To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Objective To evaluate the predictive value of dose-surface histogram(DSH)for radiation proctitis(RP)in prostate cancer(PCa)patients undergoing radiotherapy.Methods This prospective randomized controlled clinical trial included 380 PCa patients who underwent image-guided radiotherapy in the First Affiliated Hospital of Hebei Northern University from January 2018 to January 2023.Patients were randomly divided into observation group(n=200)and control group(n=180).The rectal dose distribution of patients in the two groups was evaluated by using DSH and dose-volume histogram(DVH),respectively.The receiver operating characteristic(ROC)curve was utilized to evaluate the predictive value of DSH for acute RP,with DVH serving as a reference.Results The difference was not statistically significant in clinical information such as age,KPS score,and body mass index(BMI)between the observation and control groups(P＞0.05),as well as in acute RP incidence(P＞0.05).There were significant differences in S40 and V40,S50 and V50,S60 and V60,S70 and V70,and S78 and V78 between the two groups(P＜0.05).S40,S50,V40,and V50 showed low efficacy(P＜0.001)in predicting acute RP at each level,with AUC≤0.700.S60 and V60 showed moderate efficacy(P＜0.001)in predicting acute RP at each level,with AUC 0.700-0.900.S70,S78,V70 and V78 showed high efficacy(P＜0.001)in predicting acute RP at each level,with AUC＞0.900.Conclusions The predictive value of DSH for rectal toxicity in patients with PCa is basically consistent with that of DVH.It is expected to become a novel and valuable tool for evaluating radiotherapy plans in the future.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

To meet the domestic clinical demand timely,the national health commission has released three batches of encourage generic drug catalogues,which plays a good guiding role in improving the supply level and accessibility of generic drugs.Based on literature investigation,the typical cases of novel pharmaceutical preparations were analyzed,and the pharmaceutical considerations were put forward in terms formulation,manufacturing process and quality control,aimed to provide scientific reference for research and development of such drugs.

AIM To investigate the effects of ampelopsin-mediated autophagy and apoptosis of human cervical cancer SiHa cells.METHODS After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group,the 3-MA+ampelopsin group and the Z-VAD-FMK+ampelopsin group,the cells had their cell proliferation inhibition rate detected by MTT method.After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group and the 3-MA+ampelopsin group,the cells had their morphological changes observed under electron microscope and their apoptosis detected by Hoechst33258 and AnnexinV-FITC/PI staining.After 24 h corresponding administration and culture among the control group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group and the Z-VAD-FMK+ampelopsin group,the cells had their autophagy and ultrastructure observed by MDC method and transmission electron microscopy.After 12 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group,the 3-MA+ampelopsin group or control group,the Z-VAD-FMK (50 μmol/L) group,the ampelopsin (80 μmol/L) group,and the Z-VAD-FMK+ampelopsin group,the cells had their protein expressions of cleaved-PARP,cleaved-Caspase3,Bax,Bcl-2,Atg13,Beclin-1,LC3,and P62 detected by Western blot.RESULTS Compared with the control group,the ampelopsin group displayed enhanced proliferation inhibition of SiHa and C-33A cells (P<0.01).Compared with the ampelopsin group,the groups intervened with 3-MA+ampelopsin and Z-VAD-FMK+ampelopsin showed more significantly inhibited proliferation of the two cell lines (P<0.01),and decreased number of living cells.Compared with the ampelopsin group,the 3-MA+ampelopsin group showed increased bright blue fluorescence and apoptosis rate of SiHa cells (P<0.05),increased cleaved PARP,Bax,and P62 protein expressions (P<0.01),and decreased LC3Ⅱ/LC3Ⅰ ratio and Bcl-2 protein expression (P<0.01).Compared with the ampelopsin group,the Z-VAD-FMK+ampelopsin group demonstrated increased green dot fluorescence and number of autophagosomes and autopolysosomes,increased LC3Ⅱ/LC3Ⅰ ratio,Atg13 and Beclin-1 protein expression (P<0.05,P<0.01);and decreased protein expressions of P62,cleaved-PARP,cleaved-Caspase3 (P<0.05,P<0.01).CONCLUSION Being an antagonist of human cervical carcinoma SiHa cells,ampelopsin can induce autophagy and apoptosis of the cells through its key target on Beclin-1/Bcl-2.

