Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous study found that oral administration of nitazoxanide inhibited Western diet (WD)-induced hepatic steatosis in ApoE^-/- mice. However, the specific mechanism remains to be elucidated. In the present study, we performed an untargeted metabolomics approach to reveal the effect of nitazoxanide on the liver metabolic profiles in WD-fed ApoE^-/- mice, and carried out the cellular experiments to elucidate the underlying mechanisms. UPLC-MS-based untargeted metabolomics analysis was used to investigate the effect of nitazoxanide on global metabolite changes in liver tissues. The differential metabolites were screened for enrichment analysis and pathway analysis. Hepatocytes were treated with tizoxanide, the metabolite of nitazoxanide, to investigate the underlying mechanism based on the findings in metabolomics study. The improvement of liver lipid metabolism disorders by nitazoxanide treatment in WD-fed ApoE^-/- mice was mainly through regulating glycerophospholipid metabolism, D-glutamine and glutamate metabolism, glutathione metabolism, and arginine biosynthesis metabolism. Tizoxanide, the active metabolite of nitazoxanide, increased glutathione (GSH) contents and glutamate-cysteine ligase catalytic subunit (Gcl-c) and glutathione reductase (Gsr) mRNA expressions in HepG2 cells. Tizoxanide increased cystathionine β-synthase (CBS) and phosphatidylethanolamine N-methyltransferase (PEMT) protein levels, inhibited lipid accumulation in hepatocytes induced by free fatty acid (FFA). Tizoxanide increased S-adenosyl-L-homocysteine hydrolase (SAHH) protein levels in HepG2 cells and mouse primary liver cells stimulated with free fatty acid (FFA). Tizoxanide increased N-acetyl glutamate synthase (Nags) and carbamoylphosphate synthetase 1 (Cps1) mRNA expressions in HepG2 cells. In conclusion, nitazoxanide improves WD-induced hepatic steatosis in ApoE^-/- mice and the underlying mechanisms include increasing CBS expression, GSH content, PEMT protein expression, Nags and Cps1 mRNA expression in hepatocytes.

Aortic valve stenosis,as a common heart valve disease,progresses rapidly and has a poor clinical prognosis.In the case of combined acute heart failure,the pumping function of the heart is severely impaired,which may lead to a significant decrease in cardiac output,resulting in a state of shock.Transcatheter aortic valve replacement(TAVR)has become a first-line treatment for elderly patients with aortic valve stenosis since its first successful case in 2002.In China,with the advancement of technology and the strengthening of physician training,the capacity of grassroots hospitals in TAVR treatment is increasing.This case reports a patient with severe aortic valve stenosis accompanied by acute heart failure and shock status who received emergency TAVR treatment at a grassroots hospital.Due to limitations in conditions,TAVR was urgently implemented without extracorporeal circulation and extracorporeal membrane oxygenation support.The patient's blood pressure immediately rose to 105/65 mmHg after valve dilation during surgery,and the postoperative symptoms were significantly relieved.Follow up color Doppler ultrasound showed that the stenosis was relieved and the heart function was significantly improved.The success of this surgery provides a reference for emergency TAVR treatment in patients with severe aortic valve stenosis and heart failure in grassroots hospitals.

Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3％,and the complete remission(CR)rate after treatment was 33.3％.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.

This study investigated the drug delivery performance of oral co-loaded puerarin(PUE) and daidzein(DAZ) mixed micelles(PUE/DAZ-FS/PMMs) from the perspectives of pharmacokinetics, pharmacodynamics, and tissue distribution. The changes in PUE plasma concentration in rats were evaluated based on PUE suspension, single drug-loaded micelles(PUE-FS/PMMs), and co-loaded micelles(PUE/DAZ-FS/PMMs). Spontaneously hypertensive rats(SHR) were used to monitor systolic blood pressure, diastolic blood pressure, and mean arterial pressure for 10 weeks after administration by tail volume manometry. The content of PUE in the heart, liver, spleen, lung, kidney, brain, and testes was determined using LC-MS/MS. The results showed that compared with PUE suspension and PUE-FS/PMMs, PUE/DAZ-FS/PMMs significantly increased C_(max) in rats(P<0.01) and had a relative bioavailability of 122%. The C_(max), AUC_(0-t), AUC_(0-∞), t_(1/2), and MRT of PUE/DAZ-FS/PMMs were 1.77, 1.22, 1.22, 1.17, and 1.13 times higher than those of PUE suspension, and 1.76, 1.16, 1.08, 0.84, and 0.78 times higher than those of PUE-FS/PMMs, respectively. Compared with the model control group, PUE/DAZ-FS/PMMs significantly reduced systolic blood pressure, diastolic blood pressure, and mean arterial pressure in SHR rats(P<0.05). The antihypertensive effect of PUE/DAZ-FS/PMMs was greater than that of PUE suspension, and even greater than that of PUE-FS/PMMs at high doses. Additionally, the distribution of PMMs in various tissues showed dose dependency. The distribution of PMMs in the kidney and liver, which are metabolically related tissues, was lower than that in the suspension group, while the distribution in the brain was higher than that in the conventional dose group. In conclusion, PUE/DAZ-FS/PMMs not only improved the bioavailability of PUE and synergistically enhanced its therapeutic effect but also prolonged the elimination of the drug to some extent. Furthermore, the micelles facilitated drug penetration through the blood-brain barrier. This study provides a foundation for the development of co-loaded mixed micelles containing homologous components.
Rats ; Animals ; Micelles ; Tissue Distribution ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Rats, Inbred SHR ; Isoflavones/pharmacology*

