Retrospective Analysis of 291 Cases of Medical Malpractice Involving Death / 法医学杂志

Objective To study the medical malpractice cases involving death, and discuss the identification ideas and methods of medical malpractice cases. Methods A total of 291 medical malpractice cases involving death accepted and settled from January 2012 to December 2017 at the Judicial Appraisal Center of Southern Medical University were collected. Based on the age, gender, hospital level, clinical department, whether or not autopsy was performed, cause of death, cause of medical mistakes, causality and causative potency of the appraised person, statistical analysis was made. Results There were more males than females in medical malpractice cases involving death. Mostly young adults or children were involved in these cases. The number of cases involving tertiary hospitals was the highest; among the clinical departments, the internal medicine department had the largest number of cases, followed by surgery, obstetrics and gynecology, pediatrics, etc. Autopsy rate has a trend of increasing year by year. Most patients die from the natural outcomes of their disease or ineffective treatment. Most hospitals have certain medical mistakes, and have an indirect correlation with the patient's death, mainly slight factors. Conclusion Judicial appraisal of medical malpractice should follow the principle of "one-effect and multi-cause", and comprehensively consider various factors such as, the diseases and constitution of the patient, natural outcomes of the diseases, the current medical technology and the level of diagnosis and treatment of the hospital, etc.

Reactivation of the homeotic tumor suppressor gene CDX2 by 5-aza-2'-deoxycytidine-induced demethylation inhibits cell proliferation and induces caspase-independent apoptosis in gastric cancer cells.

The DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) is widely used as an anticancer drug for the treatment of leukemia and solid tumors. Gastric cancer (GC) patients who were positive for caudal type homeobox transcription factor 2 (CDX2) expression showed a higher survival rate compared with those who were CDX2 negative, which suggests that CDX2 performs a tumor suppressor role. However, the molecular mechanisms leading to the inactivation of CDX2 remain unclear. In the present study we demonstrated that the expression levels of CDX2 and DNA methyltransferase enzyme 1 (DNMT1) mRNA were significantly higher in GC compared with distal non-cancerous tissue. The expression of CDX2 mRNA was significantly correlated with Lauren classification, TNM stage and lymph node metastasis. DNMT1 mRNA expression was significantly correlated with TNM stage, pathological differentiation and lymph node metastasis. The expression of CDX2 mRNA was inversely correlated with that of DNMT1 mRNA in GC. Hypermethylation of the CDX2 gene promoter region, extremely low expression levels of CDX2 mRNA and no expression of CDX2 protein were the characteristics observed in MKN-45 and SGC-7901 GC cell lines. Following the treatment of MKN-45 cells with 5-aza-CdR, the hypermethylated CDX2 gene promoter region was demethylated and expression of CDX2 was upregulated, while DNMT1 expression was downregulated. Furthermore, a concentration- and time-dependent growth inhibition as well as increased apoptosis were observed. Caspase-3, -8 and -9 activities increased in a concentration-dependent manner following exposure to different concentrations of 5-aza-CdR. Therefore, our data show that the overexpression of DNMT1 and methylation of the CDX2 gene promoter region is likely to be responsible for CDX2 silencing in GC. 5-Aza-CdR may effectively induce re-expression of the CDX2 gene, inhibit cell proliferation and enhance the caspase-independent apoptosis of MKN-45 cells in vitro.

Ectopic expression of guanylyl cyclase C and endogenous ligand guanylin correlates significantly with Helicobacter pylori infection in gastric carcinogenesis.

The molecular mechanisms leading to gastric carcinogenesis still remain unclear. Recently, several studies demonstrated that over-expression of guanylyl cyclase C (GCC) has been detected in intestinal-type gastric cancer (GC) and precursor lesions. Our objective was to explore the expression levels of GCC and endogenous ligands guanylin (GN) and uroguanylin (UGN) and the correlation between Helicobacter pylori (H. pylori) and GCC, GN, and UGN expressions in patients at different stages from normal mucosa to superficial gastritis, atrophic gastritis, intestinal metaplasia (IM), dysplasia, and finally adenocarcinoma. The expression of GCC and GN was absent in the distal normal gastric tissues and superficial gastritis in all cases, whereas they were measured in IM, dysplasia, and GC. The expression of GCC and GN was closely related to intestinal-type GC. From superficial gastritis to gastric carcinomas, the H. pylori positive rate was 19.7, 33.3, 69.6, 80.0, and 82.1%, respectively. The positive correlation was found between GCC and GN in IM, dysplasia, and GC. Also, the positive correlation was found between GCC, GN, and H. pylori infection in them. These results demonstrate that the detection of GCC and GN will be beneficial to diagnosis human gastric carcinoma and precancerous lesions. Ectopic expression of GCC and GN in human gastric mucosa and H. pylori infection may play an important role in the carcinogenesis of the intestinal-type GC.

