Objective To evaluate the bioequivalence of oral sidenafil citrate tablets manufactured(100 mg)test preparations and reference preparations in healthy subjects under fasting and fed conditions.Methods Using a single-dose,randomized,open-lable,two-period,two-way crossover design,36 healthy subjects respectively for fasting and fed study were enrolled,and randomized into two groups to receive a single dose of test 100 mg with 7-day washout period.Plasma concentration of sidenafil and N-demethylsildenafil was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.The pharmacokinetic parameters were calculated by Analyst 1.6.3(AB Scie)using non-compartmental model,and bioequivalence evaluation was performed for the two preparations.Relevant safety evaluations were performed during the trial.Results The main pharmacokinetic parameters of sidenafil after a single oral dose of sidenafil citrate tablets under fasting condition for test and reference were as follows:Cmax were(494.69±230.94)and(558.78±289.83)ng·mL-1,AUC0-t were(1 336.21±509.78)and(1 410.82±625.99)h·ng·mL-1,AUC0-were(1 366.49±512.16)and(1 441.84±628.04)h·ng·mL-1,respectively.The main pharmacokinetic parameters of sidenafil under fed condition for T and R were as follows:Cmax were(381.89±126.53)and(432.47±175.91)ng·mL-1,AUC0-t were(1 366.34±366.99)and(1 412.76±420.37)h·ng·mL-1,AUC0-were(1 403.28±375.32)and(1 454.13±429.87)h·ng·mL-1,respectively.The results demonstrated the bioequivalence of sidenafil citrate tablets between T and R.The incidence of adverse events in fasting and fed tests were 33.33％and 25.00％,respectively.No serious adverse event was reported.Conclusion The test and reference formulation of sidenafil citrate tablets were equivalent and was safe.

A rich diversity of wild medicinal plant resources is distributed in China, but the breeding of new plant varieties of Chinese medicinal plants started late and the breeding level is relatively weak. Chinese medicinal plant resources are the foundation for new varieties breeding, and the plant variety rights(PVP) are of great significance for the protection and development of germplasm resources. However, most Chinese medicinal plants do not have a distinctness, uniformity, and stability(DUS) testing guideline. The Ministry of Agriculture and Rural Affairs has put 191 plant species(genera) on protection lists, of which only 30 are medicinal species(genera). At the same time, only 29 of 293 species(genera) plants in the Protection List of New Plant Varieties of the People's Republic of China(Forest and Grass) belong to Chinese medicinal plants. The number of PVP applications and authorization of Chinese medicinal plants is rare, and the composition of variety is unreasonable. Up to now, 29 species(genera) of DUS test guidelines for Chinese medicinal plants have been developed. Some basic problems in the breeding of new varieties of Chinese medicinal plants have appeared, such as the small number of new varieties and insufficient utilization of Chinese medicinal plant resources. This paper reviewed the current situation of breeding of new varieties of Chinese medicinal plants and the research progress of DUS test guidelines in China and discussed the application of biotechnology in the field of Chinese medicinal plant breeding and the existing problems in DUS testing. This paper guides the further application of DUS to protect and utilize the germplasm resources of Chinese medicinal plants.
Agriculture ; Biotechnology ; Plant Breeding ; Plants, Medicinal/genetics*

Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group (P<0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope (P<0.01), but had no significant effect on the ECAP latency (P>0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.
Child, Preschool ; Female ; Humans ; Infant ; Male ; Cochlea ; Cochlear Implantation/methods* ; Cochlear Implants ; Cochlear Nerve ; Electric Stimulation ; Evoked Potentials, Auditory/physiology*