OBJECTIVE: To evaluate the clinical outcomes of reverse total shoulder arthroplasty as a revision procedure for the failed fixation of proximal humeral fractures in the elderly patients. METHODS: A retrospective analysis was performed on 8 patients with failed internal fixation of proximal humeral fractures from May 2014 to March 2020, including 3 males and 5 females, aged from 65 to 75 years old. All 8 patients underwent reverse total shoulder arthroplasty, and the mean time between initial fixation and reverse total shoulder arthroplasty ranged from 8 to 16 months. Range of motion(ROM), University of California at Los Angeles(UCLA) shoulder score, visual analogue scale (VAS), self-rating anxiety scale(SAS), and Constant-Murley score of shoulder function were assessed pre-operatively and at the last follow-up. Complications relating to the surgery were recorded. RESULTS: All 8 patients successfully followed up. The mean follow-up after reverse total shoulder arhroplasty ranged from 16 to 28 months. The range of motion (forward flexion, external rotation, abduction and internal rotation) of the affected shoulder was significantly improved after surgery, and the post-operative VAS, SAS and UCLA scores were also significantly improved. For the Constant-Murley score of shoulder joint function, the total scores and the subscores of pain, daily activities, range of motion and strength test at the last follow-up were all significantly improved. Scapular glenoid notch was observed in patient, which was evaluated as grade 1 on imaging. All the other patients did not develop specific or non-specific complications. CONCLUSION Reverse total shoulder arhroplasty is an appropriate treatment as a revision surgery for failed fixation of proximal humeral fractures. It has shown satisfactory clinical outcomes, accelerating the rehabilitation of shoulder function and improving the quality of life.
Male ; Female ; Humans ; Aged ; Shoulder/surgery* ; Arthroplasty, Replacement, Shoulder/methods* ; Retrospective Studies ; Treatment Outcome ; Quality of Life ; Shoulder Joint/surgery* ; Shoulder Fractures/surgery* ; Humerus/surgery* ; Range of Motion, Articular

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990^th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.
Female ; Humans ; Male ; Burns/surgery* ; Cicatrix ; Eosine Yellowish-(YS) ; Hyaluronic Acid/therapeutic use* ; Hyperplasia ; Ki-67 Antigen ; Prospective Studies ; Umbilical Cord ; Vimentin ; Young Adult ; Adult ; Middle Aged

Humans ; Squamous Cell Carcinoma of Head and Neck ; RNA, Messenger ; Immunohistochemistry ; Papillomavirus Infections/diagnosis* ; Oncogene Proteins, Viral/genetics* ; Head and Neck Neoplasms ; Cyclin-Dependent Kinase Inhibitor p16 ; Papillomaviridae ; Papillomavirus E7 Proteins/genetics* ; DNA, Viral

