OBJECTIVE To investigate the clinical efficacy of integrating pharmacists into family health teams （FHTs） for long-term medication therapeutical management （MTM） in stroke patients， and empirically evaluate the service model. METHODS A pharmacist team， jointly established by clinical and community pharmacists from the Affiliated Suzhou Hospital of Nanjing Medical University （hereinafter referred to as “our hospital”）， developed a pharmacist-supported MTM model integrated into FHTs. Using a prospective randomized controlled design， 170 stroke patients discharged from our hospital （July 2022-December 2023） and enrolled in FHTs at Suzhou Runda Community Hospital were randomly divided into trial group （88 cases） and control group （82 cases） according to random number table. The control group received routine FHTs care （without pharmacist involvement in the team collaboration）， while the trial group xhz8405@126.com received 12-month MTM services supported by pharmacists via an information platform. These services specifically included innovative interventions such as personalized medication regimen optimization based on the MTM framework， dynamic medication adherence management， medication safety monitoring， a home medication assessment system， and distinctive service offerings. Outcomes of the 2 grousp were compared before and after intervention， involving medication adherence （adherence rate， adherence score）， compliance rates for stroke recurrence risk factors [blood pressure， low-density lipoprotein cholesterol （LDL-C）]， and incidence of adverse drug reactions （ADR）. RESULTS After 12 months， the trial group exhibited significantly higher medication adherence rates， improved adherence scores， higher compliance rates for blood pressure and LDL-C targets compared to the control group （P＜0.05）. The incidence of ADR in the trial group （4.55%） was significantly lower than that in the control group （8.11%）， though the difference was not statistically significant （P＞ 0.05）. CONCLUSIONS Pharmacist involvement in FHTs to deliver MTM services significantly enhances medication adherence and optimizes risk factor for stroke recurrence， offering practical evidence for advancing pharmaceutical care in chronic disease management under the family doctor system.

OBJECTIVE To explore the effects of meropenem exposure and degradation levels on clinical efficacy in patients with purulent meningitis （PM）. METHODS A total of 131 PM patients treated with meropenem at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2022 to June 2025 were prospectively included. Relevant data were collected and divided into a cured group （91 cases） and a non-cured group （40 cases） based on the efficacy. High-performance liquid chromatography-tandem mass spectrometry was used to determine the concentration of meropenem and its open-loop metabolites. Risk factors that affect efficacy were screened， and their predictive power and correlation were evaluated by univariate analysis， and multivariate Logistic regression analysis， receiver operating characteristic （ROC） curves， and correlation analysis. RESULTS Univariate analysis showed that serum creatinine， creatinine clearance rate， minimum inhibitory concentration of meropenem ≥16 μg/mL， cerebrospinal fluid red blood cell count， cerebrospinal fluid white blood cell count， cerebrospinal fluid glucose content， blood trough concentration， blood open-loop metabolite concentration/trough concentration ratio， and intrathecal injection were all correlated with efficacy （P＜0.05）. The results of multiple Logistic regression analysis showed that serum creatinine blood open-loop metabolite concentration/trough concentration ratio， intrathecal injection， and cerebrospinal fluid glucose content were influencing factors for suboptimal anti-infective ltt efficacy （P＜0.05）. ROC curve analysis showed that when the blood open-loop metabolite concentration/trough concentration ratio was greater than 2.854 （AUC＝0.647）， serum creatinine was less than 59.5 μmol/L （AUC＝0.647）， and cerebrospinal fluid glucose content was less than 3.37 mmol/L （AUC＝0.709）， the risk of treatment failure significantly increased （P＜0.05）. Correlation analysis showed that the blood trough concentration of meropenem was positively correlated with the concentration of its open-loop metabolites （R 2＝0.134 5， P＜0.000 1）. CONCLUSIONS Insufficient exposure level and rapid degradation of meropenem are key mechanisms affecting the anti-infective efficacy of PM. Elevated blood open-loop metabolite concentration/ trough concentration ratio， low serum creatinine level， lack of intrathecal injection， and low cerebrospinal fluid glucose content are independent risk factors for poor efficacy.