OBJECTIVE: To study the effect of ultrasound-guided fascia iliaca compartment block on perioperative analgesia and postoperative complications in geriatric patients with hip fractures. METHODS: A total of 127 elderly patients undergoing hip fracture surgery from January 2021 to September 2021 were randomized to receive ultrasound-guided continuous fascia iliaca compartment block(group F) either intravenous analgesia control group(group C). There were 62 cases in group F, including 19 males and 43 females with an average age of (82.4±7.2) years old ranging from 66 to 95 years old, involving 25 femoral neck fractures and 37 femoral intertrochanteric fractures. There were 65 cases in control group, including 18 males and 47 females, with an average age of (81.4±8.7) years old ranging from 65 to 94 years old, involving 29 femoral neck fractures and 36 femoral intertrochanteric fractures. The visual analogue scale(VAS), minimental state examination (MMSE), observer's assessment of alertness/sedation(OAA/S) scale, modified Bromage score, postoperative complications and general conditions during hospitalization in two groups were observed. RESULTS: The resting and exercise VAS at 30 min after block, anesthesia placement and 6, 24 and 48 h after surgery were lower than those in group C(P<0.05). In group F, MMSE scores at 12 h before surgery, and 1, 3 d after surgery and OAA/S scores at 3 d after surgery were higher than those in group C(P<0.05). The incidence of adverse effects and the number requiring additional analgesia were lower than those in group C(P<0.05). Group F had better perioperative analgesia satisfaction and hospital stay than group C(P<0.05). But there was no significant difference regarding Bromage score and 30-day mortality between two group(P>0.05). CONCLUSION Ultrasound-guided continuous fascia iliacus space block was safe and effective for elderly patients with hip fracture, and could significantly reduce perioperative pain, improve postoperative cognitive function, and reduce postoperative complications, thereby shortening hospital stay and improving the quality of life during hospitalization.
Male ; Female ; Humans ; Aged ; Aged, 80 and over ; Pain Management ; Nerve Block ; Quality of Life ; Hip Fractures/surgery* ; Pain/surgery* ; Femoral Neck Fractures/surgery* ; Femoral Fractures/surgery* ; Ultrasonography, Interventional ; Postoperative Complications/surgery* ; Fascia ; Pain, Postoperative

OBJECTIVE: The relationship between sodium intake and cardiovascular (CV) events remains unconfirmed. Therefore, we carried out a systematic review and dose-response meta-analysis for evaluating the potential impact of 24-hour sodium excretion on CV risk. Besides, 24-hour sodium excretion was used to replace daily sodium diet intake. METHODS: We searched ISI Web of Science, Embase, PubMed, and the Cochrane Library. Our study included cohort studies reporting hazard ratio ( HR). The random-effects model was used for summarizing the total relative risks ( RRs) between the included studies. In addition, the generalized least-squares regression was employed to fit the study model. RESULTS: A total of 9 studies involving 645,006 participants were included in this study. A significant non-linear relationship was observed between sodium excretion and CV events ( P _{non-linearity} < 0.001). In studies collecting 24-h urine samples, the sodium excretion and CV events risk were associated linearly ( RR: 1.04; 95% CI: 1.01, 1.07). CONCLUSION In a linear dose-response manner, every 1 g increase in sodium intake was associated with an increased risk of CV events up to 4%. Further studies are required to validate our conclusions further.
Humans ; Urinalysis ; Sodium Radioisotopes ; Cardiovascular Diseases/epidemiology* ; Sodium, Dietary/adverse effects*

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 μm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/standards* ; Quality Control

Objective: To analyze the temporal bone CT and inner ear magnetic resonance imaging characteristics of cochlear implant patients with no cochlear nerve display in the inner auditory canal under MRI. To retrospectively analyze the long-term hearing and speech rehabilitation effects of such patients after cochlear implant. And to analyze the correlation between the results of imaging examinations and the postoperative effects of cochlear implant patients with this type of cochlear nerve deficiency. Methods: A total of 88 children with cochlear nerve deficiency, who underwent cochlear implantation in Shandong Provincial ENT Hospital from May 2014 to October 2018, were enrolled. Patients with cochlear malformations were excluded,only the patients with cochlear nerve deficiency whose cochlear structure was normal and no cochlear nerve displayed in inner auditory canal under MRI were enrolled. There were 64 patients, including 4 bilaterally implanted, 68 ears in total, with an average age of (2.8±1.7) years (range 1-6 years) at the time of implantation. The implanted product was Cochlear, including 24RECA and 512 models. All patients underwent inner ear magnetic resonance imaging and temporal bone CT scan before operation. Auditory speech function assessments were performed at 12 months, 24 months, and 36 months after surgery, including categories of auditory performance (CAP), speech intelligibility rating (SIR) and hearing aid threshold test. The imaging evaluation content included the width of the cochlear nerve canal of temporal bone CT, the width of the internal auditory canal, the width of the auditory nerve at the cerebellopontine angle of the inner ear MRI, and the ratio of the facial nerve to the width of the auditory nerve at the cerebellopontine angle. The correlations between the results of postoperative hearing aid hearing threshold, CAP, SIR and imaging results were analyzed. Results: Among the 64 cases of cochlear nerve not shown under MRI, 56 ears with CT data showed that the width of the cochlear nerve canal in temporal bone CT was (0.72±0.30) mm (mean±standard deviation, the same below), and the width of the internal auditory canal was (4.07±1.10) mm; 66 ears with MRI data showed that the diameter of the auditory nerve at the cerebellopontine angle of the inner ear MRI was (1.58±0.27) mm, the diameter of the facial nerve was (1.57±0.27) mm, and the ratio of the diameter of the facial nerve to the auditory nerve was (1.02±0.23). The average hearing thresholds at 12, 24, and 36 months after surgery were (46.8±2.5) dB HL, (40.7±0.8) dB HL, and (36.8±1.5) dB HL, respectively. The preoperative and postoperative CAP scores at 12, 24 and 36 months were (1.0±1.0), (3.8±1.4), (4.5±1.4) and (5.1±0.7) points, respectively. The preoperative and postoperative SIR scores at 12, 24, and 36 months were (1.1±0.3), (1.9±0.9), (2.5±0.9), and (2.9±0.6) points, respectively. The hearing threshold at 24 months after surgery was negatively correlated with the width of the internal auditory canal of temporal bone CT (r=-0.349, P=0.037), and the hearing threshold at 36 months after surgery was positively correlated with the ratio of the diameter of the facial nerve to the auditory nerve at the cerebellopontine angle of the inner ear MRI (r=0.740, P=0.001). Conclusions: Children with cochlear implants whose cochlear nerves are not shown on MRI can benefit from cochlear implantation, and their speech and auditory functions can improve significantly after surgery. The width of the internal auditory canal in the temporal bone CT and the ratio of the diameter of the facial nerve to the auditory nerve at the cerebellopontine angle of the inner ear MRI may be related to the long-term hearing threshold after surgery.
Child ; Child, Preschool ; Cochlear Implantation ; Cochlear Implants ; Cochlear Nerve/diagnostic imaging* ; Hearing Loss, Sensorineural/surgery* ; Humans ; Infant ; Magnetic Resonance Imaging ; Prognosis ; Retrospective Studies ; Speech Intelligibility

