Purpose::Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation.Methods::C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. Results::Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol.Conclusions::Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

OBJECTIVES: To study the cooling reaction kinetic characteristics of the temperature difference between cadaver temperature and ambient temperature (hereinafter referred to as "cadaver temperature difference") according to the reaction kinetics method. METHODS: Thirty rabbits were randomly divided into 5 groups with 6 rabbits in each group. The rabbits were injected with 10% potassium chloride solution intravenously. After death, the rabbits were placed at 5 ℃, 10 ℃, 15 ℃, 20 ℃ and 25 ℃ environment condition, respectively, and the rectal temperature was measured every minute for 20 hours. The measured cadaver temperature was subtracted from ambient temperature, and the cadaver temperature difference data was calculated using the reaction kinetics formula. The linear regression equation was fitted for analysis, and the experimental results were applied to the temperature difference data of human body after death for verification. RESULTS: Under different environmental conditions, the linear coefficient determination of temperature difference -ln(C/C₀) in rabbits was 0.99, showing a good linear relationship with time t. The application of human body temperature data after death was consistent with the results of animal experiments. CONCLUSIONS Under stable conditions, the temperature difference cooling process after death in rabbits is a first-order kinetic response. The method can also be used to study the temperature difference in human body after death.
Animals ; Humans ; Rabbits ; Body Temperature ; Temperature ; Kinetics ; Cadaver

In this study, 280 batches of Zingiberis Rhizoma samples from nine producing areas were analyzed to obtain infrared spectral information based on near-infrared spectroscopy(NIRS). Pluralistic chemometrics such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), orthogonal partial least squares-discriminant analysis(OPLS-DA), K-nearest neighbors(KNN), support vector machine(SVM), random forest(RF), artificial neural network(ANN), and gradient boosting(GB) were applied for tracing of origins. The results showed that the discriminative accuracy of the spectral preprocessing by standard normal variate transformation coupled with the first derivative was 93.9%, which could be used for the construction of the discrimination model. PCA and PLS-DA score plots showed that samples from Shandong, Sichuan, Yunnan, and Guizhou could be effectively distinguished, but the remaining samples were partially overlapped. As revealed by the analysis results by machine learning algorithms, the AUC values of KNN, SVM, RF, ANN, and GB algorithms were 0.96, 0.99, 0.99, 0.99, and 0.98, respectively, with overall prediction accuracies of 83.3%, 89.3%, 90.5%, 91.7%, and 89.3%. It indicated that the developed model was reliable and the machine learning algorithm combined with NIRS for origin identification was sufficiently feasible. OPLS-DA showed that Zingiberis Rhizoma from Sichuan(genuine producing areas) could be significantly distinguished from other regions, with good discriminative accuracy, suggesting that the NIRS established in this study combined with chemometrics can be used for the identification of Zingiberis Rhizoma from Sichuan. This study established a rapid and nondestructive identification and reliable data analysis method for origin identification of Zingiberis Rhizoma, which is expected to provide a new idea for the origin tracing of Chinese medicinal materials.
Algorithms ; Chemometrics ; China ; Ginger ; Least-Squares Analysis ; Plant Extracts ; Principal Component Analysis ; Support Vector Machine

Objective: To investigate the clinical effects of in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage in the treatment of hypertrophic scar in non-functional sites after burns. Methods: A retrospective observational study was used. From June 2017 to June 2019, 33 patients (24 males and 9 females, aged 8-50 years) who met the inclusion criteria with hypertrophic scars in non-functional sites outside the face after burns were treated in General Hospital of TISCO (the Sixth Hospital of Shanxi Medical University). All patients underwent scalp transplantation after perforation of retained split scar matrix in situ (with scar thinning area of 90-500 cm²), and then the vacuum sealing drainage was performed. The hematoma and infection of wounds were observed on the 7^th day after operation. At the same time, the survival rate of skin grafting was observed and calculated. The flatness and thickness of the scar in the operative area were observed in 12 months after operation, and the itching and pain of the patients were recorded. Vancouver Scar Scale was used to score the scar of patients before operation and at 3, 6 and 12 months after operation. The healing time and hair growth of donor site were observed. Data were statistically analyzed with repeated analysis of variance, paired sample t test and bonferroni correction. Results: On the 7^th day after operation, local subcutaneous hematoma appeared in the wound of 2 patients, which healed after dressing change; no infection occurred. On the 7^th day after operation, the survival rate of skin grafting of patients was 94.6%-99.0%(96.8±1.2)%. Scar flatness was well, the thickness of scar was not significantly higher than that of normal skin in 12 months after operation, and the symptoms of itching pain of patients disappeared or significantly relieved. Vancouver Scar Scale scores of patients before operation and at 3, 6, and 12 months after operation were 12.1±2.8, 8.5±1.5, 7.6±1.6, 6.7±1.3, respectively, and the scores of 3, 6, and 12 months after operation were all significantly lower than that before operation (with t values of 4.48, 4.06, and 3.97, respectively, P<0.01). All the donor sites of the head healed well in 4-7 days after operation. By 3-6 months after operation, all patients had good hair growth in the donor site and achieved no scar healing. Conclusions: The treatment of hypertrophic scar in non-functional sites outside the face after burns by in situ perforation of preserved split scar matrix in combination with scalp transplantation and vacuum sealing drainage can effectively improve the appearance of hypertrophic scar in non-functional areas after burn and reduce its degree of hyperplasia, with scar-free donor site healing.
Adolescent ; Adult ; Burns/surgery* ; Child ; Cicatrix, Hypertrophic/surgery* ; Female ; Humans ; Male ; Middle Aged ; Negative-Pressure Wound Therapy ; Scalp/surgery* ; Skin Transplantation ; Young Adult