Objective:To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC).Methods:Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean.Results:The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean ( r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean ( r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without ( P=0.014). There were statistical differences in the Emeans among different types of pathological calcification ( P＜0.001). The multiple linear regression analysis showed that the lesion size ( β=0.325, P＜0.001), degree of fibrosis ( β=0.563, P＜0.001), psammoma bodies ( β=0.177, P=0.001), stromal calcification ( β=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma ( β=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions:The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

Objective:To explore the histopathological factors affecting the stiffness of papillary thyroid carcinoma (PTC).Methods:Ninety-six patients with PTC confirmed by surgery and pathology in Shanxi Bethune Hospital from January 2019 to December 2020 were selected, including 101 nodules. Two-dimensional ultrasound and shear-wave elastography (SWE) were performed before surgery and the average Young's modulus (Emean) of PTC nodules were measured. Histopathological examinations on the nodules were conducted after surgery to decide the lesion size, number of lesions, calcification type, presence or absence of capsular and extracapsular invasion, degree of fibrosis, microvessel density, and number of tumor cells. The correlations between the lesion size, degree of fibrosis, microvessel density, and number of tumor cells and the Emean were analyzed. The Emeans of nodules with different numbers of lesions, presence or absence of capsular and extracapsular invasion, and different pathological calcification types were compared. The multiple linear regression analysis was used to evaluate the histopathological factors influencing the Emean.Results:The ranges of the lesion sizes, degrees of fibrosis, microvascular density, numbers of tumor cells, and the Emeans of the 101 investigated PTC nodules were (1.29±0.95) cm, (30.64±18.37)%, (101.64±30.7) vessels per high power field, (373.52±149.87) cells per high power field, and (36.47±19.62) kPa, respectively. Correlation analysis showed that the lesion size of PTC and the degree of fibrosis were positively correlated with the Emean ( r=0.660, P＜0.001; r=0.789, P＜0.001), while the microvessel density was negatively correlated with the Emean ( r=-0.198, P=0.047). The Emean of the group with capsular and extracapsular invasion was higher than that of the group without ( P=0.014). There were statistical differences in the Emeans among different types of pathological calcification ( P＜0.001). The multiple linear regression analysis showed that the lesion size ( β=0.325, P＜0.001), degree of fibrosis ( β=0.563, P＜0.001), psammoma bodies ( β=0.177, P=0.001), stromal calcification ( β=0.164, P=0.003), and mixed calcification of both psammoma bodies and stroma ( β=0.163, P=0.003) were independent influencing factors for the Emean. The degree of fibrosis had the greatest impact on the Emean. Conclusions:The Emean of PTC lesions was correlated with the histopathological characteristics of PTC. The lesion size, degree of fibrosis, and calcification had significant impact on the Emean, among which the degree of fibrosis had the greatest impact.

Purpose: This study aims to evaluate the efficacy and safety of a new combination treatment of vinorelbine and pyrotinib in human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) and provide higher level evidence for clinical practice. Materials and Methods: This was a prospective, single-arm, phase 2 trial conducted at three institutions in China. Patients with HER2-positive MBC, who had previously been treated with trastuzumab plus a taxane or trastuzumab plus pertuzumab combined with a chemotherapeutic agent, were enrolled between March 2020 and December 2021. All patients received pyrotinib 400 mg orally once daily plus vinorelbine 25 mg/m2 intravenously or 60-80 mg/m2 orally on day 1 and day 8 of 21-day cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included the objective response rate (ORR), disease control rate (DCR), overall survival, and safety. Results: A total of 39 patients were enrolled. All patients had been pretreated with trastuzumab and 23.1% (n=9) of them had accepted trastuzumab plus pertuzumab. The median follow-up time was 16.3 months (95% confidence interval [CI], 5.3 to 27.2), and the median PFS was 6.4 months (95% CI, 4.0 to 8.8). The ORR was 43.6% (95% CI, 27.8% to 60.4%) and the DCR was 84.6% (95% CI, 69.5% to 94.1%). The median PFS of patients with versus without prior pertuzumab treatment was 4.6 and 8.3 months (p=0.017). The most common grade 3/4 adverse events were diarrhea (28.2%), neutrophil count decreased (15.4%), white blood cell count decreased (7.7%), vomiting (5.1%), and anemia (2.6%). Conclusion Pyrotinib plus vinorelbine showed promising efficacy and tolerable toxicity as second-line treatment in patients with HER2-positive MBC.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.
Humans ; Citric Acid/adverse effects* ; Prospective Studies ; Sodium Citrate ; Hemorrhage/chemically induced* ; Citrates/adverse effects* ; Anticoagulants/adverse effects* ; Renal Dialysis/adverse effects*

