 3.1% (3/98)], normal detrusor contractility [43.4% (33/76) vs. 5.1% (5/98)], and detrusor-sphincter dyssynergia [38.2% (29/76) vs. 0] ( P all<0.05). Additionally, group 2 had lower post-void residual [69.0 (23.8, 136.6) ml and 197.9 (123.2, 287.4) ml] and smaller bladder capacity [(281.9±144.9) ml vs. (430.4±176.7) ml] ( P all<0.01). Conclusions:Patients with storage symptoms, low post-void residual, sensitive bladder sensation, detrusor overactivity, normal contractility, or detrusor-sphincter dyssynergia indicate a higher conversion rate to second stage, making them more suitable for SNM testing.

Objective:To investigate the diagnostic value of prenatal MRI in the detection of abnormal placental cord insertions (APCIs) comparing with prenatal ultrasound and pathological examination.Methods:A retrospective data collection was conducted on 440 patients who underwent both prenatal placental ultrasound and MRI at the Foshan Women and Children Hospital from December 2013 to December 2021. Among them, 37 cases were APCIs confirmed by surgery or pathology. The prenatal placental MRI findings were analyzed and compared with prenatal ultrasound diagnosis. The diagnostic efficacy of prenatal MRI and ultrasound in diagnosing APCIs was calculated.Results:Among the 37 cases of APCIs confirmed by surgery or pathology, 17 cases had marginal cord insertion (MCI), 13 cases had velamentous cord insertion (VCI), 5 cases had vasa previa (VP), and 2 cases had VCI combined with VP. The sensitivity and specificity of ultrasound diagnosis for APCIs were 59.5% (22/37) and 97.8% (394/403), respectively. The sensitivity and specificity of MRI diagnosis for APCIs were 86.5% (32/37) and 98.5% (397/403), respectively. Among the 37 cases of APCIs, prenatal MRI missed diagnosis of 2 cases of MCI, 2 cases of VCI, and misdiagnosed 1 case of VCI as an accessory placenta. MRI identified 10 cases of APCIs missed by ultrasound, including 5 cases of MCI, 2 cases of VP, 2 cases of VCI, and 1 case of combined VCI with VP. Additionally, ultrasound misdiagnosed 4 cases of APCIs, including 2 cases of VCI misdiagnosed as MCI and 2 cases of MCI misdiagnosed as VCI.Conclusions:For APCIs complicated with abnormalities of placental location or morphology, or placental accretion spectrum disease in late pregnancy, MRI has a higher diagnostic efficacy than ultrasound.

Objective:To investigate the contrast-enhanced ultrasound (CEUS) features of inflammatory hepatocellular adenoma (I-HCA).Methods:The contrast-enhanced ultrasound features I-HCA of 28 cases from April 2009 to November 2019 in Zhongshan Hospital, Fudan University were retrospectively analyzed, including arterial phase enhancement pattern, the homogeneity of enhancement, subcapsular enhancement, and the internal perfusion defect. All I-HCA lesions were divided into >5 cm group( n=9) and ≤5 cm group( n=19), the CEUS features between the two groups were compared. Results:All I-HCA lesions were hyper-enhanced in the arterial phase, among which 39.3% (11/28) showed diffuse filling, 39.3%(11/28) showed centripetal filling, and 21.4%(6/28) showed centrifugal filling pattern. Twenty-five percent (7/28) of I-HCAs showed heterogeneous enhancement, 10.7% (3/28) revealed unenhanced areas within the lesions. Subcapsular vessels were observed in 67.7 (21/31) of I-HCA lesions. Heterogeneous enhancement and unenhanced areas were more frequently detected in lesions >5 cm ( P=0.020, 0.026, respectively), while there was no difference in the enhancement pattern and subcapsular vessels between the two groups ( P>0.05). Inportal venous phase, 42.9%(12/28) of I-HCAs showed hypo-enhancement, and 57.1%(16/28) of lesions showed washout in late phase. According to "hyper-enhancement in arterial phase, sustained hyper- or iso-enhancement in portal venous and late phase" by CEUS, the diagnostic accuracy of benign lesion was 42.9%(12/28). According to any of hyper-enhancement pattern in arterial phase, subcapsular vascular enhancement, and sustained hyper- or iso-enhancement in portal venous and late phase, the diagnostic accuracy of I-HCA was 71.4% (20/28). Conclusions:CEUS is valuable in the diagnosis of inflammatory hepatocellular adenoma.

