ObjectiveTo investigate the value of baseline red cell distribution width （RDW） and alkaline phosphatase （ALP） level after ursodeoxycholic acid （UDCA） treatment for one month in predicting the response to UDCA treatment in patients with primary biliary cholangitis （PBC）. MethodsA retrospective analysis was performed for the data of 127 patients with PBC who were diagnosed in Department of Hepatology， The Third People’s Hospital of Jiangsu University， from January 2015 to July 2022， with data collected at baseline， after one month of treatment， and after one year of follow-up. Based on the Paris-I criteria， the patients were divided into good response group and poor response group， and the two groups were analyzed in terms of clinical and laboratory features and their association with response to UDCA. The Logistic regression method was used to investigate the independent risk factors for response to UDCA treatment. The area under the ROC curve （AUC） was used to determine the optimal cut-off values of related indicators； the patients were divided into two groups based on such values， and the two groups were compared in terms of baseline indicators and response. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. ResultsCompared with the good response group， the poor response group had significantly higher levels of total bilirubin， aspartate aminotransferase/alanine aminotransferase， ALP， RDW， and RDW-CV at baseline and a significantly higher level of ALP after one month of UDCA treatment （Z=-4.792， -3.697， -2.399， -4.102， -3.220， and -4.236， all P<0.05）. Compared with the good response group， the poor response group had significantly lower levels of albumin， hemoglobin， lymphocytes， hematocrit， and body mass index at baseline （Z=-3.592， -3.603， -2.602， -3.829， -2.432， all P<0.05）， as well as significantly lower levels of prealbumin， albumin/globulin ratio， apolipoprotein A， and free triiodothyronine at baseline （t=4.530， 3.402， 3.485， and 3.639， all P<0.001）. Compared with the poor response group， the good response group had a significantly lower proportion of patients with liver cirrhosis， gallstones/cholecystitis， or anemia （χ²=20.815， 3.892， and 12.283， all P<0.05）. Baseline RDW （odds ratio ［OR］=1.157， 95% confidence interval ［CI］： 1.028‍ — ‍1.301， P=0.015） and ALP level after one month of treatment （OR=1.012， 95%CI： 1.005‍ — ‍1.020， P=0.002） were independent risk factors for response to UDCA， with an AUC of 0.713 and 0.720， respectively. The patients with baseline RDW≥upper limit of normal （ULN） and ALP≥2.2×ULN after one month of UDCA treatment had a lower UDCA response rate （42.6% vs 8.2%， χ²=20.813， P<0.001）. ConclusionPatients with baseline RDW≥ULN and ALP≥2.2×ULN after one month of UDCA treatment tend to have a low biochemical response rate to UDCA.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.

OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.

OBJECTIVE To study the pharmacokinetics of Esketamine hydrochloride nasal spray in rats and ciliary toxicity to maxillary mucosa of bullfrog. METHODS The plasma concentration of esketamine hydrochloride in rats was determined by LC-MS/ MS after intravenous injection of esketamine hydrochloride solution and nasal administration of esketamine hydrochloride； the pharmacokinetic parameters were calculated by using Phoenix WinNonlin 8.1.0 software. Using the maxillary mucosa of isolated bullfrog as a model， the morphological changes of maxillary mucosa were investigated， and the duration and recovery of ciliary oscillation were recorded after nasal administration of esketamine hydrochloride. RESULTS The peak of blood concentration occurred 2 min after nasal administration of esketamine hydrochloride； cmax was （814.58±418.80） ng/mL， AUC0－∞ was （203.75± 92.76） ng·h/mL， and the absolute bioavailability was 60.68%. After nasal administration of esketamine hydrochloride， it was observed that the cilia of bullfrog were arranged neatly， the edges were clear， the cilia tissue structure was complete and the cilia moved actively. The cilia movement time was （178.17±13.30） min for the first time， and after the cilia moved again， the ciliary movement time measured again was （24.50±9.19）min with a relative movement percentage of 53.56%. CONCLUSIONS Esketamine hydrochloride nasal spray has a rapid onset of action， high bioavailability， and low ciliary toxicity.