Objective:To investigate the efficacy and safety of black tomato concentrated sauce in the treatment of benign prostatic hyperplasia(BPH) with lower urinary tract symptoms(LUTS).Methods:An open, randomized and controlled trial was conducted, and 150 BPH patients with LUTS were randomly assigned to three groups: experimental group(60 cases), placebo group (45 cases) and positive control group(45 cases) in the Department of Urology, Lanzhou University Second Hospital from December 2018 to September 2020.Inclusion criteria: age≥50 years old; first diagnosis of BPH, or interrupted medical treatment of BPH for more than 1 month; maximum urinary flow rate (Q max) <15ml/s; prostate volume (PV)≥20ml; IPSS≥8, QOL≥2. Exclusion criteria: lower urinary tract obstruction not caused by BPH, post-void residual urine volume(PVR) >250 ml; history of acute urinary retention in the last 3 months; prostate nodules and suspected prostate cancer were revealed by digital rectal examination and transrectal B-ultrasoundor; prostate-specific antigen (PSA)≥10 ng/ml; neurogenic bladder, perivous history of bladder, prostate, or urethra operations; suffering from serious heart, lung, liver, kidney and other diseases. The patients in the experimental group were orally treated with black tomato concentrated sauce(30 g/once, 3 times/day). The patients in the placebo group were orally administrated with placebo. In the positive control group, the patients with PV≤30ml were orally treated with tamsulosin(0.2mg/once, 1 time/day), the patients with PV>30ml were orally administrated with tamsulosin and finasteride(5 mg/once, 1 time/day). All enrolled patients were treated for 3 months. At the end of third month, the IPSS, QOL, PV, PVR, Q max, average urinary flow rate(Q ave), total PSA(tPSA), free PSA (fPSA), testosterone(TST) and the incidence of adverse reaction were assessed. Results:128 of 150 cases, including 52 cases in experimental group, 36 cases in placebo group and 40 cases in positive control group, completed the study, the rest was excluded due to not take medication regularly and fail to follow-up. There were no significant differences in baseline parameters among experimental group, placebo group and positive control group ( P>0.05) in age[(63.21±8.61) vs.(62.36±6.32) vs. (63.94±7.78)years old], body mass index[(23.74±3.17) vs. (23.94±3.09) vs. (24.26±2.91)kg/m 2], IPSS[(17.5±6.6) vs. (15.4±5.8) vs. (17.9±6.8)], QOL[4.0(3.0, 4.0) vs. 4.0(3.0, 4.5) vs. 4.0(3.0, 5.0)], Q max [(8.60±3.04) vs. (9.13±2.92) vs. (9.58±3.26) ml/s], Q ave[(4.39±1.69) vs. (4.66±1.76) vs. (4.88±1.60)ml/s], PV [32.00(25.55, 45.40)vs. 30.00(24.45, 38.35)vs. 34.80(27.65, 56.65)ml], PVR[23.50(8.25, 45.75) vs.5.50(0, 47.75) vs. 29.00(0, 84.00)ml], tPSA [1.53(0.89, 3.00) vs. 1.23(0.69, 1.98) vs. 2.23(0.90, 4.15)ng/ml], fPSA [0.37(0.28, 0.76) vs. 0.37(0.22, 0.52) vs. 0.54(0.30, 0.97) ng/ml] and TST[(443.64±156.32) vs. (493.97±176.16) vs. (450.89±135.08)ng/dl]. After 3 months of treatment, the IPSS in experimental group was(9.9±5.7), QOL score 2.0(2.0, 3.0), Q max(11.78±5.24)ml/s, Q ave(5.86±3.00)ml/s, tPSA 1.64(0.96, 3.32)ng/ml and TST (475.91±177.33)ng/dl, which were significantly different compared with pre-treatment( P<0.05). In positive control group, IPSS was (9.0±6.2), QOL 2.0(2.0, 3.0), Q max(11.73±4.50)ml/s, Q ave(6.11±2.53)ml/s, tPSA 1.57(0.80, 3.09)ng/ml, fPSA 0.37(0.24, 0.63)ng/ml and TST (526.11±126.88)ng/dl, which were statistically different compared with pre-treatment( P<0.01). However, there were no significant differences in all the above indexes in placebo control group compared with the baseline( P>0.05). The numerical changes of IPSS, QOL, Q maxand Q ave between experimental group and placebo group had statistically significant differences ( P<0.05). The changes of IPSS, QOL, Q max, Q ave, PV, tPSA, fPSA and TST between positive control group and placebo group had significant differences ( P<0.05). The changes of PV, tPSA and fPSA between positive control group and experimental group had statistically significant differences ( P<0.05). The incidence of adverse reactions was 5.77% (3/52, including 1 headache and 2 stomach discomfort) in experimental group, 5.56% (2/36, including 1 headache and 1 stomach discomfort) in placebo group, and 10.00%(4/40, including 1 dizzy, 1 nasal obstruction and 2 erectile dysfunction) in positive control group. And there was no statistical difference in the incidence of adverse reactions among three groups ( P>0.05). Conclusions:Black tomato concentrated sauce shows an excellent effect on patients with LUTS/BPH, and improves the quality of life with few adverse events.

OBJECTIVES: To investigate the relationship between the perpetrator's sex, victim's position and slashing location as well as anthropometric parameters on distance and space required for slashing, to provide the theoretical basis for the judgment of whether the crime scene was consistent with the criminal activity space. METHODS: The kinematics data of 12 male and 12 female subjects slashing the neck of standing and supine mannequins as well as the chest of the standing mannequins with a kitchen knife were obtained by using a 3D motion capture system. The relationship between the perpetrator's sex-victim's position, the perpetrator's sex-slashing location, and anthropometric parameters and the distance and space required for the slashing were analyzed by two-factor repeated measures ANOVA and Pearson correlation analysis respectively. RESULTS: Compared with slashing the neck of supine mannequins, the distance (L) and normalized L (l) of slashing the neck of standing mannequins were greater, while vertical distance (L_VR) and normalized L_VR (l_VR) of the knife side were smaller. Compared with slashing the neck of standing mannequins, the L and l slashing the chest of standing mannequins were greater, while L_VR and l_VR were smaller. Horizontal distance (L_HR) and normalized L_HR (l_HR) of the knife side in males were greater than that in females. Height and arm length were positively correlated with L, L_HR, and L_VR when striking the standing mannequins. CONCLUSIONS When slashing the neck of supine or standing victims, the slashing distance is shorter and the slashing height is greater. Furthermore, the distance and space required for slashing are correlate with anthropometric parameters.
Humans ; Male ; Female ; Motion Capture ; Crime ; Biomechanical Phenomena

OBJECTIVE: To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients. METHODS: Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared. RESULTS: There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group. CONCLUSION The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.
Antineoplastic Combined Chemotherapy Protocols ; Decitabine/therapeutic use* ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Retrospective Studies ; Treatment Outcome ; Tretinoin/therapeutic use*