Objective To analyze the clinical characteristics and treatment strategies for Nocardia brasiliensis infection.Methods A clinical pharmacist participated in the clinical diagnosis and treatment plan for a case of a membranous nephropa-thy patient infected with Nocardia brasiliensis,resulting in multiple infections in the lungs,eyes,and nervous system.They were involved in assessing the patient's infection symptoms and severity,as well as reviewing the literature to participate in developing and optimizing the clinical drug therapy regimen.Results Following infection with Nocardia brasiliensis,the patient developed lung,eye,and nervous system infections.The patient showed significant improvement after targeted treatment by clinical doctors and clinical pharmacists.At the 3-month outpatient follow-up,the patient's lung,eye,and lower limb nervous system had re-turned to normal.Conclusions Nocardia brasiliensis can colonize in various environments,and immunocompromised individu-als are at risk of infection.Clinical diagnosis relies on metagenomic sequencing methods for identification.For mild to moderate in-fections,a combination of sulfamethoxazole/trimethoprim(TMP-SMX)can be used as monotherapy.Severe infections often re-quire a combination of two or three antibiotic drugs(such as TMP-SMX,imipenem cilastatin,amikacin)for intravenous treatment for 3-6 weeks,and followed by oral therapy.The entire course of treatment typically lasts 3-6 months.Patients with timely and ef-fective treatment usually have a better prognosis.

BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

Objective To analyze the clinical characteristics and treatment strategies for Nocardia brasiliensis infection.Methods A clinical pharmacist participated in the clinical diagnosis and treatment plan for a case of a membranous nephropa-thy patient infected with Nocardia brasiliensis,resulting in multiple infections in the lungs,eyes,and nervous system.They were involved in assessing the patient's infection symptoms and severity,as well as reviewing the literature to participate in developing and optimizing the clinical drug therapy regimen.Results Following infection with Nocardia brasiliensis,the patient developed lung,eye,and nervous system infections.The patient showed significant improvement after targeted treatment by clinical doctors and clinical pharmacists.At the 3-month outpatient follow-up,the patient's lung,eye,and lower limb nervous system had re-turned to normal.Conclusions Nocardia brasiliensis can colonize in various environments,and immunocompromised individu-als are at risk of infection.Clinical diagnosis relies on metagenomic sequencing methods for identification.For mild to moderate in-fections,a combination of sulfamethoxazole/trimethoprim(TMP-SMX)can be used as monotherapy.Severe infections often re-quire a combination of two or three antibiotic drugs(such as TMP-SMX,imipenem cilastatin,amikacin)for intravenous treatment for 3-6 weeks,and followed by oral therapy.The entire course of treatment typically lasts 3-6 months.Patients with timely and ef-fective treatment usually have a better prognosis.

BACKGROUND:Previous studies by the research group have shown that core proteoglycan in Cornus Cervi Col la can enter the bone,promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells,and has a good repair effect on steroid-induced osteonecrosis of the femoral head.OBJECTIVE:To investigate the therapeutic effect and potential mechanism of Cornus Cervi Colla on steroid-induced osteonecrosis of the femoral head in rats by fecal non-targeted fecal metabolomics.METHODS:Thirty SD rats were randomly divided into three groups using a random number table method:the control group(n=10)was injected with normal saline into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks),and was given pure water gavage(once a day for 6 consecutive weeks).The model group(n=10)was injected with methylprednisolone sodium succinate into the right gluteal muscle(injected on the first 3 days of each week for 3 consecutive weeks)to establish a steroid-induced osteonecrosis of the femoral head model,and was given pure water gavage(once a day for 6 consecutive weeks).The Cornus Cervi Co I la group(n=10)was also established with a steroid-induced osteonecrosis of the femoral head model,and was given Cornus Cervi Col la gavage(once a day for 6 consecutive weeks).After gavage,cecal feces and femoral heads were collected for fecal metabolomics analysis and bone tissue Micro-CT and hematoxylin-eosin staining,respectively.RESULTS AND CONCLUSION:(1)Metabolomics analysis results showed that there were 233 differential metabolites between the Cornus Cervi Col la and model groups,with 65 significantly differing and clearly annotated metabolites.Lipid and amino acid metabolites were significantly increased,with bile acids,sulfated steroids,ephedrine,hypoxanthine,betaine,L-carnitine,B-mouse bile acid,cytidine,4-pyridoxic acid,taurine,N-acetyl-d-glucosamine,and butyric acid being the most impacted(variable weight value VIP＞5).The metabolic pathways of taurine and hypotaurine were crucial in the metabolic regulatory network(pathway impact=0.428 57).(2)Micro-CT scanning results of bone tissue showed that the femoral heads of rats in the model group and the Cornus Cervi Col la group had different degrees of damage;the femoral head contour was irregular;the trabeculae in the subchondral bone of the femoral head were missing and disordered,and some cystic structures were visible.Compared with the model group,the degree of trabecular damage in the rats of the Cornus Cervi Colla group was milder.Hematoxylin-eosin staining results showed that the trabeculae in the subchondral bone of the femoral heads of rats in the model group and the Cornus Cervi Colla group were sparse or interrupted,and the empty bone lacuna rate and adipocyte invasion were increased.Compared with the model group,the empty bone lacuna rate and adipocyte invasion in the subchondral bone of the femoral heads of rats in the Cornus Cervi Colla group were reduced.(3)These results conclude that Cornus Cervi Colla potentially mitigates steroid-induced osteonecrosis of the femoral head through the metabolic processes involving taurine and associated pathways.

Objective In this study,we analyzed the transcriptome sequences of Kupffer cells exposed to simulated microgravity for 3 d and conducted biological experiments to determine how microgravity initiates apoptosis in Kupffer cells. Methods Rotary cell culture system was used to construct a simulated microgravity model.GO and KEGG analyses were conducted using the DAVID database.GSEA was performed using the R language.The STRING database was used to conduct PPI analysis.qPCR was used to measure the IL1B,TNFA,CASP3,CASP9,and BCL2L11 mRNA expressions.Western Blotting was performed to detect the level of proteins CASP3 and CASP 9.Flow cytometry was used to detect apoptosis and mitochondrial membrane cells.Transmission electron microscopy was used to detect changes in the ultrastructure of Kupffer cells. Results Transcriptome Sequencing indicated that simulated microgravity affected apoptosis and the inflammatory state of Kupffer cells.Simulated microgravity improved the CASP3,CASP9,and BCL2L11 expressions in Kupffer cells.Annexin-V/PI and JC-1 assays showed that simulated microgravity promoted apoptosis in Kupffer cells.Simulated microgravity causes M1 polarization in Kupffer cells. Conclusion Our study found that simulated microgravity facilitated the apoptosis of Kupffer cells through the mitochondrial pathway and activated Kupffer cells into M1 polarization,which can secrete TNFA to promote apoptosis.

According to understanding of the pathogenesis of acne, scholars have established animal models of acne inflammation, animal models of grafting human skin acne, and natural acne animal models. The acne inflammation model is mainly induced by bacterial infection, chemical drug application, and foreign matter injection. Natural acne animal models include animals that some are sensitivity to hormones and some have clinical symptoms of acne. It is necessary to select appropriate model animals and replicate model methods for the development of acne intervention products with different degrees and mechanisms. At present, there are only human evaluation standards of acne health functions in China, but no animal evaluation standards, which has affected the in-depth study of the pathogenesis of acne as well as the research and development progress of acne products. This article summarizes the conditions for the occurrence of acne, the characteristics of human skin, the bidirectional effect of Cutibacterium acnes on human skin, acne animal models, and commonly used observation and evaluation indicators, providing the reference for studying the pathogenesis of acne, promoting acne treatment and health care, and developing treatment products.

Objective:To investigate the relationship between the mechanism of ulinastatin reducing perioperative myocardial injury and ferroptosis in peripheral blood mononuclear cells (PBMCs) in pediatric patients undergoing heart surgery under cardiopulmonary bypass (CPB).Methods:A total of 60 pediatric patients of either sex, aged 4-8 yr, of American Association of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective repair of ventricular septal defect under CPB, were divided into 2 groups by a random number table method: control group (C group) and ulinastatin group (UTI group), with 30 cases in each group.Combined intravenous-inhalational anesthesia was used.In UTI group, ulinastatin 20 000 U/kg was diluted to 100 ml in normal saline, 50 ml was infused through the central vein over 15 min starting from 20 min before skin incision, and the remaining 50 ml was instilled through the CPB pipeline over 15 min starting from 10 min of CPB.The equal volume of normal saline was given instead in C group.Blood samples from the internal jugular vein were collected after anesthesia induction and before skin incision (T 1), at 30 min after start of CPB (T 2), immediately after termination of CPB (T 3) and at 24 h after termination of CPB (T 4) for determination of the levels of amino-terminal B-type pro-brain natriuretic peptide (NT-proBNP), cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) in plasma by enzyme-linked immunosorbent assay.PBMCs were extracted by modified Ficoll density gradient centrifugation method for determination of the concentrations of Fe 2+ and malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in PBMCs (by colorimetric method) and expression of long-chain acyl-CoA synthase 4 (ACSL4) and glutathione peroxidase 4 (GPX4) in PBMCs (by Western blot). Results:Compared with the baseline at T 1, the levels of NT-proBNP, cTnI and CK-MB in plasma were significantly increased, the concentrations of Fe 2+ and MDA in PBMCs were increased, the expression of ACSL4 in PBMCs was up-regulated, and the activity of SOD was decreased, and the expression of GPX4 was down-regulated at T 2-4 in two groups ( P<0.05). Compared with C group, the plasma levels of NT-proBNP, cTnI and CK-MB were significantly decreased, the concentrations of Fe 2+ and MDA in PBMCs were decreased, the expression of ACSL4 in PBMCs was down-regulated, the activity of SOD was increased, and the expression of GPX4 was up-regulated at T 2-4 in UTI group ( P<0.05). Conclusion:The mechanism by which ulinastatin reduces perioperative myocardial injury may be related to inhibition of ferroptosis in PBMCs in the pediatric patients undergoing open heart surgery under CPB.

Objective:To investigate the thermal injury effects on human HaCaT cells under simulated microgravity environment.Methods:The human HaCaT cells were collected and divided into simulated microgravity thermal injury (SMGTI) group, normal gravity thermal injury (NGTI) group, and normal gravity false injury (NGFI) group according to the random number table. Cells in NGTI and NGFI groups were cultured routinely in culture bottle, and cells in SMGTI group were cultured in the rotary cell culture system to simulate microgravity environment. Cells in SMGTI and NGTI groups were bathed in hot water of 45 ℃ for 10 minutes to make thermal injury model, and cells in NGFI group were bathed in warm water of 37 ℃ for 10 minutes to simulate thermal injury. At post injury hour (PIH) 12, cell morphology of 3 groups was observed under inverted phase contrast electron microscope. At PIH 2, 6, and 12, single cell suspension in the 3 groups was collected to detect the cell cycle by flow cytometer and the mRNA expressions of heat shock protein 70 (HSP70), matrix metalloproteinase 9 (MMP-9), and cysteine-aspartic protease 3 (caspase-3) by real time fluorescence quantitative reverse transcription polymerase chain reaction, and the experiments were repeated for 3 times. At PIH 2, 6, and 12, cell culture supernatant in the 3 groups was collected to detect the concentration of heparin-binding epidermal growth factor (HB-EGF) by enzyme linked immunosorbent assay method, the experiment was repeated for 3 times. The sample in each group and each time point was 3. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, and Mann-Whitney U test. Results:(1) At PIH 12, cells in NGFI group showed regular shape and regular arrangement, with no cell debris. The cell shape in NGTI group was generally regular, with fewer cell debris and closer arrangement than that in NGFI group. The cells in SMGTI group showed more irregular shapes, different sizes, and dead cell debris. (2) The percentage of G1 phase cells in NGTI group was significantly higher than that in NGFI group and SMGTI group at PIH 2, respectively ( P<0.05), and the percentage of G1 phase cells in NGTI group was significantly lower than that in NGFI group and SMGTI group at PIH 6 and 12, respectively ( P<0.05). The percentage of G2/M phase cells in NGTI group was significantly lower than that in SMGTI group at PIH 2 ( P<0.05), and the percentage of G2/M phase cells in NGTI group was significantly higher than that in NGFI group and SMGTI group at PIH 6 and 12, respectively ( P<0.05). The percentage of S phase cells in NGTI group at PIH 2, 6, and 12 was significantly higher than that in SMGTI group ( P<0.05), and the percentage of S phase cells in NGTI group at PIH 2 and 6 was significantly lower than that in NGFI group ( P<0.05). (3) The HSP70 mRNA expressions of cells in NGTI group were 2.50±0.30 and 3.99±0.35 at PIH 2 and 6, which were significantly higher than 1.14±0.15 and 0.82±0.27 in NGFI group ( P<0.05), and 1.17±0.53 and 1.65±0.59 in SMGTI group ( P<0.05). The MMP-9 mRNA expression of cells in SMGTI group was significantly higher than that in NGTI group at PIH 2, 6, and 12, respectively ( Z=-2.319, -2.882, -2.908, P<0.05). At each time point after injury, the mRNA expression of caspase-3 of cells in NGTI group was similar to that in NGFI group and SMGTI group, respectively ( P>0.05). (4) The concentration of HB-EGF in cell culture supernatant of NGTI group was significantly lower than that in NGFI group at PIH 2, 6 and 12 ( P<0.05), and the concentration of HB-EGF in cell culture supernatant of SMGTI group was significantly higher than that in NGTI group at PIH 2 and 6 ( P<0.05). Conclusions:The proliferation and secretion functions and expression of wound repair related protein of human HaCaT cells inflicted with thermal injury in simulated microgravity environment showed complex and diversified changes, which provide theoretical basis for further research on damage repair under weightlessness.