AIM To investigate the effects of ampelopsin-mediated autophagy and apoptosis of human cervical cancer SiHa cells.METHODS After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group,the 3-MA+ampelopsin group and the Z-VAD-FMK+ampelopsin group,the cells had their cell proliferation inhibition rate detected by MTT method.After 24 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group and the 3-MA+ampelopsin group,the cells had their morphological changes observed under electron microscope and their apoptosis detected by Hoechst33258 and AnnexinV-FITC/PI staining.After 24 h corresponding administration and culture among the control group,the Z-VAD-FMK (50μmol/L) group,the ampelopsin (80μmol/L) group and the Z-VAD-FMK+ampelopsin group,the cells had their autophagy and ultrastructure observed by MDC method and transmission electron microscopy.After 12 h corresponding administration and culture among the control group,the 3-MA (5 mmol/L) group,the ampelopsin (80 μmol/L) group,the 3-MA+ampelopsin group or control group,the Z-VAD-FMK (50 μmol/L) group,the ampelopsin (80 μmol/L) group,and the Z-VAD-FMK+ampelopsin group,the cells had their protein expressions of cleaved-PARP,cleaved-Caspase3,Bax,Bcl-2,Atg13,Beclin-1,LC3,and P62 detected by Western blot.RESULTS Compared with the control group,the ampelopsin group displayed enhanced proliferation inhibition of SiHa and C-33A cells (P<0.01).Compared with the ampelopsin group,the groups intervened with 3-MA+ampelopsin and Z-VAD-FMK+ampelopsin showed more significantly inhibited proliferation of the two cell lines (P<0.01),and decreased number of living cells.Compared with the ampelopsin group,the 3-MA+ampelopsin group showed increased bright blue fluorescence and apoptosis rate of SiHa cells (P<0.05),increased cleaved PARP,Bax,and P62 protein expressions (P<0.01),and decreased LC3Ⅱ/LC3Ⅰ ratio and Bcl-2 protein expression (P<0.01).Compared with the ampelopsin group,the Z-VAD-FMK+ampelopsin group demonstrated increased green dot fluorescence and number of autophagosomes and autopolysosomes,increased LC3Ⅱ/LC3Ⅰ ratio,Atg13 and Beclin-1 protein expression (P<0.05,P<0.01);and decreased protein expressions of P62,cleaved-PARP,cleaved-Caspase3 (P<0.05,P<0.01).CONCLUSION Being an antagonist of human cervical carcinoma SiHa cells,ampelopsin can induce autophagy and apoptosis of the cells through its key target on Beclin-1/Bcl-2.

Objective To investigate the nutritional status of children with Crohn's Disease (CD) at diagnosis and its association with clinical characteristics. Methods A retrospective analysis was performed for the clinical data and nutritional status of 118 children with CD who were admitted to Beijing Children's Hospital,Capital Medical University,from January 2016 to January 2024. A multivariate logistic regression analysis was used to investigate the risk factors for malnutrition. Results A total of 118 children with CD were included,among whom there were 68 boys (57.6％) and 50 girls (42.4％),with a mean age of (11±4) years. Clinical symptoms mainly included recurrent abdominal pain (73.7％,87/118),diarrhea (37.3％,44/118),and hematochezia (32.2％,38/118),and 63.6％ (75/118) of the children had weight loss at diagnosis. The incidence rate of malnutrition was 63.6％ (75/118),and the children with moderate or severe malnutrition accounted for 67％ (50/75). There were 50 children (42.4％) with emaciation,8 (6.8％) with growth retardation,and 9 (7.6％) with overweight or obesity. Measurement of nutritional indices showed a reduction in serum albumin in 83 children (70.3％),anemia in 74 children (62.7％),and a reduction in 25 hydroxyvitamin D in 15 children (60％,15/25). The children with malnutrition had significantly higher disease activity,proportion of children with intestinal stenosis,and erythrocyte sedimentation rate and a significant reduction in serum albumin (P<0.05). The multivariate logistic regression analysis showed that intestinal stenosis was an independent risk factor for malnutrition in children with CD (OR=4.416,P<0.05). Conclusions There is a high incidence rate of malnutrition in children with CD at diagnosis,which is associated with disease activity and disease behavior. The nutritional status of children with CD should be closely monitored.

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.
Child ; Female ; Male ; Humans ; Retrospective Studies ; Cytokine Release Syndrome ; COVID-19/complications* ; SARS-CoV-2 ; Brain Diseases/etiology* ; Prognosis ; Seizures ; Cytokines

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness