OBJECTIVE To evaluate the therapeutic efficacy of 5 regimens of colistin sulfate for common Gram-negative bacilli infection based on pharmacokinetics （PK）/pharmacodynamics （PD） theory and Monte Carlo simulation. METHODS Minimal inhibitory concentration （MIC） data of colistin sulfate against Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumoniae， Escherichia coli and Enterobacter cloacae in 2023 were collected from the China Antimicrobial Resistance Surveillance System. Monte Carlo simulation was conducted with the ratio of the area under the concentration-time curve from 0 to 24 hours in the unbound state to the MIC （fAUC0－24 h/MIC） ≥15 as the target value， the probabilities of target attainment （PTA） of 5 regimens of colistin sulfate to achieve the target ratio were obtained at different MIC； and the expected population PTA， specifically the cumulative fraction of response （CFR）， for each regimen within a specific bacterial population was further calculated， to evaluate the therapeutic efficacy of the five colistin sulfate regimens. RESULTS When bacterial MIC≤0.5 µg/mL， PTA of all colistin sulfate regimens （500 000 IU， q12 h； 500 000 IU， q8 h； 750 000 IU， q12 h； 750 000 IU， q8 h； 1 000 000 IU， q12 h） were all more than 90%. When bacterial MIC＝1 µg/mL， PTA for regimen （750 000 IU， q8 h） against A. baumannii， K. pneumoniae， P. aeruginosa， E. coli and E. cloacae， and for regimen （1 000 000 IU， q12 h） against the other four bacterial species （excluding P. aeruginosa） remained above 90%. When bacterial MIC≥2 µg/mL， PTA of 5 colistin sulfate regimens were all lower than 90%. For E. coli， the CFR of only colistin sulfate regimen （500 000 IU， q12 h） was less than 90%； for K. pneumoniae， the CFR of only colistin sulfate regimen （750 000 IU， q8 h and 1 000 000 IU， q12 h） was greater than 90%； for the other three bacteria， CFR of 5 regimens were all less than 90%. CONCLUSIONS When the MIC of Gram-negative bacteria is less than 0.5 µg/mL， colistin sulfate regimen with a routine dose can be selected for treatment. When MIC was 1 µg/mL， an increase in the dosing amount or frequency is required. The empirical treatment of the other four bacterial infections excluding E. coli requires the use of off-label doses.

Objective This study aimed to assess the clinical efficacy of Shenling Baizhu Granules in treating low anterior resection syndrome(LARS)in rectal cancer.Methods The study employed a randomized,double-blind,placebo-parallel controlled,single-center,validity-tested clinical trial design.December 2019 to June 2022,the Department of Gastrointestinal Surgery and Integrated Traditional Chinese and Western Medicine of Peking University First Hospital recruited 110 patients who had undergone low anterior resection(LAR)for rectal cancer and subsequently developed LARS.These patients,meeting the enrollment criteria,were randomly assigned into the treatment group(55)and the control group(55)using the double-blind method principle.The randomization table was generated by SAS 9.2 software employing the double-blind method.The treatment group received oral Shenling Baizhu Granules,while the control group received oral placebo granules.Both groups commenced treatment on the 10th day after-surgery for 30 consecutive days.Patients were evaluated using LARS score,traditional Chinese medicine(TCM)symptom grading,and XU Zhongfa score before treatment,on the 15th day of treatment,and on the 1st day after treatment cessation.Results Out of 110 patients,107 were included in the full analysis set for efficacy analysis:55 patients in the treatment group and 55 patients in the control group.One case in the treatment group was excluded(against protocol),and two cases in the control group were excluded(one lost to follow-up,one against protocol).Baseline data between the two groups were consistent,with no statistically significant difference.Before treatment,LARS scores for the treatment and control groups were 33.0(31.0,36.0)and 34.0(32.0,37.0)respectively.Patients with TCM symptom scores of grades 2 to 3 accounted for 92.73％and 90.57％in the treatment and control groups,respectively,with no statistically significant difference.After 30 days of treatment,LARS scores for the treatment and control groups were 21.0(19.8,23.0)and 26.0(22.0,28.0)respectively.The percentage of patients with TCM symptom scores of grades 2 to 3 decreased to 33.33％in the treatment group and 66.04％in the control group,with a statistically significant difference.Shenling Baizhu Granules showed rapid improvement in watery or loose stools in post-operative rectal cancer patients.After 30 days of treatment,Shenling Baizhu Granules significantly improved appetite,stool consistency,abdominal distension,abdominal pain,and eructation symptoms in postoperative rectal cancer patients.Before treatment,the XU Zhongfa scores for the treatment and control groups were 3.0(2.0,4.3)and 4.0(2.0,4.0)respectively,with no statistically significant difference.After 30 days of treatment,the XU Zhongfa scores for the treatment and control groups were 7.0(6.0,8.0)and 6.0(5.0,7.0)respectively,with the treatment group significantly higher than the control group(P＜0.01).Conclusion Shenling Baizhu Granules can effectively improve LARS symptoms in patients following LAR of rectal cancer within a short period of time.