Transfusion of autologous late-outgrowth endothelial cells reduces arterial neointima formation after injury.

AIMS: Late-outgrowth endothelial cells (OECs) exist in blood and other organs. We aimed to explore whether and how OECs participate in re-endothelialization and prevent vascular neointima formation after injury. METHODS AND RESULTS: Rabbit bone marrow OECs were cultured for 4 weeks to increase their numbers. Transfusion of autologous OECs (2 × 106-1 × 107/kg) soon after rabbit ear central artery injury reduced the increase in intima area and the decrease in lumen area observed at days 14 and 28. Transfusion of autologous OECs (1 × 107/kg) ameliorated some early (days 2 and 7) inflammatory and angiogenic responses (local and systemic) to the injury. Red fluorescence was seen within 7 days after transfusion of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labelled acetylated low-density lipoprotein (Dil-acLDL)-incorporated OECs, and 1 h after perfusion of the isolated rabbit ear with Ringer-Locke solution containing Dil-acLDL-incorporated OECs, in the injured rabbit ear central artery. After transfusion of 5-bromo-2'-deoxyuridine (BrdU) incorporated autologous OECs, BrdU-positive cells appeared in the injured artery intima at day 3 and were present in the rescued artery endothelium at day 28. The OECs, ranging from 5%-15% of vascular smooth muscle cells (VSMCs), and the OEC-conditioned medium (5-15%) both inhibited VSMC proliferation and migration in vitro and regulated the arrangement of VSMCs. The VSMCs were helpful for OECs to form tubes in vitro. CONCLUSION: Circulating OECs participate in re-endothelialization directly and inhibit VSMC migration and proliferation by a paracrine pathway; transfusion of large numbers of autologous OECs soon after vascular injury may prevent neointima formation.

Primary investigation of methamphetamine-induced toxicity in PC12 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of methamphetamine (METH)-induced toxicity in PC12 cells.</p><p><b>METHODS</b>PC12 cells were treated with METH for 24 h at the doses of 0, 0.5, 1.0, 1.5, 2.0, or 2.5 mmol/L. The morphological changes of the cells were observed under inverted microscope after the treatment. MTT assay and flow cytometry were used to assess the cell viability and apoptotic rates, respectively, and the level of nitric oxide (NO) was measured by enzyme reduction method.</p><p><b>RESULTS</b>The PC12 cells exposed to METH were morphologically featured by cell shrinkage, dendrite disruption and disappearance of cell reticular formation. METH exposure caused a dose-dependent reduction in the cell viability (P<0.01), resulting in also increased cell apoptotic rate and significant elevation of NO in the cell culture supernatant (P<0.05).</p><p><b>CONCLUSION</b>METH exposure induces cytotoxicity and injury of differentiated PC12 cells, leading to decreased cell viability and increased cell apoptosis and NO level. Cell apoptosis and excessive NO production are involved in METH-induced cytotoxicity.</p>

[Voltage-activated potassium channel blockers inhibit anisodamine-induced relaxation of rabbit aortic smooth muscles precontracted with noradrenaline].