Objective: To evaluate the role of necroptosis in hyperoxia-induced acute lung injury (ALI) in preadolescent rats. Methods: A total of 72 clean-grade healthy male Sprague-Dawley rats, aged 14 days, weighing 40-50 g, were divided into 3 groups (n=24 each) by using a random number table method: control group (group C), hyperoxia-induced ALI group (group ALI) and hyperoxia-induced ALI and necrostatin-1 group (group ALI+ N). The rats of group ALI+ N was intraperitoneally injected with necrostatin-1 1.0 mg/kg once a day for 3 consecutive days.The rats were intraperitoneally injected with dimethyl sulfoxide 0.2 ml/kg once a day for 3 consecutive days in C and ALI groups.The animals were sacrificed at 72 h after inhaling oxygen, and bronchoalveolar lavage fluid (BALF) was collected for determination of interleukin-6 (IL-6) and IL-8 concentrations (by enzyme-linked immunosorbent assay), superoxide dismutase (SOD) activity (by xanthine oxidase method), and malondialdehyde (MDA) concentration (by thiobarbituric acid method). Lung tissues were taken for measurement of wet/dry weight ratio (W/D ratio) and for examination of the pathological changes (with a light microscope) and ultrastructure of lung tissues (with an electron microscope). The injured alveolus rate (IAR) was calculated.The expression of receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed-lineage kinase domain-like protein (MLKL) in lung tissues was detected by Western blot. Results: Compared with group C, the concentrations of IL-6, IL-8 and MDA in BALF were significantly increased, the activity of SOD in BALF was decreased, the W/D ratio and IAR of lung tissues were increased, the expression of RIPK1, RIPK3 and MLKL in lung tissues was up-regulated (P<0.05), and the pathological damage was accentuated in group ALI.Compared with group ALI, the concentrations of IL-6, IL-8 and MDA in BALF were significantly deceased, the activity of SOD in BALF was increased, the W/D ratio and IAR of lung tissues were decreased, the expression of RIPK1, RIPK3 and MLKL in lung tissues was down-regulated (P<0.05), and the pathological damage was significantly attenuated in group ALI+ N. Conclusion Necroptosis is involved in the pathophysiological process of hyperoxia-induced ALI in preadolescent rats.

Objective To evaluate the role of necroptosis in hyperoxia-induced acute lung injury(ALI)in preadolescent rats.Methods A total of 72 clean-grade healthy male Sprague-Dawley rats,aged 14 days,weighing 40-50 g,were divided into 3 groups(n＝24 each)by using a random number table method: control group(group C),hyperoxia-induced ALI group(group ALI)and hyperoxia-induced ALI and necrostatin-1 group(group ALI+N).The rats of group ALI+N was intraperitoneally injected with ne-crostatin-1 1.0 mg/kg once a day for 3 consecutive days.The rats were intraperitoneally injected with dime-thyl sulfoxide 0.2 ml/kg once a day for 3 consecutive days in C and ALI groups.The animals were sacrificed at 72 h after inhaling oxygen,and bronchoalveolar lavage fluid(BALF)was collected for determination of interleukin-6(IL-6)and IL-8 concentrations(by enzyme-linked immunosorbent assay),superoxide dis-mutase(SOD)activity(by xanthine oxidase method),and malondialdehyde(MDA)concentration(by thiobarbituric acid method).Lung tissues were taken for measurement of wet/dry weight ratio(W/D ratio)and for examination of the pathological changes(with a light microscope)and ultrastructure of lung tissues(with an electron microscope).The injured alveolus rate(IAR)was calculated.The expression of recep-tor-interacting protein kinase 1(RIPK1),RIPK3 and mixed-lineage kinase domain-like protein(MLKL)in lung tissues was detected by Western blot.Results Compared with group C,the concentrations of IL-6,IL-8 and MDA in BALF were significantly increased,the activity of SOD in BALF was decreased,the W/D ratio and IAR of lung tissues were increased,the expression of RIPK1,RIPK3 and MLKL in lung tis-sues was up-regulated(P＜0.05),and the pathological damage was accentuated in group ALI.Compared with group ALI,the concentrations of IL-6,IL-8 and MDA in BALF were significantly deceased,the ac-tivity of SOD in BALF was increased,the W/D ratio and IAR of lung tissues were decreased,the expres-sion of RIPK1,RIPK3 and MLKL in lung tissues was down-regulated(P＜0.05),and the pathological damage was significantly attenuated in group ALI+N.Conclusion Necroptosis is involved in the patho-physiological process of hyperoxia-induced ALI in preadolescent rats.