Humans ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Hydrazines/therapeutic use* ; Leukemia, Myeloid, Acute/drug therapy*

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups(n=8):model control group(MC),high frequency vibration group 1 (GP₁,60 Hz),high frequency vibration 2 group (GP₂,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1^st,4 ^th and 7^th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2～5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher (P＜0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower(P＜0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower (P＜0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly (P＜0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower (P＜0.05 or P＜0.01). But the expressions of Sox9 mRNA and protein were significantly higher (P＜ 0.05 or P＜0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.
Animals ; Cartilage, Articular/metabolism* ; MAP Kinase Kinase 4 ; Male ; NF-kappa B/metabolism* ; Osteoarthritis, Knee/therapy* ; RNA, Messenger/metabolism* ; Rats ; Rats, Sprague-Dawley ; SOX9 Transcription Factor ; Vibration

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVE: To observe the effect of needle knife on chondrocyte autophagy and expressions of autophagy-related protein and mammalian target of rapamycin (mTOR) in rats with knee osteoarthritis (KOA), and to explore the possible mechanism of needle knife for KOA. METHODS: A total of 42 SD rats were randomly divided into a normal group, a model group and a needle knife group, 14 rats in each group. Except for the normal group, the other two groups were injected with the mixture of papain and L-cysteine into the left hind knee joint to establish the KOA model. After modeling, the rats in the needle knife group were treated with needle knife at strip or nodule around the quadriceps femoris and medial and lateral collateral ligament on the affected side, once a week for 3 times (3 weeks). The changes of left knee circumference in each group were observed; the chondrocytes and ultrastructure of left knee joint were observed by HE staining and electron microscope; the mRNA and protein expressions of autophagy-related genes (Atg5, Atg12, Atg4a), Unc-51 like autophagy activated kinase 1 (ULK1), autophagy gene Beclin-1 and mTOR in left knee cartilage were detected by real-time fluorescence quantitative PCR and Western blot. RESULTS: After modeling, the left knee circumferences in the model group and the needle knife group were increased compared with those before modeling and in the normal group (P<0.05); after intervention, the left knee circumference in the needle knife group was smaller than that in the model group and after modeling (P<0.05). Compared with the normal group, the number of chondrocytes was decreased, and a few cells swelled, nuclei shrank, mitochondria swelled and autophagosomes decreased in the model group; compared with the model group, the number of chondrocytes was increased , and most cell structures returned to normal, and autophagosomes was increased. Compared with the normal group, the mRNA and protein expressions of Atg5, Atg12, Atg4a, Beclin-1 and ULK1 in the knee cartilage in the model group were decreased (P<0.05); compared with the model group, the expressions of the above indexes in the needle knife group were increased (P<0.05). Compared with the normal group, the mRNA and protein expressions of mTOR in the knee cartilage in the model group were increased (P<0.05); compared with the model group, the expressions of the above indexes in the needle knife group were decreased (P<0.05). CONCLUSION The needle knife intervention could improve knee cartilage injury in rats with KOA, and its mechanism may be related to reducing the expression of mTOR and up-regulating the expressions of Atg5, Atg12, Atg4a, ULK1 and Beclin-1, so as to promote chondrocyte autophagy and delay the aging and degeneration of chondrocytes.
Animals ; Autophagy ; Autophagy-Related Protein-1 Homolog/genetics* ; Beclin-1/genetics* ; Chondrocytes ; Osteoarthritis, Knee/therapy* ; Rats ; Rats, Sprague-Dawley ; TOR Serine-Threonine Kinases/genetics*

ObjectiveTo explore the effect of Ganshuang granule on liver fibrosis （S1 and S2） in chronic hepatitis B （CHB） with liver depression spleen deficiency and blood stasis syndrome. MethodA total of 100 patients were classified into the control group （50 in total with 4 lost and 2 rejected， 44 finally included） and observation group （50 in total with 5 lost and 2 rejected， 43 finally included） with the random number table method. Both groups were given oral entecavir tablets （0.5 mg/time， once a day， 12 months）， and oral glutathione tablets was applied depending on the conditions of patients. In addition， the control group took the analog drug of Ganshuang granule （3 g/time， 3 times/day， 12 months） and the observation group received Ganshuang granules （3 g/time， 3 times/day， 12 months）， followed by histological examination of the liver by puncture biopsy. The two groups were compared in terms of inflammatory activity grade and fibrosis stage， as well as liver stiffness measure （LSM）， liver function， hepatitis B virus （HBV） DNA， liver depression and spleen deficiency syndrome score， aspartate aminotransferase （AST）-to-platelet ratio index （APRI）， and fibrosis index based on the four factors （FIB-4）. ResultAfter treatment， liver fibrosis in the observation group was milder than that in the control group （P<0.05） and the inflammatory activity grade in the observation group was lower than that in the control group （P<0.05）. The effective rate in down-regulating inflammatory activity grade in the observation group was 77.78% as compared with the 45.83% in the control group （χ²=5.546， P<0.05）. The effective rate in decreasing the fibrosis stage in the observation group was 59.26%， which was higher than that （16.67%） in the control group （χ²=9.669， P<0.01）. The LSM and score of the liver stagnation and spleen deficiency syndrome in the observation group were lower than those in the control group at the 6th months and 12th months of treatment （P<0.05，P<0.01）. The levels of alanine aminotransferase （ALT）， AST， and alkaline phosphatase （ALP） in the observation group were lower than those in the control group （P<0.01）. The APRI and FIB-4 in the observation group were lower than those in the control group （P<0.01）. ConclusionThe Ganshuang granule combined with entecavir can alleviate inflammation and liver fibrosis， delay and reverse liver fibrosis， protect liver， and improve the traditional Chinese medicine syndrome of liver fibrosis （S1 and S2） in CHB， which is worth of clinical use and further research.

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

OBJECTIVE: To investigate the effect of baicalein on polymicrobial sepsis-induced immune dysfunction and organ injury. METHODS: A sepsis model was induced in Sprague-Dawley rats via caecal ligation and puncture (CLP). Specific pathogen free rats were randomly divided into a sham group, CLP group and CLP + baicalein (Bai) group (n=16 each). Rats in the CLP + Bai group were intravenously injected with baicalein (20 mg/kg) at 1 and 10 h after CLP. Survival rate, bacterial load, and organ damage were assessed. Then each group was evaluated at 6, 12, and 24 h to investigate the effect of baicalein on immune cells and inflammatory cytokines in septic rats. RESULTS: Baicalein treatment significantly improved the survival of septic rats, decreased the bacterial burden, and moderated tissue damage (spleen, liver, and lung), as observed by haematoxylin and eosin staining. Septic rats treated with baicalein had strikingly increased proportions of CD3⁺CD4⁺ T cells and ratios of CD4⁺/CD8⁺ T cells in the peripheral blood and spleen (all P<0.05). Moreover, baicalein treatment decreased the apoptotic rate of whole white blood cells and spleen cells at 24 h after surgery (P<0.05). Baicalein significantly reduced the levels of tumor necrosis factor α and interleukin-6 (IL-6) and increased IL-10, and the expression levels of galectin 9 were also raised in the spleen (P<0.01). CONCLUSION Baicalein may be an effective immunomodulator that attenuates overwhelming inflammatory responses in severe abdominal sepsis.
Animals ; CD8-Positive T-Lymphocytes ; Flavanones ; Inflammation/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Sepsis/drug therapy*

OBJECTIVE: To investigate the effect of Kangquan Recipe (, KQR) on bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) expression and its mechanism in rats with benign prostatic hyperplasia (BPH). METHODS: Forty-eight male Sprague-Dawley rats were divided into 6 groups using a random number table, with 8 in each group: the normal group (normal saline 10 mL/kg), the model group (normal saline 10 mL/kg), the finasteride group (0.5 mg/kg), the low-dose KQR group (3.5 g/kg), the middle-dose KQR group (7 g/kg), and the high-dose KQR group (14 g/kg). The 40 rats were subcutaneously injected with testosterone propionate after castration for 30 days to establish the BPH rat model except for those in the normal group. At the same time, the corresponding drugs were administered by gavage for 30 consecutive days. The effects of different doses of KQR on the protate wet weight, prostate volume and prostate index (PI) were observed. The changes in histopathology were monitored with hematoxylin-eosin staining. BAMBI protein and mRNA expression contents were determined by Western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS: All doses of KQR could decrease prostatic epithelial tissue proliferation. Compared to the model group, the high and middle-dose KQR significantly reduced prostate wet weight, prostate volume and PI; increased BAMBI protein expression in the hypothalamus, pituitary and prostate tissue; all doses of KQR up-regulated BAMBI mRNA expression in serum, prostatic fluid and prostate tissue (P<0.05 or P<0.01). CONCLUSIONS KQR could inhibit the proliferation of rat prostatic tissue, promote BAMBI protein expression in the hypothalamic-pituitary-prostate of rats with BPH; and increase BAMBI mRNA expression in the blood, prostatic fluid and prostate tissue of rats with BPH, showing a dose-effect relationship. KQR can be used as a potential drug for the treatment of BPH.

