OBJECTIVETo study the effect of methylprednisolone (MP) on reperfusion injury in severe uncontrolled hemorrhagic shock and explore the possible mechanism involved.

METHODSTwelve dogs were randomly divided into two groups, control group (Group I, n=6) and MP group (Group II, n=6). The animals were bled continuously from a femoral artery catheter to produce uncontrolled hemorrhagic shock models. Resuscitation with lactated Ringer's (LR) solution was initiated when mean arterial pressure (MAP) decreased to 20 mm Hg, and MAP was maintained at 30-40 mm Hg. MP (4 mg/kg) was injected intravenously in Group II when resuscitation began. While in Group I, normal saline (NS) was injected instead. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured before exsanguination (T(1)), when MAP decreased to 20 mm Hg (T(2)), 60 min (T(3)) and 120 min (T(4)) after resuscitation. Heart rate, MAP and cardiac output (CO) levels were recorded concomitantly.

RESULTSInfusion volume and hemorrhage volume shed from the superior mesenteric artery in Group I were higher than those in Group II (P<0.01 and P<0.05). After reperfusion, blood SOD levels decreased progressively and MDA levels increased rapidly in Group I. In Group II, blood SOD levels at T(3) and T(4) decreased as compared with that at T(1) but a stepwise increase was present. At T(4), blood SOD level was significantly higher in Group II than in Group I (Plt;0.01). At T(3) and T(4), MDA levels were markedly lower in Group II than in Group I. During reperfusion, MAP was more steady in Group II than in Group I and survival rate after 120 min (at T(4)) was higher in Group II than in Group I (P<0.05).

CONCLUSIONSMP has a protective effect on severe uncontrolled hemorrhagic shock and subsequent reperfusion injury. The mechanism mainly involves the anti-lipid peroxidation activity of MP.

Analysis of Variance ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Lipid Peroxidation ; Male ; Methylprednisolone ; pharmacology ; Probability ; Random Allocation ; Reference Values ; Reperfusion Injury ; drug therapy ; physiopathology ; Sensitivity and Specificity ; Shock, Hemorrhagic ; drug therapy ; physiopathology ; Survival Rate

Abstract: Objective To explore the trend of maternal mortality in Hainan Province during the period of 2003-2022, both in the province and in urban and rural areas, and to forecast the maternal mortality rate for the period 2023-2025. Methods The 2003-2022 data collected from Hainan Province's three-tier network for maternal mortality surveillance was examined using the Chi-square test for trend (CMH) to analyze the province-wide and urban-rural maternal mortality trends. The time series model forecasting using exponential smoothing was used to predict the maternal mortality rate in Hainan Province from 2023 to 2025. Results　From 2003 to 2022, a total of 201 011 616 live births and 463 maternal deaths were reported in Hainan Province, with a maternal mortality rate of 23.03 per 100 000. Over 20 years, the maternal mortality rate in Hainan Province showed a downward trend, with an annual rate of decline of -4.13%. The rate decreased significantly during this period.. From 2003 to 2022, the maternal mortality rate in rural areas of Hainan Province was 25.74/100 000 (373/1 448 943), and it was significantly higher than that in urban areas, 16.04/100 000 (90/561 173). In the first 10 years, the gap between urban and rural areas progressively reduced, but it widened significantly in the last decade, especially after 2017. The maternal mortality rate was significantly lower in urban than rural areas, and the differences had statistical significance. The annual rates of decline in maternal mortality in Hainan Province and in urban and rural areas from 2003 to 2022 were -5.0% and -3.71%, respectively, showing a negative growth with the decrease rate in rural areas lower than urban areas. The maternal mortality rate in Hainan Province showed a fluctuating downward trend, different from the stable trend of national decrease. The mortality rates for direct obstetric causes of death (233 cases) and indirect obstetric causes of death (230 cases) were 11.59/100 000 and 11.44/100 000, respectively. The results of the maternal mortality review showed a predominance of avoidable deaths (315 cases, 68.03%). Brown's cubic exponential smoothing predicted the maternal mortality rate in Hainan Province for 2023-2025 as 9.45/100 000, 8.17/100 000, and 6.89/100 000. Conclusions　The maternal mortality rate in Hainan Province is largely influenced by maternal deaths in rural areas, and maternal health care in rural areas should be emphasized. Measures such as intervening to address the main factors influencing avoidable maternal deaths, strengthening high-risk maternal management, improving the level of critical maternal care, and providing subsidies for critical maternal care can sustainably reduce the maternal mortality rate in Hainan.

