Objective:To compare the efficacy of linaclotide and procalcitide in the treatment of adult constipation IBS-C.Methods:A retrospective study was conducted on 80 IBS-C patients admitted from May 2021 to May 2024.All patients were treated with novel secretagogues,and were divided into four groups according to the different treatment methods:linarotinib group and Pucanapide group,with 40 patients in each group.The clinical efficacy of oral administration of 290 μg of Nallotide capsules and 3 mg of Pucanapeptide in the Linalotide group and Pucanapeptide group was compared after one month of continuous treatment.The scores of IBS-C symptoms related to stool frequency,stool characteristics,upper abdominal pain,early satiety,and bloating were evaluated before and Post-treatment.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of vasoactive intestinal peptide(VIP),substance P(SP),5-hydroxytryptamine(5-HT),motilin,and gastrin IBS-C related serum markers in feces.The 16s rDNA fluorescence quantitative polymerase chain reaction method was used to detect Escherichia coli and lactate in feces.Compare the incidence of adverse reactions between the two groups based on the levels of Bacillus and Bifidobacterium.Results:There was no difference in the total effective rate between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the fecal frequency scores of the linaclotide group and the procalcitonin group were higher than pretherapy,while the fecal characteristics,upper abdominal pain,early satiety,and fullness scores were lower than pretherapy(P＜0.05).There was no difference in the fecal frequency,fecal characteristics,early satiety,and fullness scores between the linaclotide group and the procalcitonin group(P＞0.05),and the upper abdominal pain score of the linaclotide group was lower than that of the procalcitonin group(P＜0.05);Post-treatment,VIP,SP,5-HT,motilin and gastrin levels in linagliptin group and Pucanotide group were all lower than that pretherapy(P＜0.05),and there was no significant difference between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the levels of Escherichia coli in the linaclotide group and the procaine group were lower than pretherapy,while the numbers of Lactobacilli and Bifidobacteria were higher than pretherapy(P＜0.05).There was no difference between the linaclotide group and the procaine group(P＞0.05);There was no difference in the incidence of headache,bloating/abdominal pain between the linaclotide group and the procaine group(P＞0.05),and the incidence of diarrhea in the procaine group was lower than that in the linaclotide group(P＜0.05).Conclusion:Linalotide and Pucanatide have similar therapeutic effects in treating adult IBS-C,both of which can improve patients' clinical symptoms,serum biomarker levels,and intestinal microbiota structure.However,Linalotide has a better effect on improving abdominal pain,while Pucanatide can reduce the risk of diarrhea.Therefore,the clinical application of different new secretagogue drugs can be determined based on individualized symptoms and diarrhea risk of patients.

Objective To investigate the value of the combined detection of neutrophil CD64(nCD64),C-reactive protein(CRP)and lactate dehydrogenase(LDH)in the diagnosis of refractory Mycoplasma pneumoniae pneumonia(RMPP)in children.Methods A total of 147 children with Mycoplasma pneumoniae infection were enrolled and divided into the RMPP group(n=70)and the general Mycoplasma pneumoniae pneumonia group(GMPP,n=77)based on disease severity and treatment response.The age,gender,white blood cell count(WBC)within 24 hours of admission,serum procalcitonin(PCT),C-reactive protein(CRP)and lactate dehydrogenase(LDH)levels were collected in the study participants.The expression level of nCD64 in peripheral blood was measured using flow cytometry.Multivariate Logistic regression analysis was conducted to identify the independent risk factors associated with RMPP in children.Additionally,a receiver operating characteristic(ROC)curve was constructed to assess the diagnostic performance of the combined detection of nCD64,CRP and LDH for RMPP in children.Results The RMPP group had a longer hospital stay than the GMPP group(P＜0.05).Levels of nCD64,CRP and LDH were significantly higher in the RMPP group compared to those of the GMPP group(P＜0.05),and there were no significant differences in WBC and PCT levels between the two groups.Multivariate Logistic regression analysis showed that elevated nCD64,CRP and LDH were risk factors for RMPP in children(P＜0.05).ROC curve analysis revealed that the areas under the curve(AUC)for nCD64,CRP and LDH in diagnosing RMPP were 0.817,0.863 and 0.805,respectively.The combined detection of three indicators for AUC was 0.948.Conclusion The levels of nCD64,CRP and LDH in blood of children with RMPP are higher than those of children with GMPP.The combined detection of the three indicators has a high diagnostic value for RMPP in children with Mycoplasma pneumoniae pneumonia.