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

OBJECTIVE: To the clinical characteristics and prognostic value of the patients with complete deletion of TET_JBP domain (ΔJBP) in TET2 acute myeloid leukemia (AML). METHODS: Next Generation Sequencing technology was used to determine the mutations of 34 AML-related genes (including TET2 gene). The I-TASSER tool was used to predict the tertiary structure of the full-length TET2 protein and TET_JBP structure deletion. RESULTS: Among 38 AML patients with TET2 mutations, 22(57.9%) showed truncation mutations, of which 16 (72.7%) produced TET2ΔJBP truncation mutants. Protein structure prediction showed that the deletion of TET_JBP domain lead to the significant changes of tertiary structure in TET2 protein. Compared with the patients in non-ΔJBP group, the age of patients in ΔJBP group were older (63 vs 54 years old, P=0.047), and the occurrence rate of CEBPA double mutation (CEBPA CONCLUSION AML patients with TET2ΔJBP truncation mutant shows lower CR rate, shorter EFS and OS after induction chemotherapy, which may be related to the poor prognosis, and co-mutation with CEBPA
DNA-Binding Proteins/genetics* ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Prognosis ; Proto-Oncogene Proteins/genetics* ; Remission Induction

Objective: : Shunt infection is a common complication while treating hydrocephalus. The antibiotic-impregnated shunt catheter (AISC) was designed to reduce shunt infection rate. A meta-analysis was conducted to study the effectiveness of AISCs in reduction of shunt infection in terms of age, follow-up time and high-risk patient population. Methods: : This study reviewed literature from three databases including PubMed, EMBASE, and Cochrane Library (from 2000 to March 2019). Clinical studies from controlled trials for shunt operation were included in this analysis. A subgroup analysis was performed based on the patient’s age, follow-up time and high-risk population. The fixed effect in RevMan 5.3 software (Cochrane Collaboration) was used for this meta-analysis. Results: : This study included 19 controlled clinical trials including 10105 operations. The analysis demonstrated that AISC could reduce the infection rate in shunt surgery compared to standard shunt catheter (non-AISC) from 8.13% to 4.09% (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.40–0.58; p=0.01; I2=46%). Subgroup analysis of different age groups showed that AISC had significant antimicrobial effects in all three groups (adult, infant, and adolescent). Follow-up time analysis showed that AISC was effective in preventing early shunt infections (within 6 months after implant). AISC is more effective in high-risk population (OR, 0.24; 95% CI, 0.14–0.40; p=0.60; I2=0%) than in general patient population. Conclusion : The results of meta-analysis indicated that AISC is an effective method for reducing shunt infection. We recommend that AISC should be considered for use in infants and high-risk groups. For adult patients, the choice for AISC could be determined based on the treatment cost.