Pneumocystis jirovecii pneumonia (PJP) is an opportunistic pulmonary infection that commonly occurs in immunocompromised children. We report a case of infantile leukemia complicated by PJP and review the relevant literature. A summary and analysis of 10 infantile leukemia patients with PJP infection (9 cases reported in the literature and 1 case from our center) showed that PJP mostly occurred in the early stages of chemotherapy (80%, 8/10). The main clinical manifestations were dyspnea (100%, 10/10) and hypoxemia (50%, 5/10), while pulmonary imaging findings lacked specificity. In most cases (50%, 5/10), diagnosis was established by identifying pathogens in bronchoalveolar lavage fluid under microscopy. In our case, diagnosis was confirmed using targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid. Treatment with intravenous sulfamethoxazole complex was administered in 8 patients, all of whom eventually recovered. PJP may occur in the early stages of chemotherapy for infantile leukemia, thus early prevention is necessary. tNGS facilitates early diagnosis of PJP, and sulfamethoxazole complex remains an effective therapeutic option.
Humans ; Infant ; Bronchoalveolar Lavage Fluid/microbiology* ; Immunocompromised Host ; Leukemia/complications* ; Pneumocystis carinii/isolation & purification* ; Pneumonia, Pneumocystis/diagnosis* ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use*

Objective To explore the mechanism of the modified Erchen Decoction in preventing and treating hyperlipidemia with phlegm-dampness syndrome based on network pharmacology and animal experiment.Methods Active components and potential targets of modified Erchen Decoction were screened using TCMSP database.Hyperlipidemia disease targets were retrieved from GeneCards,DrugBank,DisGeNET,OMIM and TTD databases,and the intersection of drugs and disease targets was taken.A protein-protein interaction network was constructed using STRING database,and GO and KEGG pathway enrichment analysis on intersecting targets was conducted using DAVID database.Cytoscape 3.9.1 software constructed a component-target-pathway network to analyze key pathways.The molecular docking between main active components and key targets was performed.A rat model of hyperlipidemia with phlegm dampness syndrome was prepared,and was intervened with modified Erchen Decoction.Liver index was calculated,lipid levels were detected,liver tissue morphology was observed by HE staining,and related protein expressions in liver tissue were detected by Western blot.Results Network pharmacology analysis showed that there were 41 targets of modified Erchen Decoction in preventing and treating hyperlipidemia,including HMGCR,SREBF1,FASN,etc.,involved in AMPK signaling pathway,lipid and atherosclerosis,chemical carcinogenesis-receptor activation,etc.The animal experiment results showed that modified Erchen Decoction could effectively regulate the blood lipid levels of model rats,reduce liver fat accumulation,significantly increase p-AMPK protein expression in liver tissue(P<0.05),and reduce HMGCR,SREBP1c and FAS protein expressions(P<0.05).Conclusion Modified Erchen Decoction may inhibit the synthesis and absorption of cholesterol and fatty acids by activating AMPK/SREBP1c signaling pathway,so as to improve hyperlipidemia.