OBJECTIVETo explore the clinical and physical factors that might give rise to radiation-induced esophagitis in three-dimensional conformal radiotherapy for non-small cell lung cancer.

METHODSTo collect the clinical and physical records and follow-up information of 106 NSCLC patients without undergoing surgery in our hospital. χ(2) test, linear tendency test and analysis of variance were employed to analyze the relationship between occurrence of radiation-induced esophagitis and clinical and physical treatment. Logistic analysis was also used for multivariate analysis.

RESULTSAmong the 47 cases of radiation-induced esophagitis, 31 cases were of grade I, 11 of grade II, 5 of grade III, and with a total occurrence rate of 44.3% (47/106). Radiation-induced esophagitis was correlated with Karnofsky scores, radiation sensitization and tumor location (χ(2) = 11.30, 8.45, 7.67, P < 0.05). Radiation-induced esophagitis was correlated with the length of irradiated esophagus and average dose of irradiated esophagus (F = 20.82, 83.08, P < 0.001). With the increase of the irradiated volume percentage from V20, V30, V40 up to V50, the occurrence rate of radiation-induced esophagitis was also increased, almost with a linear trend (P < 0.05). Application of all the above factors to logistic model indicated that radiation sensitization,length of irradiated esophagus, average dose and V50 were all statistically significant foactors in the occurrence of radiation-induced esophagitis (OR = 0.321, 2.850, 7.307 and 8.558, P < 0.05).

CONCLUSIONSRadiation sensitization,length of irradiated esophagus, average dose of irradiated esophagus and V50 are independent factors in the occurrence of radiation-induced esophagitis. V50 is of greater importance in the judgement of occurrence of radiation-induced esophagitis.

Aged ; Carcinoma, Non-Small-Cell Lung ; radiotherapy ; Esophagitis ; etiology ; Esophagus ; pathology ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; radiotherapy ; Male ; Middle Aged ; Multivariate Analysis ; Radiation Injuries ; etiology ; Radiation Tolerance ; Radiotherapy Dosage ; Radiotherapy, Conformal ; adverse effects ; methods ; Retrospective Studies

OBJECTIVETo investigate the expression profile of serum micro (mi)RNAs in cholangiocarcinoma (CCA) and investigate the regulatory contribution of miRNAs to the invasive and metastasis.

METHODSMicroarray analysis was carried out using serum samples collected from 30 patients with CCA, bile duct cancer tissues and the corresponding normal tissues collected from 10 patients, and serum samples from 50 healthy volunteers. The miRNAs identified as dysregulated in CCA were verified by RT-PCR. Focused analysis on miR-224 was carried out using the human CCA cell lines HCCC-9810 and RBE to investigate the role of this miRNA in IL-6 expression (using IL-6 induction), cell growth, invasiveness and metastasis (using miR-224 mimic transfection). The one-way ANOVA test was used for statistical analysis.

RESULTSForty-three miRNAs were dysregulated in CCA (vs. non-CCA, P<0.01), of which 22 were upregulated and 21 were downregulated. RT-PCR data showed that the miR-224 was significantly upregulated in serum as well as in cancer tissue from CCA patients. Induction of HCCC-9810 and RBE cells with IL-6 showed a time-dependent upregulation of miR-224. Furthermore, the HCCC-9810 and RBE cells transfected with miR-224 mimic showed enhanced cell growth, invasiveness and migratory ability.

CONCLUSIONIL-6 may promote the invasive and metastatic properties of CCA through upregulated miR-224. Studies of the differentially expressed serum miRNAs in CCA may help to further elucidate the pathogenic processes of this disease and aid in the development of a novel and effective therapeutic strategy.

Bile Ducts, Intrahepatic ; Cell Line, Tumor ; Cell Proliferation ; Cholangiocarcinoma ; Down-Regulation ; Humans ; Interleukin-6 ; MicroRNAs ; Microarray Analysis ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Transfection ; Up-Regulation

Hereditary spastic paraplegia (HSP) is a group of significantly clinically and genetically heterogeneous neurodegenerative disorders, which are predominantly characterized by progressive lower limbs weakness and spasticity, and spastic paraplegia type 4 (SPG4) is the most common type among them. So far, mutations in 78 distinct loci and 59 mutated genes have been identified in patients with HSP. The protein spastin coded by the SPAST gene plays a critical role in regulating length, number and activity of microtubules, as well as the occurrence and development of various organelles. It is generally believed that the mutated spastin leads to partial or total loss of the function, which is the main pathogenetic mechanism. While recent studies have also suggested that there may exist acquired neurotoxic effects of mutant proteins by the two isoforms (M1, M87) coded by the SPAST gene, which is also one of the critical mechanisms. In this paper, the pathogenesis of SPG4 was reviewed.