Objective: Huidouba (HDB) is a Chinese folk medicine used to treat diabetes in Sichuan Province, China. Therefore, we investigated the anti-diabetic effects of HDB and its underlying mechanisms. We hypothesized that HDB treatment could enhance glucose tolerance and insulin sensitivity, and thus prevent a hyperglycemia state. Methods: To test the hypothesis, streptozotocin (STZ)-induced diabetic mice and db/db mice, widely used models of hyperglycemia and insulin-resistant diabetes, were either treated with HDB, metformin, or acarbose. Blood glucose, oral glucose tolerance test, insulin tolerance test, pancreatic histopathology and serum biochemistry were detected to assess the hypoglycemic effect of HDB. Results: HDB treatments were found to show the effect in reducing glucose levels. HDB also resulted in a significant reduction in body weight and food intake in the STZ-induced diabetic mouse model. Furthermore, it significantly improved glucose and insulin tolerance in the two diabetic mouse models. Importantly, insulin, glucagon, pancreatic polypeptide, and somatostatin immunohistochemistry revealed that HDB treatment improved the function and the location of the cells in the islets compared with the other two treatments. HDB treatment resulted in significant restoration of islet function. Our results illustrated the underlying mechanism of HDB in the progression of diabetes, and HDB can be an effective agent for the treatment of diabetes. Conclusion: The results of this study suggested that HDB can reduce blood glucose levels in STZ-induced hyperglycemic mice and db/db mice.

Objective:From a new perspective，to explore therapeutic effect of Huidouba (HDB) on alleviating kidney oxidative damage in rats with diabetic nephropathy (DN) and provide a scientific basis for developing HDB as a potential Tibetan medicine for treatment of DN. Method:Rats were fed with high-fat diet (HFD) and injected with streptozocin (STZ, 65 mg·kg^-1) intraperitoneally to induce DN model, while rats in Blank group were injected with an equal volume of vehicle and fed with normal chow. The successfully modeling DN rats were randomly divided into three groups, 8 rats per group, DN model group (10 mL·kg^-1·d^-1), Metformin group (0.045 g·kg^-1·d^-1) and HDB group (0.18 g·kg^-1·d^-1). Monitor body weight (BW) and fasting blood glucose (FBG) weekly, and collect 24 hours urine before and after medication to examine microalbuminuria (mAlb). Calculate kidney index (KI) after sacrificing, analyze mAlb, serum creatinine (SCr) and blood urea nitrogen (BUN) with a fully automatic biochemical analyzer. Histopathology of kidney was observed by Masson staining. Lipid peroxidation malondialdehyde (MDA) assay kit was used to examine MDA content in kidney tissue. Nox4, as a subtype of triphosphopyridine nucleotide (NADPH) oxidase family was determined by Western blot and immunofluorescence assay of kidney tissue. Result:Compared with blank group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in DN model group were increased (P<0.01), tissue damage was obvious and Nox4 expression in glumeruli was increased significantly (P<0.01). Compared with DN model group, levels of FBG, 24 h mAlb, SCr, BUN and MDA in drug administration groups were decreased (P<0.01), kidney injury was alleviated and Nox4 expression was down-regulated（P<0.01）. Conclusion:HDB as a Yiqiyangyin Tibetan medicine, could ease oxidative stress injury of kidney and reduce proteinuria in DN rats, thus prevent the development of DN. Its mechanism is closely related to down-regulating Nox4 expression of kidney tissue in DN rats.