Objective:To observe the efficacy and safety of adrenocorticotropic hormone (ACTH) therapy in children with steroid dependent nephrotic syndrome (SDNS)/frequently relapsed nephrotic syndrome (FRNS).Methods:The clinical data of children with SDNS/FRNS who received treatment with prednisone acetate tablets were retrospectively collected from June 2019 to June 2023 in the Nephrology Department of Xi′an Children′s Hospital. The children were divided into glucocorticoid+ACTH group and glucocorticoid group, according to whether ACTH was used or not. The differences in cortisol, total cholesterol and 24 hour urinary protein quantity between 2 groups of children at baseline and follow-up endpoints were compared, and the effectiveness (the proportion of no recurrence and discontinuation of glucocorticoid) and occurrence of adverse reactions were evaluated.Results:A total of 39 patients with SDNS/FRNS were included in this study, with 21 cases in the glucocorticoid+ACTH group and 18 cases in the glucocorticoid group. Among the 39 children, there were 33 cases of SDNS and 6 cases of FRNS, respectively. The proportion of baseline low cortisol levels was 76.9% (30/39). The proportion of cortisol levels returning to normal after ACTH treatment in the glucocorticoid+ACTH group was 76.2% (16/21). The baseline and follow-up endpoint for cortisol levels in the glucocorticoid+ACTH group were 28.0(19.8, 51.5) μg/L and 79.9(58.9, 113.0) μg/L, respectively. The baseline and follow-up endpoint for cortisol levels in the glucocorticoid group were 21.0(15.8, 37.4) μg/L and 25.3(18.2, 51.4) μg/L, respectively. In the 2 groups of cortisol levels, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=11.595, P=0.001), there was a statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=19.462, P<0.001), and the difference was statistically significant in the time effect of the glucocorticoid+ACTH group ( Wald χ2=21.100, P<0.001). The baseline and follow-up endpoint for total cholesterol in the glucocorticoid+ACTH group were 4.95(4.23, 5.26) mmol/L and 4.38(4.04, 5.24) mmol/L, respectively. The baseline and follow-up endpoint for total cholesterol in the glucocorticoid group were 4.80 (4.17, 5.28) mmol/L and 5.74 (5.04, 6.88) mmol/L, respectively. In the 2 groups of total cholesterol, there was statistically significant difference in the interaction effect between time and group ( Wald χ 2=9.842, P=0.002), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ 2=12.187, P<0.001), the difference was statistically significant between the 2 groups in the time effect at baseline and the follow-up endpoint (glucocorticoid+ACTH group: Wald χ 2=6.488, glucocorticoid group: Wald χ2=7.112; all P<0.05). The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid+ACTH group were 115 (105, 128) mg/d and 121 (113, 128) mg/d, respectively. The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid group were 118 (113, 125) mg/d and 138 (119, 2 100) mg/d, respectively. In the 2 groups of 24 hour urinary protein quantity, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=7.743, P=0.005), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=7.779, P=0.005), and the difference was statistically significant in the time effect of the glucocorticoid group ( Wald χ2=13.331, P<0.001). The proportion of no recurrence (17/21) and discontinuation of oral glucocorticoid (16/21) in the glucocorticoid+ACTH group were higher than those in the glucocorticoid group (the proportion were both 6/18), and the differences between the 2 groups were statistically significant (the chi square values were 9.084 and 7.240, respectively; all P<0.01). No adverse reactions occurred in the glucocorticoid group. The incidence of adverse reactions in the glucocorticoid+ACTH group was 14.3% (3/21), of which 2 cases developed generalized urticaria and 1 case developed hypertension. Conclusions:ACTH has a good efficacy and safety in children with SDNS/FRNS. The results of this study need to be further validated by increasing the sample size and conducting multicenter studies.

Objective To explore the mechanism of the modified Erchen Decoction in preventing and treating hyperlipidemia with phlegm-dampness syndrome based on network pharmacology and animal experiment.Methods Active components and potential targets of modified Erchen Decoction were screened using TCMSP database.Hyperlipidemia disease targets were retrieved from GeneCards,DrugBank,DisGeNET,OMIM and TTD databases,and the intersection of drugs and disease targets was taken.A protein-protein interaction network was constructed using STRING database,and GO and KEGG pathway enrichment analysis on intersecting targets was conducted using DAVID database.Cytoscape 3.9.1 software constructed a component-target-pathway network to analyze key pathways.The molecular docking between main active components and key targets was performed.A rat model of hyperlipidemia with phlegm dampness syndrome was prepared,and was intervened with modified Erchen Decoction.Liver index was calculated,lipid levels were detected,liver tissue morphology was observed by HE staining,and related protein expressions in liver tissue were detected by Western blot.Results Network pharmacology analysis showed that there were 41 targets of modified Erchen Decoction in preventing and treating hyperlipidemia,including HMGCR,SREBF1,FASN,etc.,involved in AMPK signaling pathway,lipid and atherosclerosis,chemical carcinogenesis-receptor activation,etc.The animal experiment results showed that modified Erchen Decoction could effectively regulate the blood lipid levels of model rats,reduce liver fat accumulation,significantly increase p-AMPK protein expression in liver tissue(P<0.05),and reduce HMGCR,SREBP1c and FAS protein expressions(P<0.05).Conclusion Modified Erchen Decoction may inhibit the synthesis and absorption of cholesterol and fatty acids by activating AMPK/SREBP1c signaling pathway,so as to improve hyperlipidemia.