Objective: To analyze the characteristics of the "Interner Plus-based AIDS Comprehensive Prevention Service System" among MSM who frequently using the Internet in Guangzhou. Methods: An online survey was conducted among MSM who were recruited through gay-website portals between August and September, 2018 in Guangzhou, to collect information regarding the use of and attitudes on the "Interner Plus-based AIDS Comprehensive Prevention Service System" . Logistic regression was used to explore the association between the use of Internet intervention tools and related behavioral characteristics. Information on the awareness of AIDS, HIV testing, and condomless anal sex behavior were compared between the core or non-core services users. Results: A total of 777 Internet-based MSM were recruited as participants including 638 men (82.1%) as core service users. MSM were satisfied in using the the "Interner Plus-based AIDS Comprehensive Prevention Service System" while more than 80.0% of the users felt that the tools were helpful in: increasing the HIV awareness, promoting test uptake, and reducing those related risk behavior. Comparing with those who did not use the tools, the users showed higher rates in practising condomless anal intercourse (1.50-1.86 times), commercial sex with men (11.60-21.21 times), and unprotected vaginal intercourse (13.62-20.67 times), in the last 6 months. Proportions of core service users appeared as: [96.6% vs. 74.8%, aOR (95%CI): 8.80 (4.85-15.97)] on HIV testing, [56.4% vs. 22.3%, aOR (95%CI): 4.54 (2.94-7.02)] on regular HIV testing and [86.2% vs. 80.6%, aOR (95%CI): 1.75 (1.06-2.89)] on awareness of HIV knowledge respectively, which were all significantly higher than the non-core service users. Conclusions The frequent Internet using MSM in Guangzhou claimed to have had high acceptance and satisfaction on the local Internet HIV intervention service tools. The "Internet Plus-based AIDS Comprehensive Prevention Service System" had effectively reached the high-risk subgroups of MSM, increasing the awareness on related risk and promoting testing on HIV.

Objective: This article was to evaluate the applicability and feasibility of "Lingnanzhun" -an "Internet Plus-based HIV Self-testing Tool" targeting MSM in Guangzhou. Hopefully, the results could be used to improve the existing HIV testing services and to support the implementation and scale-up of HIV self-testing programs. Methods: Data were collected from a survey on HIV testing preferences among the Internet-using MSM in April to June, 2015. Univariate and multivariate logistic regression analysis were applied to identify factors associated with the use of HIV self-testing service provided by Lingnanzhun. Information related to the users of Lingnanzhun during September 2014 and December 2018 was also collected. Results: 769 MSM were recruited as participants. Of them, age distribution was 16-77(28.6±6.8) years old, 88.3%(679/769) were unmarried, 42.2%(325/769) were registered residents of Guangzhou, 82.1%(631/769) had university or college education. Among them, 195 (25.4%) used the HIV self- testing program of Lingnanzhun while 574 (74.6%) using the clinic service. Compared with the clinic service users, the Lingnanzhun users showed the following characteristics: longer experience in the MSM community ≥10 years (32.8% vs. 20.9%, 64/195 vs. 120/574); having male casual sexual partners ≥2 (42.1% vs. 29.6%, 82/195 vs. 170/574); having group sex (6.2% vs. 2.6%, 12/195 vs. 15/574) and having commercial sex with men (13.8% vs. 3.0%, 27/195 vs. 17/574). Data from the Lingnanzhun users showed that a total of 3 000 users had practised 5 038 times of self HIV-testings. 11.4% (343/3 000) of the Lingnanzhun users had never been tested. Conclusions It was applicable and feasible to provide Internet-based HIV self-testing service to MSM as a significant complement to the traditional facility-based HIV testing services. It was also useful in accessing those who were having higher risk or had never received HIV testing so as to increase the testing uptake and the frequency.