Objective: To evaluate the immunogenicity of group A+C meningococcal polysaccharide conjugate vaccine in infants under 2 years old. Methods: From March 2017 to June 2018, 1 932 healthy infants in Biyang County, Henan Province, who were not vaccinated with meningococcal meningitis vaccine and whose axillary temperature was ≤37.0 ℃, were recruited as participants. The 3 months and 6-11 months old infants were allocated to the experiment group and the control group in a ratio of 1∶1. Infants aged 12-23 months were allocated to the 1-dose group, the 2-dose group and the control group in a ratio of 1∶1∶1, with 276 infants in each group. The infants in the experiment group were intramuscularly injected with freeze-dried group A+C meningococcal polysaccharide conjugate vaccine to be evaluated, and infants in the control group received intramuscular injection of commercially available freeze-dried group A+C meningococcal conjugate vaccine. The venous blood of infants was collected 30 days before the first dose and after the last dose of inoculation, and the antibody seroconversion of each group was determined and compared. Results: The completion rate of immunogenicity study was 95.2% (1 839/1 932). Before inoculation, there was no statistical difference in the geometric mean titer and positive rate of group A+C antibodies between the experiment group and the control group in 3 months and 6-11 months old infants (all P values >0.05). The geometric mean titers and positive rate of group A antibodies in the 1-dose group were higher than those in the control group (all P values <0.05), but there was no statistical difference between the 2-dose group and the control group (all P values >0.05) in infants aged 12-23 months. After inoculation, the differences (95%CI) in the positive conversion rate of group A+C antibodies between the experiment group and the control group were -0.12% (-6.01%-5.77%) and 0.82% (-4.23%-5.86%) in the 3 months old infants. At the age of 6-11 months, the differences were 6.75% (1.71%-11.79%) and -4.32% (-8.73%-0.08%), respectively. At the age of 12-23 months, the differences were 1.02% (-3.80%-5.83%) and -4.40% (-7.79%- -1.01%) in the 2-dose group and -7.22% (-12.90%- -1.54%) and -18.61% (-23.75%- -13.46%) in the 1-dose group, respectively. The geometric mean titers of group A+C antibodies in the 3 months old infants were 48.50 and 63.12, respectively, which had no significant difference from the control group (43.02 and 57.99, respectively) (both P values <0.05). The geometric mean titers of group A+C antibodies in the 6-11 months and 12-23 months old infants were 84.09 and 92.51 (2-dose group), which were higher than those in the corresponding control group (43.10 and 61.83, respectively) (all P values <0.001). Conclusion: Group A+C meningococcal conjugate vaccine has good immunogenicity in infants under 2 years old.
Humans ; Infant ; Child, Preschool ; Meningococcal Vaccines ; Vaccines, Conjugate ; Vaccination ; Neisseria meningitidis ; Polysaccharides ; Antibodies, Bacterial

Objective:To investigate the human milk oligosaccharides (HMOs) levels in breast milk of mothers delivering preterm infants and their effects on the early growth and development of infants.Methods:In this prospective cohort study, full-term and preterm newborns whose parents decided to breastfeed were recruited from Peking University Third Hospital between December 1, 2017 and November 30, 2018. The preterm infants were divided based on their gestational ages into extremely preterm (<28 weeks), very preterm (28-31 +6 weeks) and moderate to late preterm (32-36 +6 weeks) groups. Breast milk was collected from mothers at 7, 14, 28 and 120d postpartum. 368 breast milk samples were collected from 125 mothers in this study, including 54 mothers of full-term infants, 23 mothers of moderate to late preterm infants, 39 mothers of very preterm infants, and 9 mothers of extremely preterm infants. Ultra-performance liquid chromatography-mass spectrometer (UPLC-MS/MS) was used to determine the concentration of 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), 3′-sialyllactose (3′SL), A-tetrasaccharide (P1), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose Ⅱ (LNFP-Ⅱ) and lacto-N-fucopentaose Ⅴ (LNFP-Ⅴ). Secretor status of mothers was defined as 2′-fucosyllactose (2′FL) concentration in colostrum and transitional milk greater than 200 μg/mL. Weight gain and the occurrence of allergic diseases of infants were collected at 120 d(4 months) postpartum. The chi-square test or the Fisher′s exact test was used for the comparison of categorical data between groups; Kruskal-Wallis test and Wilcoxon rank sum test were used for comparison of continuous data between groups. Nemenyi test was used for multiple comparison. Results:79.2% (99/125) of the mothers were secretor. There were no statistical differences between groups in the secretor status of mothers (χ2=1.31, P>0.05). The total concentration of HMOs peaked at 1-2 weeks postpartum. Compared to the preterm milk, the HMOs from the term milk was trending downwards at an earlier time. In the breast milk of secretor mothers on 28 d, total concentration of HMOs significant differed among the three groups of preterm milk and the term milk, with the median value of 4 587.09,4 615.25,5 277.44,5 476.03 μg/mL, respectively (Kruskal-Wallis χ2=8.1234, P=0.044). When analyzed by the median weight gain of the infants (low vs high weight gain) at 4 months postpartum, 2′FL was significantly lower in the high weight gain group at 7 d (1 818.04 μg/mL vs 2 181.67 μg/mL, W=1 386, P=0.018), while LNT & LNnT were significantly higher (1 182.36 μg/mL vs 1 053.62 μg/mL, W=816, P=0.044). The level of 3FL at 120 d was significantly affected by presence of allergic disease in infants, breast milk from mothers of infants with allergic disease had lower 3FL than those from mothers of infants without allergic disease (256.17 μg/mL vs 286.18 μg/mL, W=564, P=0.026). Conclusions:The overall profiles of HMOs in breast milk of mothers delivering preterm infants was basically the same as that of mothers delivering term infants; individual HMOs play a role in weight gain and the development of allergic diseases in preterm infants, but the mechanism is unclear and needs further study.