Objective:To observe the efficacy and safety of adrenocorticotropic hormone (ACTH) therapy in children with steroid dependent nephrotic syndrome (SDNS)/frequently relapsed nephrotic syndrome (FRNS).Methods:The clinical data of children with SDNS/FRNS who received treatment with prednisone acetate tablets were retrospectively collected from June 2019 to June 2023 in the Nephrology Department of Xi′an Children′s Hospital. The children were divided into glucocorticoid+ACTH group and glucocorticoid group, according to whether ACTH was used or not. The differences in cortisol, total cholesterol and 24 hour urinary protein quantity between 2 groups of children at baseline and follow-up endpoints were compared, and the effectiveness (the proportion of no recurrence and discontinuation of glucocorticoid) and occurrence of adverse reactions were evaluated.Results:A total of 39 patients with SDNS/FRNS were included in this study, with 21 cases in the glucocorticoid+ACTH group and 18 cases in the glucocorticoid group. Among the 39 children, there were 33 cases of SDNS and 6 cases of FRNS, respectively. The proportion of baseline low cortisol levels was 76.9% (30/39). The proportion of cortisol levels returning to normal after ACTH treatment in the glucocorticoid+ACTH group was 76.2% (16/21). The baseline and follow-up endpoint for cortisol levels in the glucocorticoid+ACTH group were 28.0(19.8, 51.5) μg/L and 79.9(58.9, 113.0) μg/L, respectively. The baseline and follow-up endpoint for cortisol levels in the glucocorticoid group were 21.0(15.8, 37.4) μg/L and 25.3(18.2, 51.4) μg/L, respectively. In the 2 groups of cortisol levels, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=11.595, P=0.001), there was a statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=19.462, P<0.001), and the difference was statistically significant in the time effect of the glucocorticoid+ACTH group ( Wald χ2=21.100, P<0.001). The baseline and follow-up endpoint for total cholesterol in the glucocorticoid+ACTH group were 4.95(4.23, 5.26) mmol/L and 4.38(4.04, 5.24) mmol/L, respectively. The baseline and follow-up endpoint for total cholesterol in the glucocorticoid group were 4.80 (4.17, 5.28) mmol/L and 5.74 (5.04, 6.88) mmol/L, respectively. In the 2 groups of total cholesterol, there was statistically significant difference in the interaction effect between time and group ( Wald χ 2=9.842, P=0.002), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ 2=12.187, P<0.001), the difference was statistically significant between the 2 groups in the time effect at baseline and the follow-up endpoint (glucocorticoid+ACTH group: Wald χ 2=6.488, glucocorticoid group: Wald χ2=7.112; all P<0.05). The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid+ACTH group were 115 (105, 128) mg/d and 121 (113, 128) mg/d, respectively. The baseline and follow-up endpoint for 24 hour urinary protein quantity in the glucocorticoid group were 118 (113, 125) mg/d and 138 (119, 2 100) mg/d, respectively. In the 2 groups of 24 hour urinary protein quantity, there was statistically significant difference in the interaction effect between time and group ( Wald χ2=7.743, P=0.005), there was statistically significant difference at the follow-up endpoint between the 2 groups ( Wald χ2=7.779, P=0.005), and the difference was statistically significant in the time effect of the glucocorticoid group ( Wald χ2=13.331, P<0.001). The proportion of no recurrence (17/21) and discontinuation of oral glucocorticoid (16/21) in the glucocorticoid+ACTH group were higher than those in the glucocorticoid group (the proportion were both 6/18), and the differences between the 2 groups were statistically significant (the chi square values were 9.084 and 7.240, respectively; all P<0.01). No adverse reactions occurred in the glucocorticoid group. The incidence of adverse reactions in the glucocorticoid+ACTH group was 14.3% (3/21), of which 2 cases developed generalized urticaria and 1 case developed hypertension. Conclusions:ACTH has a good efficacy and safety in children with SDNS/FRNS. The results of this study need to be further validated by increasing the sample size and conducting multicenter studies.

Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway regulates multiple processes in neurons,including growth,development,proliferation and differentiation,and is closely associated with the onset,progression and treatment of cerebral ischemia-reperfusion injury(CIRI).This article provides an overview of the JAK2/STAT3 signaling pathway and its relationship with CIRI,followed by a comprehensive review of the current research status on the regulation of the JAK2/STAT3 signaling pathway by traditional Chinese medicine(TCM)to ameliorate CIRI.Among them,TCM monomers and compound prescriptions such as glycyrrhetinic acid,triptolide,and Taohong siwu decoction can inhibit inflammatory responses,enhance cellular autophagy,and suppress apoptosis by inhibiting the JAK2/STAT3 signaling pathway,thereby alleviating CIRI.In addition,TCM monomers and compound prescriptions like astragaloside Ⅳ,ginkgolide K,and Qingnao dripping pills can mitigate CIRI by activating the JAK2/STAT3 signaling pathway to inhibit oxidative stress,promote angiogenesis,and enhance neuronal survival rates.