Anisodamine, which is originally extracted from scopolia tangutica and is currently produced in China, is a tropane alkaloid and a muscarinic cholinoceptor blocker. Our previous study found that anisodamine did not alter high K(+)-evoked contraction of rabbit aortic rings using isometric tension recording methods, but could attenuate noradrenaline (NA)-, histamine- or 5-hydroxytryptamine-induced contraction in an endothelium-independent manner. Since the high K(+)-elicited depolarization non-selectively inhibits potassium channels in vascular smooth muscle cell (VSMC) membrane, the vasodilation effect of some potassium channel activators may be inhibited or abolished in high K(+) solution. We hypothesized that some potassium channels in VSMC membrane might play a role in the anisodamine-induced relaxation of blood vessels. The present experiment was designed to investigate whether potassium channel blockers inhibit anisodamine-induced relaxation of the rabbit isolated aortic rings. In a 8-min period, 1, 3 and 10 micromol/L of anisodamine, significantly relaxed the 0.01 micromol/L NA precontracted aortic ring by (19.1+/-3.1)%, (30.1+/-3.8)% and (38.3+/-4.2)%, respectively, compared with the controls [by (4.8+/-2.4)%, (5.1+/-1.8)% and (5.6+/-2.5)%, respectively] (P<0.01). 10 mmol/L of CsCl (a non-selective potassium channel blocker), 1 mmol/L of 4-aminopyridine [a selective voltage-activated potassium channel (K(V)) blocker], 10 mumol/L BaCl2 (a selective inwardly-rectifying potassium channel blocker), 10 micromol/L of glibenclamide (a selective ATP-sensitive potassium channel blocker), 3 micromol/L of charybdotoxin (a large- and intermediate-conductance Ca(2+)-activated potassium channels blocker) and 3 micromol/L of apamin (a selective small conductance Ca(2+)-activated potassium channel blocker) significantly increased the NA-induced contraction by (14.4+/-3.2)%, (16.3+/-5.8)%, (12.7+/-4.2)%, (13.6+/-2.0)%, (11.1+/-5.5)% and (13.4+/-4.3)%, respectively, compared with the control [by (5.6 +/-1.2)%] (P<0.01). In the presence of 10 and 30 mmol/L CsCl or 1 and 3 mmol/L 4-aminopyridine, anisodamine-induced relaxation of the 0.01 micromol/L NA contracted rabbit aortic rings [(28.8+/-3.0)% and (15.9+/-3.7)% or (29.7+/-3.9)% and (19.0+/-5.0)%] significantly deceased, compared with that in the absence of any potassium channel blocker [(38.3+/-4.2)% (P<0.01)] in a 8-min period. However, in the presence of 10, 30 micromol/L of BaCl2, 10, 30 micromol/L of glibenclamide, 3 micromol/L of charybdotoxin, or 3 micromol/L apamin, 10 micromol/L anisodamine-induced relaxation [(37.1+/-3.8)%, (36.2+/-4.7)%, (36.1+/-2.7)%, (35.6+/-3.3)%, (37.8+/-2.0)% and (39.3 +/-4.7) %, respectively] did not decrease, compared with the control [(38.3+/-4.2)%] (P>0.05). This study suggests that K(V) blockers inhibit anisodamine-induced relaxation of the rabbit aortic smooth muscle precontracted with NA and implies that the K(V) in VSMC membrane plays a role in anisodamine-induced relaxation of blood vessels.

Effect of atropine on denervated rabbit ear blood vessels.

Surgical denervation of rabbit ear blood vessel beds was combined with the isolated perfused rabbit ear technique to investigate the mechanism of atropine's vasodilator action. Intramuscular injection of atropine 0.2 mg/kg dilated the denervated blood vessels in the rabbit ear like innervated ones in vivo. Atropine at the maximal concentration (Cmax) of 3 x 10(-6) to 3 x 10(-4) M did not increase effluent flow of the isolated perfused denervated rabbit ear under constant perfusion pressure, but chlorpromazine at a Cmax of 10(-6) M and acetylcholine (ACh) at 2.5 x 10(-7) M significantly increased it and noradrenaline (NA) at 10(-7) M significantly decreased it. Atropine at Cmax of 3 x 10(-7) M did not affect, but at 3 x 10(-6) M it abolished the increase of the effluent flow induced by ACh 2.5 x 10(-7) M. Atropine at 3 x 10(-7) M did not affect it, but at 10(-6), 3 x 10(-6), and 10(-5) it significantly alleviated the decrease of effluent flow induced by NA 10(-7) M. Because the increase of effluent flow of rabbit ear under constant perfusion pressure reflects vasodilation of the ear to some extent, the study suggests that atropine has no direct vasodilator action; its vasodilator action is not attributed to blockade of M-cholinoreceptors located on the vascular wall; however, the alpha1-adrenoceptor might be a target site mediating atropine's vasodilator action in vivo.