Hereditary spastic paraplegia (HSP) is a group of significantly clinically and genetically heterogeneous neurodegenerative disorders, which are predominantly characterized by progressive lower limbs weakness and spasticity inducing gait abnormalities or disorders. In practice, based on the modes of inheritance, it can be divided into autosomal dominant, autosomal recessive, X-linked and mitochondrial maternal inheritance. According to whether the clinical manifestations complicated or not, HSP can be divided into pure and complex form. To date, mutations in 78 distinct loci and 59 mutated gene products have been identified or reported in patients with HSP; among them 20 distinct loci and 13 mutated gene products have been found in autosomal dominant spastic paraplegia. This is a review about the genetic characteristics and research progress of autosomal dominant HSP.

OBJECTIVETo observe the protective effects of safflor Injection (SI) and extract of Ginkgo biloba (EGB) on lung ischemia-reperfusion injury (LIRI) and investigate its mechanism.

METHODSIn vivo rabbit model of LIRI was reconstructed. Forty rabbits were randomly and equally divided into four groups: sham-operation group (sham group), ischemia-reperfusion group (model group), ischemia-reperfusion plus SI group (safflor group) and ischemia-reperfusion plus EGB injection group (EGB group). Malondialdehyde (MDA) content, superoxide dismutase (SOD) and xanthine oxidase (XO) activity in serum were measured. The wet/dry weight ratio (W/D) of the lung tissue and activity of myeloperoxidase (MPO) were also tested. Ultrastructure change of the lung tissue was observed by the electron microscope. The expression of intercellular adhesion molecule-1 (ICAM-1) was measured by immunohistochemistry (IHC).

RESULTSIn the model group, MDA and XO increased and SOD decreased in serum compared with the sham group (P<0.01). The values of W/D, MPO and ICAM-1 of the model group were higher than those of the sham group (P<0.01), but those of the safflor group and EGB group were significantly lower than those of the model group (P<0.01). The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group (P<0.01). Compared with safflor group, in the EGB group MDA, XO, MPO decreased, SOD and ICAM-1 expression increased (P<0.05), but the change of W/D was not statistically significant (P>0.05).

CONCLUSIONSSI and EGB may attenuate LIRI through antioxidation, inhibition of neutrophil aggregation and down-regulation of ICAM-1 expression. But EGB had more effect on the antioxidation, while SI did better on regulating ICAM-1 expression.

Animals ; Female ; Ginkgo biloba ; chemistry ; Immunohistochemistry ; Injections ; Intercellular Adhesion Molecule-1 ; metabolism ; Lung ; blood supply ; pathology ; Male ; Malondialdehyde ; metabolism ; Plant Extracts ; administration & dosage ; pharmacology ; therapeutic use ; Protective Agents ; administration & dosage ; pharmacology ; therapeutic use ; Rabbits ; Reperfusion Injury ; blood ; drug therapy ; Safflower Oil ; administration & dosage ; pharmacology ; therapeutic use ; Superoxide Dismutase ; blood ; Xanthine Oxidase ; blood

OBJECTIVETo explore the effect of electroacupuncture (EA) on the pathomorphology of the sciatic nerve and the role of P2X3 receptors in EA analgesia.

METHODSThe chronic constriction injury (CCI) model was adopted in this study. A total of 32 rats were randomly divided into four groups: sham CCI, CCI, CCI plus contralateral EA (CCI + conEA) and CCI plus ipsilateral EA (CCI + ipsEA). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured. EA began at day 7 after the CCI operation and was applied to the Zusanli (ST 36) and Yanglingquan acupoints (GB 34). At day 14, the pathomorphologic changes of the operated sciatic nerve were demonstrated by hematoxylin and eosin staining. In addition, dorsal root ganglion (DRG) neurons isolated from rats were examined by electrophysiological recording to determine if the P2X3 receptor agonists, adenosine 5'-triphosphate disodium (ATP) and α,β-methylen-ATP (α,β-meATP) evoked inward currents.

RESULTSPain thresholds in the CCI group were obviously decreased post CCI surgery (P<0.01). In the EA groups, thermal and mechanical threshold values were increased after the last EA treatment (P<0.05, P<0.01). There was no significant difference in light microscopic examination among the four groups (P>0.05). Current amplitude after application of ATP and α,β-meATP in DRG neurons were much larger in the CCI group compared to those obtained in sham CCI (P<0.05). ATP and α, β-meATP invoked amplitudes in the CCI + EA groups were reduced. There was no signififi cant difference between the CCI + conEA group and the CCI + ipsEA group (P>0.05).