Objective To investigate the value of the combined detection of neutrophil CD64(nCD64),C-reactive protein(CRP)and lactate dehydrogenase(LDH)in the diagnosis of refractory Mycoplasma pneumoniae pneumonia(RMPP)in children.Methods A total of 147 children with Mycoplasma pneumoniae infection were enrolled and divided into the RMPP group(n=70)and the general Mycoplasma pneumoniae pneumonia group(GMPP,n=77)based on disease severity and treatment response.The age,gender,white blood cell count(WBC)within 24 hours of admission,serum procalcitonin(PCT),C-reactive protein(CRP)and lactate dehydrogenase(LDH)levels were collected in the study participants.The expression level of nCD64 in peripheral blood was measured using flow cytometry.Multivariate Logistic regression analysis was conducted to identify the independent risk factors associated with RMPP in children.Additionally,a receiver operating characteristic(ROC)curve was constructed to assess the diagnostic performance of the combined detection of nCD64,CRP and LDH for RMPP in children.Results The RMPP group had a longer hospital stay than the GMPP group(P＜0.05).Levels of nCD64,CRP and LDH were significantly higher in the RMPP group compared to those of the GMPP group(P＜0.05),and there were no significant differences in WBC and PCT levels between the two groups.Multivariate Logistic regression analysis showed that elevated nCD64,CRP and LDH were risk factors for RMPP in children(P＜0.05).ROC curve analysis revealed that the areas under the curve(AUC)for nCD64,CRP and LDH in diagnosing RMPP were 0.817,0.863 and 0.805,respectively.The combined detection of three indicators for AUC was 0.948.Conclusion The levels of nCD64,CRP and LDH in blood of children with RMPP are higher than those of children with GMPP.The combined detection of the three indicators has a high diagnostic value for RMPP in children with Mycoplasma pneumoniae pneumonia.

Objective:To compare the efficacy of linaclotide and procalcitide in the treatment of adult constipation IBS-C.Methods:A retrospective study was conducted on 80 IBS-C patients admitted from May 2021 to May 2024.All patients were treated with novel secretagogues,and were divided into four groups according to the different treatment methods:linarotinib group and Pucanapide group,with 40 patients in each group.The clinical efficacy of oral administration of 290 μg of Nallotide capsules and 3 mg of Pucanapeptide in the Linalotide group and Pucanapeptide group was compared after one month of continuous treatment.The scores of IBS-C symptoms related to stool frequency,stool characteristics,upper abdominal pain,early satiety,and bloating were evaluated before and Post-treatment.Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of vasoactive intestinal peptide(VIP),substance P(SP),5-hydroxytryptamine(5-HT),motilin,and gastrin IBS-C related serum markers in feces.The 16s rDNA fluorescence quantitative polymerase chain reaction method was used to detect Escherichia coli and lactate in feces.Compare the incidence of adverse reactions between the two groups based on the levels of Bacillus and Bifidobacterium.Results:There was no difference in the total effective rate between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the fecal frequency scores of the linaclotide group and the procalcitonin group were higher than pretherapy,while the fecal characteristics,upper abdominal pain,early satiety,and fullness scores were lower than pretherapy(P＜0.05).There was no difference in the fecal frequency,fecal characteristics,early satiety,and fullness scores between the linaclotide group and the procalcitonin group(P＞0.05),and the upper abdominal pain score of the linaclotide group was lower than that of the procalcitonin group(P＜0.05);Post-treatment,VIP,SP,5-HT,motilin and gastrin levels in linagliptin group and Pucanotide group were all lower than that pretherapy(P＜0.05),and there was no significant difference between linagliptin group and Pucanotide group(P＞0.05);Post-treatment,the levels of Escherichia coli in the linaclotide group and the procaine group were lower than pretherapy,while the numbers of Lactobacilli and Bifidobacteria were higher than pretherapy(P＜0.05).There was no difference between the linaclotide group and the procaine group(P＞0.05);There was no difference in the incidence of headache,bloating/abdominal pain between the linaclotide group and the procaine group(P＞0.05),and the incidence of diarrhea in the procaine group was lower than that in the linaclotide group(P＜0.05).Conclusion:Linalotide and Pucanatide have similar therapeutic effects in treating adult IBS-C,both of which can improve patients' clinical symptoms,serum biomarker levels,and intestinal microbiota structure.However,Linalotide has a better effect on improving abdominal pain,while Pucanatide can reduce the risk of diarrhea.Therefore,the clinical application of different new secretagogue drugs can be determined based on individualized symptoms and diarrhea risk of patients.