Objective: To analyze the characteristics of levels related to the risk through self-evaluation system, among MSM users in Guangzhou, between 2015 and 2017. Methods: Between 2015 and 2017, data was collected from the users of a self-evaluation system network related to HIV infection, based on the previous 'HIV health risk appraisal model’. Information on risk factors was collected to calculate the scores and levels of risks and to estimate the incidence of HIV. Taking the reference of R value on risks as (R=0.9-1.1) in general population. The ones with very low risk, with low risk, moderate risk, high risk and very high risk were set as R≤0.5, 0.5<R≤0.9, 0.9<R≤1.1, 1.1< R≤2.0 and R>2.0, respectively. The scores of modifiable risk factors were compared with different subgroups of MSM. Results: A total of 4 601 MSM were involved in this study, with the following features presented as: aged 16-64 (28.38±7.11) years, proportions of residence from Guangzhou, Guangdong province or other provinces as 38.6%(1 776/4 601)、35.4%(1 629/4 601) and 26.0%(1 197/4 601), 59.6%(2 742/4 601) received bachelor or above degrees. 81.3%(3 741/4 601) of them claimed as having homosexual orientation. R values of risk level on very low risk, low risk level, moderate risk, high risk and very high risk appeared as 12.9%(594/4 601), 50.9%(2 342/4 601), 17.0%(783/4 601), 14.8%(682/4 601) and 4.3%(200/4 601), respectively. Scores of modifiable risk factors decreased year by year (P<0.05), among MSM in this study. In either of the groups that experiencing insertive or receptive sex, the ones with heterosexual orientation presented the highest scores of modifiable risk factors (P<0.05). Conclusions The risk levels on HIV infections called for special attention among the users of the self-evaluation network system. Among the MSM that carrying either insertive or receptive sex role, the ones with heterosexual orientation had the highest risk levels and scores of modifiable risk factors in Guangzhou. Further study should be explored to better understand the causes of related risks.

Objective To investigate the epidemiological characteristics of outpatients exposed to rabies and to analyze the post-exposure prophylaxis in Weinan City in 2017 in order to provide a scientific basis for the prevention of rabies. Methods Clinical data of all outpatients with exposure to rabies in Wei-nan were collected. Ecxcel 2007 was used for data entry and SPSS13. 0 for Chi-square test. Results A total of 32 094 cases were reported with an annual exposure rate of 625. 64/100 000 in Weinan in 2017. Animal bites mainly occurred in spring and summer,accounting for 47. 47% of the total cases in 2017. There were statistically differences in exposure rate among different age groups (χ2=15. 858,P=0. 003). Farmers ac-counted for the largest proportion of the outpatients exposed to rabies (52. 34% ). Among 31 435 outpatients, 28 181(89. 65% ) received wound care and rabies vaccination. The vaccination rate of rabies immunoglobu-lin for patients with gradeⅢ exposure was 46. 93%. Conclusion Comprehensive measures with focuses on compulsory vaccination for domestic dogs and adoption of stray dogs should be implemented to prevent human rabies. Meanwhile,health education rabieson prevention and control should also be strengthened.

Objective To investigate the reasons and the methods of prevention and cure for serious complications of radiofrequency ablations in the treatments of hepatocellular carcinomas. Methods A total of 410 patients with BCLC at A or B stage of hepatocellular carcinomas in our hospital were enrolled between November 2014 and June 2009. These patients underwent a total of 504 times radiofrequency ablations for the treatments of liver lesions. This retrospective study analysed the reasons and the strategies of prevention and cure for the serious complications. Results In the patients with a total of 504 times radiofrequency ablations, 2 patients had massive hemorrhage caused by puncture injuries, 2 patients had the tumors which were close to the liver capsules and 1 patient had bile peritonitis caused by the injury of thermal ablation on the gallbladder. The maximum diameter of tumor was 5 cm. That tumor was close to the gallbladder. 2 patients had needle tract metastases caused by incompletely needle path ablations. 1 of the 2 patients had a tumor near the liver capsule, and the other patient had un-enough temperature for needle path ablation. Tumor outbreaks were happened in 2 patients. 1 of the 2 patients had a tumor which was located in the liver capsule and close to the portal vein. The other patient had a 12 cm diameter tumor with rich blood supplement. 2 patients had liver abscesses. 1 of the 2 patients had a tumor near the ascending colon, and the other patient had diabetes. 1 patient had colonic perforation caused by thermal ablation. The tumor in that patient was located in the right hepatic lobe segment and adjacent to the ascending colon. The incidence of serious complications was 1.98% (10/504). Conclusions The incidence of the serious complications of radiofrequency ablations for the treatments of hepatocellular carcinomas is relatively low. The main reasons for the serious complications were direct injuries caused by punctures, heat radiation injuries, tumors adjacent to large blood vessels, gallbladders and intestines, tumors with abundant blood supplement, needle paths fail to cross normal liver tissues, low scores of liver function, weak immune system and diabetes. The key points for avoiding and reducing the serious complications are preoperative evaluations of patients' basic situations, choices of appropriate puncture channels and control ranges of ablations when tumors are close to important blood vessels, intestines and gallbladders.