Glycogen storage disease type Ⅱ (GSDⅡ) is a rare autosomal recessive disorder.Infant onset of GSDⅡ usually accompanies progressive cardiac hypertrophy and muscle weakness, and eventually dies of cardiopulmonary failure.GSDⅡ is mainly screened and diagnosed by enzymatic and genetic tests.Enzyme replacement therapy (ERT) is the only currently approved treatment of GSDⅡ, which can effectively improve the function of the affected organs and the survival.Gene therapy and substrate reduction therapy for GSDⅡ are also undergoing basic or clinical research.This review summarizes the current research status of the diagnosis and treatment of GSDⅡ at home and abroad, focusing on the influencing factors for the efficacy of specific treatment (especially ERT), dosing regimen, and ways to improve the efficacy.

Objective To explore the value of curvature value of liver surface nodularity(LSN)based on MRI in evaluating liver function in patients with liver cirrhosis.Methods A retrospective analysis was made on the patients who underwent upper abdomen MR examination at 3.0T.The normal liver function patients and cirrhosis patients were enrolled in the study and then the Child-Pugh score of the patients were calculated.The patients were divided into three groups:normal liver group,compensated cirrhosis group and decompensated cirrhosis group.The water phase imaging of 3D modified Dixon fast field echo(mDixon-FFE)sequence was copied in DICOM format.ITK software was used to manually draw the full-thickness liver edge by two observers.The curvature value of LSN was obtained by using matlab self compiled code for follow up analysis.Kruskal-Wallis H test was used to compare the curvature value between the groups.The receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was obtained.Spearman test was used for the correlation analysis.Results The curvature values of LSN among the normal liver,compensated cirrhosis and decompensated cirrhosis groups gradually increased(P<0.05).Comparing normal liver with compensated cirrhosis,the AUC of diagnosing compensated cirrhosis was 0.84,with the sensitivity of 72.7%and the specificity of 89.3%.Comparing compensated cirrhosis with decompensated cirrhosis,the AUC of diagnosing decompensated cirrhosis was 0.91,with the sensitivity of 80%and the specificity of 90.9%.There was a moderate positive correlation between the curvature value of LSN and liver function score in patients with cirrhosis(r=0.63,P=0.002).Conclusion The curvature value of LSN based on MRI can be used for preliminary evaluation of liver function of liver cirrhosis,with the AUC more than 0.80 and higher sensitivity and specificity.

Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Objective To investigate the current status of radiation protection in non-medical radiation workplaces in Yantai, China, and to provide a scientific basis for occupational health management in non-medical radiation workplaces. Methods Non-medical radiation workplaces in Yantai were investigated using a questionnaire survey in 2022, including radiation source term, occupational health examination, personal dose monitoring, personal protective equipment, and radiation protection testing workplaces. Data were entered by a double-entry method and then analyzed. Results There were 56 non-medical radiation workplaces in Yantai, covering manufacturing, nonferrous metal ore mining, nuclear power plant, transportation, and technical services. There were 0 Class I radiation device, 150 Class II radiation devices, and 10 Class III radiation devices; there were 80 Class I radiation sources, 16 Class II radiation sources, 14 Class III radiation sources, 62 Class IV radiation sources, and 135 Class V radiation sources. There were 998 radiation workers, with an occupational health examination rate and personal dose monitoring rate of 98.3%. Among the 56 non-medical radiation workplaces, 47 (83.9%) were equipped with radiation protection monitoring instruments, 24 (51.1%) workplaces had verified the radiation protection monitoring instruments, with 2017 personal dose monitoring instruments and 2327 personal protective equipment in place, 42 (75%) workplaces carried out occupational health assessments, 44 (78.6%) workplaces carried out self-detection, and 53 (94.6%) workplaces carried out entrusting detections (monitoring pass rate: 100% [53/53]). The declaration rate of occupational hazard items was 87.5% (49/56). Conclusion There is still a gap between the current status and the requirements in the national regulations and standards regarding radiation protection in non-medical radiation workplaces. Therefore, the supervision and management of non-medical radiation workplaces should be further strengthened, especially the configuration and verification of radiation protection monitoring instruments.

Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective To investigate the effect of Kaixinsan(KXS,a traditional Chinese medicine formula)for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism.Methods Forty female BALB/c mice were randomized equally into control group,model group,and low-and high-dose KXS treatment groups,and in the latter 3 groups,mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage.Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test,and the changes in serum levels of depression-related factors were examined.RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS.The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control.Results KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models.RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress,lipid metabolism and iron ion binding in the prefrontal cortex.Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice.In SH-SY5Y cells,both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis.Conclusion KXS alleviates adriamycin-induced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

Objective:To analyze the diagnosis and treatment of children with rare diseases in the pediatric intensive care unit (PICU), the distribution of disease types and populations, clinical characteristics, and the use of orphan drugs.Methods:A retrospective case summary was conducted. Data were collected from 105 children aged 29 days to <18 years with a confirmed diagnosis of rare diseases according to the "First Batch of Rare Disease Catalogue in China" who were admitted to the PICU of Beijing Children′s Hospital, Capital Medical University from January 2020 to December 2022. Data including general information, auxiliary examinations, and treatment details for each patient were collected from the hospital′s electronic medical record system. Patients were divided into age groups: infancy (29 days to<1 year), early childhood (1 to <3 years), preschool age (3 to<7 years), school age (7 to<13 years), and adolescence (13 to<18 years) . The chi-square test was used to compare gender distribution differences among various rare diseases. Results:A total of 105 patients with 130 cases meeting the diagnostic criteria were included, accounting for 4.7% (130/2 754) of the total admissions to the PICU. The age at PICU admission was 5.3 (0.8, 9.5) years and there were 81 cases in male. The 3 most common types of diseases were endocrine, nutritional, and metabolic diseases (37 cases); followed by neurological disorders(32 cases); and congenital malformations, deformities, and chromosomal abnormalities(17 cases). The 5 most common rare diseases were methylmalonic acidemia (14 cases), mitochondrial encephalomyopathy (14 cases), atypical hemolytic uremic syndrome (12 cases), autoimmune encephalitis (12 cases), and idiopathic cardiomyopathy (9 cases). The distributions of common rare diseases varied among different age groups. In infants, atypical hemolytic uremic syndrome was most common (6 children). There was no statistically significant difference regarding gender among children with mitochondrial encephalomyopathy (13.6% (11/81) vs. 6.1% (3/49), χ2=1.77, P=0.184). Respiratory failure (36 cases) was the primary reason for rare diseases children to be admitted to the PICU. A total of 95 cases underwent mechanical ventilation, 39 cases received multidisciplinary collaborative diagnosis and treatment, and only 6 children received orphan drug therapy during their stay in the PICU. Conclusions:Rare diseases are not uncommon in PICU. Endocrine, nutritional and metabolic disorders, neurological disorders, congenital malformations, deformities, and chromosomal abnormalities were common. Methylmalonic acidemia, mitochondrial encephalomyopathy, atypical hemolytic uremic syndrome and autoimmune encephalitis have higher cases. Many children with rare diseases in the PICU have complex conditions those are challenging to treat, requiring multidisciplinary collaboration. The utilization rate of orphan drugs among children with rare diseases in PICU needs to be improved.

Objective:To summarize and analyze the clinical characteristics, treatment and prognosis of glycogen storage disease type Ⅱ(GSD Ⅱ) patients admitted to pediatric intensive care units(PICU), and to improve the pediatricians' understanding of children with severe GSD Ⅱ.Methods:Children with GSD Ⅱ admitted to PICU at Beijing Children's Hospital of Capital Medical University between January 2010 and December 2021 were included. Patient's data were collected through the electronic medical record system.After the patient was discharged,telephone follow-ups were conducted regularly for over a year.Results:A total of eight patients with a median age of 30.5 months were included. There were four patients with infantile GSD Ⅱ, whose median age of onset was 5.5 months. There were four patients with late-onset GSD Ⅱ, whose median age of onset was 36.0 months. Eight patients required continuous noninvasive/invasive respiratory support. Three patients with infantile GSD Ⅱ required respiratory support within one month of onset, and three patients with late onset GSD Ⅱ required respiratory support within one year of onset. A total of six patients had cardiac arrest during the course of the disease. One patient was regularly treated with enzyme replacement therapy during hospitalization but his condition did not improve significantly. Three patients were discharged following medical advice,including one patient continuing noninvasive respiratory support after discharge, and two patients requiring onging invasive respiratory support.A total of four children died,including one being an in-hospital death,and three occuring within one year after hospital discharge. A total of 14 genotypes were detected in eight patients, of which three were newly discovered gene mutations.Conclusion:The children with GSD Ⅱ admitted to PICU have severe respiratory dysfunction and need continuous respiratory support during the early stage of the disease. The incidence of cardiopulmonary arrest caused by infection and respiratory muscle weakness is high. It is recommended to closely monitor the lung function and cardiac function of such children, and actively give the prevention and treatment of infectious diseases. Whether enzyme replacement therapy can benefit patients with severe GSD Ⅱ and whether the newly identified mutations correlate with disease severity needs to be further evaluated.