Objective To investigate the clinical efficacy of Xuanfei Yipi Formula,a prescription derived from modified Jianpi Pill recorded in Yi Fang Ji Jie(A Collection of Prescriptions with Expositions),in treating senile sarcopenia with spleen-stomach weakness type,and to observe its effect on chronic low-grade inflammation of the patients.Methods Seventy cases of senile sarcopenia patients of spleen-stomach weakness type were randomly divided into an observation group and a control group,with 35 cases in each group.The control group was given exercise and nutritional guidance,while the observation group was treated with Xuanfei Yipi Formula orally on the basis of the control group,and the intervention time of both groups was eight weeks.The changes of traditional Chinese medicine(TCM)syndrome scores,appendicular skeletal muscle mass index(ASMI),grip strength,6-meter walking pace,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6),tumor necrosis factor α(TNF-α)in the two groups before and after treatment were observed.After treatment,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After eight weeks of treatment,the total effective rate in the observation group was 94.29%(33/35),and that in the control group was 77.14%(27/35),the intergroup comparison(by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly lower than those before treatment(P＜0.05),and the decrease of TCM syndrome score in the observation group was more obviously than that in the control group(P＜0.01).(3)After eight weeks of treatment,the ASMI,grip strength and 6-meter walking pace in the two groups were significantly higher than those before treatment,and the increase of ASMI and grip strength in the observation group was more obviously than that in the control group(P＜0.05).(4)After eight weeks of treatment,the levels of serum CRP,IL-6,and TNF-α in the two groups were decreased significantly compared with those before treatment(P＜0.05),and the decrease of serum CRP level in the observation group was more obviously than that in the control group(P＜0.05).(5)During the treatment,no obvious adverse reactions occurred in both groups,and the safety indexes of liver and kidney functions of the patients were all within the normal range.Conclusion Xuanfei Yipi Formula can improve the clinical symptoms of senile sarcopenia patients,and its mechanism is probably related with the regulation of chronic low-grade inflammation.

Physiologically based pharmacokinetic (PBPK) models have been widely used to predict various stages of drug absorption, distribution, metabolism and excretion. Models based on machine learning (ML) and artificial intelligence (AI) can provide better ideas for the construction of PBPK models, which can accelerate the prediction speed and improve the prediction quality of PBPK. ML and AL can complement the advantages of PBPK model to accelerate the progress of drug research and development. This review introduces the application of machine learning and artificial intelligence in pharmacokinetics, summarizes the research progress of physiological pharmacokinetic models based on machine learning and artificial intelligence, and analyzes the limitations of machine learning and artificial intelligence applications and their application prospects and prospects.

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.
Animals ; Mice ; HMGB1 Protein ; Melatonin/therapeutic use* ; Mice, Inbred C57BL ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxygen/adverse effects* ; Peroxidase ; Receptors, Melatonin ; Retinal Diseases/drug therapy*

AIM: To investigate the effect of 3-bro-mopyruvate cholesterol ester (3-BP-Cl) on the sensitivity of breast cancer to tamoxifen (TAM). METHODS: MTT assay and Calcein AM/PI staining were used to detect the effect of drugs on the viability of breast cancer cells. Kim's formula was used to detect synergistic anti-breast cancer effect of cholesterol 3-bromopyruvate and tamoxifen. The inhibitory effect of drugs on proliferation of breast cancer cells was detected by colony-forming assay. Flow cytometry was used to detect the apoptosis of breast cancer cells. Western blot assay was used to detect the expression of hexokinase 2, Bcl-2 and Bax proteins. RESULTS: MTT results showed that combination 3-BP-Cl and TAM could significantly inhibit the activity of MCF-7 cells (P<0.05). The results of King's formula showed that 3-BP-Cl and TAM had synergistic inhibitory effect on the proliferation of MCF-7 cells (q>1.15). Calcein AM / PI staining showed that the number of dead cells was the highest in the combination group. Colony-forming assay showed that the combination group had stronger inhibitory effect on the proliferation of MCF-7 cells than that of single drug groups. AnnexinV flow cytometry results showed that, the cell apoptosis in the combination group was significantly increased (P<0.01). Western blot results showed that 3-BP-Cl inhibited the expressions of hexoktokinase 2 and Bcl-2, and enhanced the expression of Bax in MCF-7 cells. CONCLUSION: 3-BP-Cl could increase the sensitivity of breast cancer cells to tamoxifen, and synergically inhibit the proliferation of breast cancer cells. The mechanism is possibly related to its effects of inhibiting the expression of HK2/Bcl-2, and enhancing the expression of Bax.

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.