Elaphurus davidianus( Milu),a rare animal unique to China,has been used as medicine for more than a thousand years,but the extinction of Milu in modern times resulted in the unavailability of related medical products. Today,the reintroduction of Milu population makes it possible to restore its medicinal usage. The resource reserves of Cervi Cornu,the natural shedding product from Milu,are increasing with the expansion of the population,allowing it to be fully utilized in the medical field. Mijiao Pills,first recorded in Important Prescriptions Worth a Thousand Gold for Emergency( Bei Ji Qian Jin Yao Fang) by Sun Simiao in the Tang Dynasty,is the first Chinese medicinal prescription with Cervi Cornu as the sovereign medicinal,which is effective in tonifying. Its composition,preparation,efficacy and indications,and administration are described in detail in the Important Prescriptions Worth a Thousand Gold for Emergency,which however,have changed significantly over the thousands of years,seriously affecting the clinical application of this classical prescription and related product development. Therefore,the key information of this prescription should be systematically collated and summarized. According to the principles of textual research on key information in ancient classical prescriptions promulgated by relevant authorities,this paper reviewed ancient Chinese medical books of the past dynasties,modern literature,as well as the Pharmacopoeia of the People's Republic of China( 2020 Version) to figure out such key information as the source,historical evolution,original plants and animals and their processing,dosage,preparation,and usage of Mijiao Pills. This paper aimed to provide a basis for the clinical application of Mijiao Pills and subsequent product development,thus facilitating the development and utilization of this precious medicinal animal resource.
Books ; China ; Cornus ; Humans ; Medicine, Chinese Traditional ; Prescriptions

Animals ; Brain-Derived Neurotrophic Factor ; Depression/drug therapy* ; Fluoxetine ; Mice ; Stress, Psychological ; Transcranial Magnetic Stimulation

It is known that silibinin has antioxidant, anti-tumor, anti-inflammatory and immunomodulatory effects, and which is widely used for liver damage caused by a variety of reasons. In recent years, it is found that silibinin has potential anti-allergic reactions. However, even larger doses of silibinin still show no significant side effects . The rare literature reports that silibinin can cause allergic reactions. The paper reports a middle-aged patient who orally took silibinin for the prevention of tuberculosis chemotherapy-induced liver damage, and he occurred symptoms of lip pain and anabrosis, foreign body sensation, and difficulty eating one day after treatment. The patient was misdiagnosed as"vesicular stomatitis"and was treated by anti-viral therapy. The patient was discharged from the hospital after treating allergic reactions. As a safe and effective drug for prevention of liver damages in clinic, silibinin should be alert to induce possible allergies when there are local skin manifestations such as lip pain and anabrosis.

Beads, a novel drug delivery system self-assembled by cyclodextrins (CDs) and oil, has potential applications in the solidification of oil drugs and improving the bioavailability of lipid-soluble drugs. However, very few researches were dedicated to the mechanism of beads formation. In this study, three-dimensional structures of beads were visualized and investigated using synchrotron radiation X-ray microcomputed tomography (SR-μCT). The structural changes of beads attributed by drying process were analyzed and confirmed via visualization results of SR-μCT. Productively, it was proposed that Pickering emulsion droplets obtained during beads formation process were spatially localized orderly. Moreover, the effects of loading lipid soluble drug, namely, vitamin K₁, on the structural changes of beads were also analyzed. It is well known that the surface tension of oil phase could be changed by the addition of lipid soluble constituents. It was reasonable that the three-dimensional structure of beads might be altered during the drug loading of vitamin K₁ into the beads. However, although the morphologies of beads were changed to some extent, the ordered Pickering emulsion droplets during the process of beads formation was successfully illustrated based on the SR-μCT results. Conclusively, according to the three-dimensional structural analysis of the beads, this study revealed the organized architecture for Pickering emulsion droplet assembly and beads formation in cyclodextrin semi-inclusion complex, which significantly complements the formation mechanism of beads, and provides a structural basis for the further study of beads.