BACKGROUND:Endothelial injury is one of the causes of cardiovascular diseases.Human induced pluripotent stem cells are easy to obtain,have strong differentiation ability,and have less exclusiveness,and their endothelial differentiated cells can be used as ideal cells for cardiovascular disease research. OBJECTIVE:To investigate the effect and mechanism of calycosin on endothelial differentiation of human induced pluripotent stem cells and to provide technical support for microvascular regeneration. METHODS:Human induced pluripotent stem cells were divided into control group and calycosin group(1.25,2.5 μg/mL),and growth factors were added to induce single-layer endothelial differentiation.After the induction of differentiation for 8 days,the positive rate of endothelial cell marker CD144 was detected by flow cytometry.Fluorescent expressions of CD144 and CD31 were detected by the immunofluorescence method.Lentivirus RNAi GFP puromycin was used to silence human-induced pluripotent stem cell Piezo1 mRNA followed by endothelial directed differentiation.After 8 days of differentiation,the positive rate of CD144 in differentiated cells was detected by flow cytometry.The mRNA expression levels of CD144,Piezo1 and MEK were detected by qPCR. RESULTS AND CONCLUSION:(1)Compared with the control group,the positive rate of CD144 was significantly increased in the 1.25 and 2.5 μg/mL calycosin groups(P<0.05).The expressions of CD144,Piezo1,and MEK mRNA were increased in the 2.5 μg/mL calycosin group(P<0.05).The fluorescence expressions of CD144(P<0.01)and CD31(P<0.001)were significantly increased in the 2.5 μg/mL calycosin group.(2)Compared with the shNT group,CD144 positive rate and CD144,Piezo1,MEK mRNA expressions were significantly increased in the shNT + calycosin 1.25,2.5 μg/mL groups(P<0.05).Compared with the shPiezo1 group,the positive rate of CD144 and mRNA expressions of CD144,Piezo1 and MEK had no significant changes in the shPiezo1+calycosin 1.25,2.5 μg/mL groups(P>0.05).(3)It is concluded that 2.5 μg/mL calycosin promotes the differentiation of human-induced pluripotent stem cells into endothelial lineages.Calycosin promotes the downstream MEK expression,thereby promoting the endothelial differentiation of human induced pluripotent stem cells by targeting the expression level of Piezo1.

Objective:To explore the efficacy of online pulmonary rehabilitation (PR) management among community-dwelling patients with stable chronic obstructive pulmonary disease (COPD).Methods:This study was a single-center randomized controlled trail with an unblinded design. A total of 130 patients with stable COPD who visited Zhuanqiao Community Health Service Center in Shanghai Minhang District from October 2020 to March 2022 were randomly divided into study group and control group with 65 cases in each group. Both groups received conventional treatment, while patients in study group attended online rehabilitation management, including face-to-face rehabilitation instruction and multiple online guidance. Pulmonary ventilation function including forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1) and percentage of forced expiratory volume in the first second to forced expiratoty volume (FEV 1%pred), modified British Medical Research Council Dyspnea Scale (mMRC), chronic obstructive pulmonary disease assessment test (CAT), score of 6 minutes walking distance (6MWD) and DOSE (dyspnea, degree of airflow obstruction, smoking status, the number of exacerbation) index were measured at baseline and after 8 weeks of rehabilitation, and compared between two groups. Results:The baseline data of the two groups were comparable. After 8 weeks of management, FVC, FEV 1, FEV 1%pred, mMRC, CAT, 6MWD and DOSE index of both groups were improved compared with the baseline level(control group: t=-7.799, -7.581, -9.010, 3.565, 9.887, -16.677, 3.795; study group: t=-12.623, -13.914, -17.644, 7.404, 22.457, -26.826, 7.968; all P<0.05). The FEV 1%pred, CAT and 6MWD in the study group were better than those in the control group ( t=-2.939, 2.277,-2.130, all P<0.05); while there were no significant differences in FVC, FEV 1, mMRC and DOSE index between the two groups( t=-0.162, -1.280, 0.925, 1.939,all P>0.05). Conclusions:The online pulmonary rehabilitation management can better improve lung function, dyspnea symptoms and exercise tolerance of patients with stable COPD, which can be used for rehabilitation training and management of community-dwelling patients.

AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.

Objective:To compare the short-term efficacy of drug-coated balloon and common balloon in the treatment of with below-the-ankle arteriosclerosis obliterans (ASO).Methods:The clinical and follow-up data of 115 patients (118 limbs) with lower extremity ASO of Rutherford 4-6 admitted to the Department of Peripheral Vascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences from Jun 2021 to Jun 2023 were retrospectively analyzed.Results:Patients were divided into group of 52 limbs using paclitaxel-coated balloon and group of 66 limbs using common balloon. During the 6-month follow-up period, The total effective rate of wound surface was 98.1% in the drug-coated balloon group and 92.4% in the common balloon group. The difference was statistically significant ( P<0.05); the increase of ankle-brachial index (ABI) and toe-brachial index (TBI) in the drug-coated balloon group were significantly better than common balloon group, and the difference was statistically significant ( P<0.01). No major adverse events occurred in the two groups during the 6-month follow-up period. Compared with the common balloon group, the drug-coated balloon group had a higher limb salvage rate (100.0% vs. 98.5% ) and a lower target vessel reconstruction rate (7.7% vs.18.2%), though the difference was not statistically significant ( P>0.05). Conclusion:Compared with the common balloon, the drug-coated balloon is more effective in the treatment of patients with wound healing rate and vascular patency rate in Rutherford 4-6 grade below-the-ankle artery lesions.