This experiment aims to study the taste-masking effects of different kinds of corrigent used individually and in combination on ibuprofen oral solution, in order to optimize the taste-masking formulation. Firstly, a wide range of corrigent and the mass fractions were extensively screened using electronic tongue technology. Subsequently, a combination of sensory evaluation, analytic hierarchy process (AHP)-fuzzy mathematics evaluation, and Box-Behnken experimental design were employed to comprehensively assess the taste-masking effects of different combinations of corrigent on ibuprofen oral solution, optimize the taste-masking formulation, and validate the results. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine (ethical code: 2024BZYLL0102). The results showed that corrigent fractions and types were screened separately through single-factor experiments. Subsequently, a Box-Behnken response surface design combined with AHP and fuzzy mathematics evaluation was used to fit a functional model: Z = 688.310 11 - 3 023.722 22X₁ - 11.477 00X₂ + 62.721 67X₃ + 14.600 00X₁X₂ - 179.666 67X₁X₃ - 3.152 00X₂X₃ + 4 031.111 11X₁² + 0.525 28X₂² + 9.772 00X₃². This model is stable and reliable, determining the optimal taste-masking formulation to be 3.9 g·L^-1 of stevioside, 100 g L^-1 of xylitol, and 30 g L^-1 of methyl-β-cyclodextrin. The comprehensive score of the verification test is 88.14, with a relative RSD of 0.39%, indicating the feasibility of this model. This study achieved the improvement of the taste of ibuprofen oral solution through a combination of objective and subjective methods. Three types of corrigent were identified for enhancing drug taste, leading to the selection of the optimal taste-masking formulation for ibuprofen oral solution. This significantly enhanced the taste of the original formulation, improved patient compliance, and offered a new approach to mitigating the undesirable taste of formulations.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To observe the value of right ventricle modified myocardial performance index(RV-Mod-MPI)for evaluating maternal obstetric antiphospholipid syndrome(OAPS)involving fetal right ventricular function.Methods Forty-five pregnant women with maternal OAPS(OAPS group)and 60 healthy pregnant women(control group)were prospectively enrolled.Fetal RV-Mod-MPI was obtained with tricuspid and pulmonary valve flow images by applying pulsed wave Doppler(PW).Late pregnancy conditions and data of newborns after delivery were recorded.The indexes were compared between groups.Receiver operating characteristic curve was drawn,and the area under the curve(AUC)was used to assess the efficacy of fetal RV-Mod-MPI for predicting adverse pregnancy outcomes in OAPS group.Results Compared with those in control group,OAPS group had higher fetal RV-Mod-MPI values,lower newborn birth weight and lower Apgar score at 1 min after birth,as well as higher probability of adverse pregnancy outcomes(all P＜0.05).The AUC of fetal RV-Mod-MPI for predicting adverse pregnancy outcome in OAPS group was 0.726.Conclusion RV-Mod-MPI could be used to evaluate maternal OAPS involving fetal right ventricular function and predict adverse pregnancy outcomes.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.

Objective:To investigate the relationship between the number of removed lymph nodes(RLN)and patient prognosis during radical surgery for extensive cervical cancer(CC).Methods:Clinical data of 21416 pa-tients with CC who underwent radical hysterectomy between January 1,2004 to August 31,2018 in the Chinese Cervical Cancer Clinical Study was retrospectively reviewed.Restricted cubic spline(RCS)was used to analyze the dose-response relationship between the number of RLN and prognosis.The patients were divided into three groups according to the RCS and RLN number:1-17 group(8733 cases),18-26 group(8189 cases),and≥ 27 group(4494 cases).Kaplan-Meier survival analysis and Log-Rank tests were used to compare the OS rates and DFS rates between groups at 3 and 5 years.Multivariate Cox proportional hazards model was used to analyze the prognostic mortality risk.Results:① RCS results showed a U-shaped nonlinear dose-response relationship be-tween the number of RLN and prognosis(P＜0.01).When the number of RLN was less than 26,the risk of death decreased as the number of RLN increased,and the risk was lowest when the number of RLN was 26.②There were statistically significant differences(P＜0.05)in age,histological type,tumor diameter,nerve invasion,uterine invasion,vaso-lymph node space invasion,cervical invasion,number of lymph node metastasis,whether preopera-tive adjuvant therapy was received,postoperative adjuvant therapy,and whether postoperative adjuvant therapy was standardized among the 3 groups(P＜0.05).③Kaplan-Meier survival curve analysis showed that the 5-year OS of the 1-17 group,18-26 group,and ≥ 27 group were 90.23％,92.28％,and 91.61％,respectively,and the 5-year DFS were 85.32％,87.90％,and 87.18％,respectively.The differences between the three groups were sta-tistically significant(P＜0.01).④The results of multivariate Cox regression analysis showed that RLN number in the range of 1-17 was a significant risk factor for the 3-and 5-year OS and DFS,when compared to the 18-26 RLN group(HR＞1,P＜0.05).Conclusions:RLN number may be one of the prognostic indicators of CC.When the number of RLNs is between 18-26,the prognosis of the patient may be better.The number of RLN in the range of 1-17 may increase the risk of recurrence or death in CC patients.