Objective:To investigate the human milk oligosaccharides (HMOs) levels in breast milk of mothers delivering preterm infants and their effects on the early growth and development of infants.Methods:In this prospective cohort study, full-term and preterm newborns whose parents decided to breastfeed were recruited from Peking University Third Hospital between December 1, 2017 and November 30, 2018. The preterm infants were divided based on their gestational ages into extremely preterm (<28 weeks), very preterm (28-31 +6 weeks) and moderate to late preterm (32-36 +6 weeks) groups. Breast milk was collected from mothers at 7, 14, 28 and 120d postpartum. 368 breast milk samples were collected from 125 mothers in this study, including 54 mothers of full-term infants, 23 mothers of moderate to late preterm infants, 39 mothers of very preterm infants, and 9 mothers of extremely preterm infants. Ultra-performance liquid chromatography-mass spectrometer (UPLC-MS/MS) was used to determine the concentration of 2′-fucosyllactose (2′FL), 3-fucosyllactose (3FL), 3′-sialyllactose (3′SL), A-tetrasaccharide (P1), lacto-N-tetraose (LNT), lacto-N-neotetraose (LNnT), lacto-N-fucopentaose Ⅱ (LNFP-Ⅱ) and lacto-N-fucopentaose Ⅴ (LNFP-Ⅴ). Secretor status of mothers was defined as 2′-fucosyllactose (2′FL) concentration in colostrum and transitional milk greater than 200 μg/mL. Weight gain and the occurrence of allergic diseases of infants were collected at 120 d(4 months) postpartum. The chi-square test or the Fisher′s exact test was used for the comparison of categorical data between groups; Kruskal-Wallis test and Wilcoxon rank sum test were used for comparison of continuous data between groups. Nemenyi test was used for multiple comparison. Results:79.2% (99/125) of the mothers were secretor. There were no statistical differences between groups in the secretor status of mothers (χ2=1.31, P>0.05). The total concentration of HMOs peaked at 1-2 weeks postpartum. Compared to the preterm milk, the HMOs from the term milk was trending downwards at an earlier time. In the breast milk of secretor mothers on 28 d, total concentration of HMOs significant differed among the three groups of preterm milk and the term milk, with the median value of 4 587.09,4 615.25,5 277.44,5 476.03 μg/mL, respectively (Kruskal-Wallis χ2=8.1234, P=0.044). When analyzed by the median weight gain of the infants (low vs high weight gain) at 4 months postpartum, 2′FL was significantly lower in the high weight gain group at 7 d (1 818.04 μg/mL vs 2 181.67 μg/mL, W=1 386, P=0.018), while LNT & LNnT were significantly higher (1 182.36 μg/mL vs 1 053.62 μg/mL, W=816, P=0.044). The level of 3FL at 120 d was significantly affected by presence of allergic disease in infants, breast milk from mothers of infants with allergic disease had lower 3FL than those from mothers of infants without allergic disease (256.17 μg/mL vs 286.18 μg/mL, W=564, P=0.026). Conclusions:The overall profiles of HMOs in breast milk of mothers delivering preterm infants was basically the same as that of mothers delivering term infants; individual HMOs play a role in weight gain and the development of allergic diseases in preterm infants, but the mechanism is unclear and needs further study.