CONCLUSIONEA analgesia may be mediated by decreasing the response of P2X3 receptors to the agonists ATP and α,β-meATP in the DRG of rats with CCI. No pathological changes of the sciatic nerve of rats were observed after EA treatment.

Adenosine Triphosphate ; analogs & derivatives ; pharmacology ; Animals ; Constriction, Pathologic ; Electroacupuncture ; Ganglia, Spinal ; drug effects ; metabolism ; pathology ; Hyperalgesia ; pathology ; Ion Channel Gating ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Reaction Time ; drug effects ; Receptors, Purinergic P2X3 ; metabolism ; Sciatic Nerve ; injuries ; metabolism ; pathology ; Staining and Labeling

OBJECTIVETo investigate the AvaII polymorphism of low density lipoprotein receptor gene in both health and essential hypertension populations, and to evaluate the association of AvaII polymorphism with level of blood lipid.

METHODSUsing polymerase chain reaction (PCR), AvaII polymorphism was studied in 109 health individuals and 319 patients with essential hypertension.

RESULTSThere were three kinds of genotype: (+/+), (+/-), (-/-). The frequencies of the three genotypes were shown as follows: (+/+) 0.9%, (+/-) 27.5%, (-/-) 71.6% in health population and (+/+) 1.2%, (+/-) 33.9%, (-/-) 64.9% in essential hypertension population, respectively. The frequencies of the two alleles were shown as follows: (+) 14.7%, (-) 85.3% in health population, (+) 18.2%, (-) 81.8% in essential hypertension population and (+) 17.3%, (-) 82.7% in the community, respectively. In male essential hypertension cases, the genotypes were associated with serum TC and LDL-C level in the following order: (-/-) < (+/-) (P < 0.05). In women and healthy population, there was a similar trend but not statistically significant (P > 0.05).

CONCLUSIONSA significant association was found between the common variation of LDL-R gene and serum TC and LDL-C levels. (+) Allele was associated with elevated level of serum TC and LDL-C, but (-) allele was associated with a low level of serum TC and LDL-C. The frequencies of (-) allele in both group were related to serum low level TC while LDL-C was much higher than that reported in the western countries. These data indicated that genetic factors which resistant to hypercholesterolemia in Chinese people were different from those findings in West while might be one of the reasons to explain why that serum TC level in Chinese was lower than people in the western countries.

Adult ; Alleles ; Antihypertensive Agents ; therapeutic use ; China ; epidemiology ; Cholesterol, LDL ; blood ; Community Health Services ; Exons ; Female ; Genotype ; Humans ; Hypertension ; blood ; drug therapy ; epidemiology ; Male ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Receptors, LDL ; genetics ; Triglycerides ; blood

To establish HPLC-MS/MS method for simultaneous determination of 14 toxic or active components in Fuzi formula granules, and further analyze the quality consistency of 29 batches of formula granules by considering the cluster analysis (CA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) and other chemometrics methods. Phenomenonex Gemini C18 column (4.6 mm×150 mm, 5 μm) was used with 0.1% formic acid solution (A) -acetonitrile (B) as the mobile phase. The mass spectrum was scanned by ESI⁺ multiple reaction monitoring (MRM) mode. The contents of aconitine, mesaconitine, hypaconitine, Indaconitine, benzoylaconine, benzoylmesaconine, benzoylhypaconitine, aconine, fuziline, neoline, talatisamine, songorine, higenamine and salsoline were determined. The results showed that 14 compounds had a good linear relationship within their respective concentration range (R²>0.990 0). The limit of quantification was 2.07-7.71 mg·L⁻¹, and the average recovery was 96.07%-102.2%. The content determination results demonstrated that all batches of Fuzi formula granules had very low hypertoxic ingredients and high safety, while the content of active ingredients was greatly different. CA and PCA results showed that there were significant differences in the formula granules between two manufacturers; even though the different batches of samples from the same manufacturer had certain differences, but the difference in manufacturer A was less than that of B. Further PLS-DA showed that the content of cardiotonic substance salsola in the formula granules from manufacturer A was generally higher, while the contents of analgesic and anti-inflammatory substances benzoylmesaconitine and fuziline were generally lower than those in the products from manufacturer B. In conclusion, the safety of Fuzi formula granules was assured well, but the consistency needed to be improved. We recommend that all manufacturers establish strict standard for decoctions in the production process, and form a unified standard method to produce better Fuzi formula granules.