ObjectiveTo explore the mechanism of Qidi Tangshen prescription （QDTS） in alleviating podocyte injury and reducing urinary protein in diabetic nephropathy （DN）. MethodUsing network pharmacology methods， we collected the chemical components and targets of QDTS， as well as the targets related to DN. Subsequently， we constructed a "drug-ingredient-target-disease" network for QDTS in the treatment of DN to systematically elucidate the mechanism. The db/db mice were assigned into the model， QDTS （3.34 g·kg^-1）， and losartan capsules （10.29 mg·kg^-1） groups， and db/m mice served as the normal group. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and the urinary albumin excretion rate （UAER） and renal pathological changes were measured and observed. The expression levels of protein kinase B1 （Akt1）， hypoxia-inducible factor-1 alpha （HIF-1α）， phosphorylated B-cell lymphoma-extra-large （p-Bcl-xl）， as well as autophagy-related indicators microtubule-associated protein 1 light chain 3 （LC3）， ubiquitin-binding protein p62 （p62）， and autophagy-related gene 6 homolog （Beclin1）， were determined. Furthermore， mouse podocytes were divided into the normal glucose （5.5 mmol·L^-1）， high glucose （35 mmol·L^-1）， DMSO （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder） groups. After 48 h of intervention， the protein levels of Akt1， HIF-1α， p-Bcl-xl， LC3， p62， and Beclin1 in podocytes were measured. ResultQDTS had 34 active components acting on 143 targets in the treatment of DN， and 55 targets were related to autophagy， in which Akt1， HIF-1α， and Bcl-xl were the key targets. Compared with the normal group， mice in the model group exhibited significantly increased UAER， glomerular hypertrophy， deposition of blue collagen fibers， thickening of the glomerular basement membrane， and noticeable fusion of podocyte foot processes in some segments. Furthermore， the modeling up-regulated the protein levels of p-Akt1， HIF-1α， and p62 and down-regulating the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. Compared with the model group， QDTS and losartan decreased UAER （P<0.05） and alleviated the pathological damage in the renal tissue. Moreover， QDTS and losartan down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in the renal tissue （P<0.05）. In comparison to the normal glucose group， the high glucose group displayed up-regulated protein levels of p-Akt1， HIF-1α， and p62 and down-regulated protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. Compared with the high glucose group， QDTS down-regulated the protein levels of p-Akt1， HIF-1α， and p62 and up-regulated the protein levels of p-Bcl-xl， LC3， and Beclin1 in podocytes （P<0.05）. ConclusionQDTS alleviates podocyte damage and reduced urinary protein in DN by regulating the Akt1/HIF-1α/Bcl-xl signaling pathway， thereby enhancing podocyte autophagy.

ObjectiveTo explore the molecular mechanism of Qidi Tangshen prescription （QDTS） in regulating podocyte pyroptosis in diabetes nephropathy （DN）. MethodThrough in vivo experiment， db/db mice were divided into the model group， QDTS group （3.34 g·kg^-1）， valsartan capsule group （10.29 mg·kg^-1）， with db/m mice serving as the normal control. Each group consisted of 8 mice， and they underwent continuous intervention for 8 weeks. After the last administration， mice were euthanized， and kidney pathological changes were observed. Additionally， the expression levels of pyroptosis-related indicators， including NOD-like receptor protein 3 （NLRP3）， Gasdermin D protein （GSDMD）， and interleukin-1β （IL-1β） protein， were examined. Through in vitro experiment， mouse podocytes were divided into the normal glucose group （5.5 mmol·L^-1 glucose）， high glucose group （35 mmol·L^-1 glucose）， DMSO group （35 mmol·L^-1 glucose+200 mg·L^-1 DMSO）， and QDTS group （35 mmol·L^-1 glucose+200 mg·L^-1 QDTS freeze-dried powder）. After 48 hours of intervention， the expression levels of NLRP3， GSDMD， and IL-1β proteins were measured in podocytes. A drug-ingredient-target-disease interaction network for QDTS in the treatment of DN was constructed by network pharmacology methods. The key signaling pathways regulating podocyte pyroptosis were analyzed， and validation was conducted through in vivo and in vitro experiments. ResultCompared with normal group， glomerular hyperplasia and glomerular basement membrane thickening were observed in model group， and some segments were accompanied by obvious podocellular process fusion. The protein expressions of NLRP3， GSDMD and IL-1β in mouse kidney were increased， the protein expressions of mitogen-activated protein kinase 14 （MAPK14）， V-Rel reticuloendotheliosis virus oncogene homology A （RELA） and Caspase-8 in mouse kidney were increased （P<0.05）. Compared with model group， kidney pathological injury of mice in QDTS group was significantly reduced， and the expressions of NLRP3， GSDMD and IL-1β in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. The protein expressions of MAPK14， RELA and Caspase-8 in kidney of mice in QDTS group and valsartan group were decreased （P<0.05）. Network pharmacology results showed that there were 16 targets for QDTS to regulate DN cell pyrodeath， among which MAPK14， RELA and Caspase-8 were the key targets. Compared with normal glucose group， the protein expressions of NLRP3， GSDMD and IL-1β in high glucose group were increased （P<0.05）， and the protein expressions of MAPK14， RELA and Caspase-8 in mouse podocytes were increased （P<0.05）. Compared with high glucose group， the expressions of NLRP3， GSDMD and IL-1β in podocytes of mice in QDTS group were decreased （P<0.05）， and the expressions of MAPK14， RELA and Caspase-8 in podocytes of mice in QDTS group were decreased （P<0.05）. ConclusionQDTS reduces damage to DN podocytes， which is associated with its regulation of the MAPK14/RELA/Caspase-8 signaling pathway and inhibition of podocyte pyroptosis.

Objective:To explore the application value of dynamic monitoring of serum soluble interleukin-2 receptor (sIL-2R) and stromal cell-derived factor 1 α (SDF-1α) in patients with acute leukemia (AL).Methods:A total of 187 patients with AL admitted to the Second Hospital of Shanxi Medical University from March 2017 to August 2018 were selected and 90 healthy subjects at the same period were selected as the healthy controls. The levels of serum sIL-2R and SDF-1α were detected at the initial diagnosis, remission phase and relapse phase, respectively. The clinical value of dynamic monitoring of sIL-2R and SDF-1α was analyzed.Results:Among 187 patients with AL, 135 patients (72.19%) had complete remission (CR) after chemotherapy, 52 patients (27.81%) had partial remission, and 43 patients (31.85%) relapsed. The level of serum sIL-2R at the AL initial diagnosis period was (533±32) U/ml, which was higher than that in the healthy controls [(247±30) U/ml], and the difference was statistically significant ( t = 71.976, P < 0.01); the level of serum SDF-1α at the AL initial diagnosis was (2 968±305) pg/ml, which was higher than that in the healthy controls [(1 358±160) pg/ml], and the difference was statistically significant ( t = 47.043, P < 0.01). The levels of serum sIL-2R [(308±30) U/ml] and SDF-1α [(1 576±184) pg/ml] in the CR phase were lower than those in the initial diagnosis of patients with AL; and the levels of sIL-2R [(599±36) U/ml] and SDF-1α [(2 894±301) pg/ml] in the relapse phase were higher than those in the CR phase of patients with AL (all P < 0.01). Conclusions:The levels of serum sIL-2R and SDF-1α in patients with AL are increased, and there are big differences in the levels of sIL-2R and SDF-1α at the initial diagnosis, remission phase, and relapse phase. Dynamic monitoring of both can provide the data support for early clinical intervention.

Objective: To investigate the significance of endoplasmic reticulum stress-associated gene tri-bbles pseudokinase 3 (TRIB3) in the long-term brain injury in rats with developing epilepy. Methods: Thirty male SD rats aged 21 days were randomly divided into the control group and the epilepsy group, 15 rats in each group.The rats in the epilepsy group were intraperitoneally injected with kainic acid (10 mg/kg) to induce seizures, while the rats in the control group were injected with the equal volume of 9 g/L saline.The rats in two groups were euthanized at 30 d after kainic acid administration.The damage to the ultrastructure of the cortex were observed by using transmission electron microscopy.Neuronal apoptosis in the cortex of rats was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay.The expression and localization of glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein-homologous protein (CHOP), TRIB3, and the activation of protein kinase B (AKT) in the cortex were examined by using Western blot analysis and immunohistochemistry. Results: Compared with the control group, the different ultrastructural changes were observed in the cortex in the epilepsy group rats.TUNEL assay indicated that the number of apoptosis cells of cortex in the epilepsy group was increased.The protein levels of GRP78 and TRIB3 were upregulated in the cortex of the epileptic rats (1.280±0.272, 1.725±0.570), compared with the control group (1.000±0.000, 1.000±0.000), and the differences were statistically significant (all P<0.05). There was no significant change in CHOP protein between the control group and the epilepsy group.The level of phosphorylated AKT(p-AKT) was decreased in the cortex of the epilepsy group (0.150±0.047), compared with the control group (1.000±0.000), and the difference was statistically significant (P<0.05). Conclusions The brain injury caused by epilepsy in the developing rats can sustain to the stage of mature rats, and the endoplasmic reti-culum stress-associated gene TRIB3 is involved in the pathogenesis of long-term brain damage in the rats with deve-loping epilepsy.

Objective: To investigate the role of H3K27M mutant in spinal cord glioma, specifically the correlation between H3K27M mutation and histological grade or prognosis. Methods: Twenty-four cases of paraffin-embedded spinal cord glioma tissues and clinical data were collected from November 2014 to August 2016 at the Beijing Tsinghua Changgung Hospital. There were 13 males and 11 females, and the age ranged from 3 to 66 years. All the cases were reviewed histologically, and immunohistochemical H3K27M staining and H3 gene detection were performed. The correlation between H3 gene mutation and histological grading and prognosis of spinal cord gliomas were investigated and relevant literature reviewed. Results: Eleven of 24 cases showed H3K27M gene mutation, and was concordant with the result of immunohistochemistry. Gliomas in the mutant group were all high-grade gliomas with mean patients′ age of (30.0±11.5) years, and a male to female ratio of 7:4. Thirteen cases were wild-type, and these included four high-grade gliomas, with mean patients′ age (31.3±22.4) years, and a male to female ratio of 6∶7. The tumors in the mutant group were mainly located in cervical 4-7 and thoracic 11-12 segments, respectively, and the incidence of tumors in the lower thoracic segments (thoracic 11-12) was higher than that in the wild type group. Outcome data were available for all patients. The median survival of mutant group was 19.5 months, but most patients in the wild-type group were alive at the end of the follow-up period. Conclusion Gliomas of spinal cord with H3K27M mutation are high-grade and the prognosis of patients is poor.

?? [Abstract]? Objective? To explore the effect of physical cooling method by the use of external cooling ice-packs for treatment of the in-patients with fever. Methods? In accordance with the model of Australian JBI evidence-based health care, the evidence was applied to the clinical practice after evidence generation, and synthesis. Admitted from November 2017 to June 2018 into the hematology department in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, the hyperpyretic patients with blood disease were divided into two groups-observation group and control group randomly. 68 patients were included in each group. The patients in observation group were given by 0.5 g acetaminophen orally along with ice-packs while the patients in control group were just given by 0.5 g oral acetaminophen. The temperature lowering effect in both groups was compared and studied. Results? In the observation group, patients' temperature was (38.90±0.37)℃ before intervention, (38.85±0.36)℃ in 30 minutes after intervention, (38.63±0.52)℃ in 1 hour and (38.07±0.76)℃ in 2 hours. And those for control group were (38.89±0.39),(38.82±0.40),(38.58± 0.59),(37.90±0.67)℃,respectively. Repeated measurement analysis of variance indicated that patients' temperature showed significant differences at each point of time during the study in both group (Ftime=77.862,P＜ 0.01). The intervention methods in the two groups did not interact with different point of time (Finteraction=0.728, P＞0.05). The effect of intervention in different groups at different point of time was not significant (Fgroups=0.909, P＞ 0.05). Conclusions? The use of physical cooling method along with medication is proved to be not significant in the patients' temperature control. Health workers should or not select the physical cooling method based on patients' condition and willingness in order to ensure their vital signs' stability and their comfort.

Objective To investigate the role of H3K27M mutant in spinal cord glioma, specifically the correlation between H3K27M mutation and histological grade or prognosis. Methods Twenty?four cases of paraffin?embedded spinal cord glioma tissues and clinical data were collected from November 2014 to August 2016 at the Beijing Tsinghua Changgung Hospital. There were 13 males and 11 females, and the age ranged from 3 to 66 years. All the cases were reviewed histologically, and immunohistochemical H3K27M staining and H3 gene detection were performed. The correlation between H3 gene mutation and histological grading and prognosis of spinal cord gliomas were investigated and relevant literature reviewed. Results Eleven of 24 cases showed H3K27M gene mutation, and was concordant with the result of immunohistochemistry. Gliomas in the mutant group were all high?grade gliomas with mean patients′age of (30.0±11.5) years, and a male to female ratio of 7:4. Thirteen cases were wild?type, and these included four high?grade gliomas, with mean patients′age (31.3±22.4) years, and a male to female ratio of 6∶7. The tumors in the mutant group were mainly located in cervical 4-7 and thoracic 11-12 segments, respectively, and the incidence of tumors in the lower thoracic segments (thoracic 11?12) was higher than that in the wild type group. Outcome data were available for all patients. The median survival of mutant group was 19.5 months, but most patients in the wild?type group were alive at the end of the follow?up period. Conclusion Gliomas of spinal cord with H3K27M mutation are high?grade and the prognosis of patients is poor.

Objective To explore the changes of Beclin-1,P62/SQSTM1,microtubule-associated protein 1 light chain 3 (LC3)and unc-51 like autophagy activating kinase 1 (ULK-1)in the brains of the rats in the deve-lopmental stage with epilepsy. Methods Seventy-two male Sprague Dawley (SD)rats aged 21 days were randomly divided into the control group and the epilepsy group. The rats in 2 groups were randomly subdivided into 4 groups according to the time intervals (3 h,6 h,12 h and 48 h),respectively,with 9 rats in each group. The rats in the epilep-sy group were injected with kainic acid (12 mg/kg)to induce epilepsy,and the rats in the control group were injected with equal volume of saline. The rats in 2 groups were anaesthetized and sacrificed. Then,the brain tissues of the rats were quickly removed according to the time intervals. The brain damages were determined by adopting Nissl staining method. The apoptotic cells were detected by Terminal - deoxynucleoitidyl transferase mediated nick end labeling (TUNEL)assays. The expressions of Beclin-1,P62/SQSTM1,LC3 and ULK-1 mRNA levels in cortex were mea-sured by using real-time quantitative polymerase chain reaction (qPCR)analysis. Results Nissl staining indicated that many neurons were damaged performing vague outline,irregularly aligned,pyknotic nuclei and shrunken somata in the epilepsy 48 h group. In addition,there was a huge loss of neurons in cortex in the epilepsy 48 h group [(82 ± 8)num-bers],compared with the control group [(122 ± 8)numbers],and the difference was statistically significant (F＝3. 768, P＝0. 01). The apoptotic cells tremendously increased in the epilepsy 48 h group [(13 ± 7)numbers],compared with the control group [(2 ± 1)numbers]by TUNEL analysis,and the diffe-rence was statistically significant (t＝ -3. 821, P＝0. 003). qPCR showed the mRNA levels of Beclin-1,P62/SQSTM1,LC3 and ULK-1 were upregulated in the epi-lepsy 12 h group (1. 70 ± 0. 75,1. 75 ± 0. 77,1. 52 ± 0. 43,7. 48 ± 6. 12)and the epilepsy 48 h group (1. 63 ± 0. 43, 1. 48 ± 0. 74,1. 74 ± 0. 55,7. 69 ± 5. 65),compared with the control group (1. 00,1. 00,1. 00,1. 00),and the differences were statistically significant (F＝2. 820,3. 452,5. 811,5. 002,all P＜0. 05). Conclusion The autophagy activates be-fore apoptosis occurs,and autophagy-related genes probably are involved in epilepsy-induced brain damage.

Objective To compare the therapeutic effect of Midodrine hydrochloride plus oral rehydration salts,Metoprolol plus oral rehydration salts and simple oral rehydration salts on children with postural tachycardia syn-drome(POTS). Methods One hundred and ninety - two children with POTS were divided into Midodrine hydrochlo-ride plus oral rehydration salts group(84 cases),Metoprolol plus oral rehydration salts group(54 cases)and oral rehy-dration salts group(54 cases). The patients were followed up at the outpatient department after 3 - months treatment. Short - term effect was analyzed by reevaluating the symptom scores,repeating upright test and studying the side effects of the drugs. All the children were followed - up by telephone,mainly investigating on the syndrome recurrence and symptom - free survival by Kaplan - Meier analysis. The follow - up time was 3 to 122(42. 7 ± 24. 3)months. Results Short - term effect showed that the symptom scores were decreased after treatment(t = 21. 536,P ﹤ 0. 001). Head -up test showed that delta heart rate was decreased. The effective rates in the Midodrine hydrochloride plus oral rehydra-tion salts group and the Metoprolol plus oral rehydration salts group were significantly higher than those of the simple oral rehydration salts group(χ2 = 10. 905,P = 0. 004). But no statistical difference was found between the Midodrine hydrochloride plus oral rehydration salts group and the Metoprolol plus oral rehydration salts group(χ2 = 0. 042,P =0. 837). Long - term effect by Kaplan - Meier curve showed that the therapeutic effect of Midodrine hydrochloride plus oral rehydration salts group was significantly higher than any of the other two groups(χ2 = 13. 299,P ﹤ 0. 01),but no statistical difference was found between the Metoprolol plus oral rehydration salts group and the simple oral rehydration salts group(χ2 = 0. 150,P = 0. 699). Conclusions In terms of the short - term result,the effective rates in the Mido-drine hydrochloride plus oral rehydration salts group and the Metoprolol plus oral rehydration salts group were signifi-cantly higher than those of the simple oral rehydration salts group. The therapeutic effect of the Midodrine hydrochloride plus oral rehydration salts was superior to that of the Metoprolol plus oral rehydration salts and the simple oral rehydra-tion salts for POTS children by the long - term follow - up study.