Forensic Analysis of Sudden Death Associated with Sexual Activity / 法医学杂志

OBJECTIVES@#To analyze the characteristics of sudden death associated with sexual activity to provide recommendations for forensic identification.@*METHODS@#A retrospective analysis was conducted on autopsy cases accepted by Forensic Identification Center of Huazhong University of Science and Technology from 1998 to 2018, and a total of 15 cases of sudden death associated with sexual activity were screened out. The general information, case data and pathological changes of 15 cases were collected to find the relationship between sexual activity and sudden death.@*RESULTS@#The ratio of male to female was 1.5∶1. The average age of males was 50.1 years and that of females was 35.0 years. Coronary artery diseases and brain diseases accounted for most of the cases (12/15). Sexual partners were associated with locations of deaths and body dumping behaviors.@*CONCLUSIONS@#Sudden death associated with sexual activity, although rare, may occur in people over 30 years old with pre-existing heart or brain diseases, which should be paid attention to in forensic practice.

Prescription Research and Clinical Application of Wenjingtang / 中国实验方剂学杂志

The prescription research and clinical application of Wenjingtang were summarized in order to provide reference for the formulation of material standard and the development of compound preparation. By systematically sorting out the relevant ancient medical books and modern literature reports， combined with the relevant policy requirements of the development of compound preparations of famous classical formulas， this paper expounded the existing problems and put forward some suggestions. Wenjingtang is composed of nine herbs， which is derived from Complete Effective Prescriptions for Women's Diseases written by CHEN Zi-ming in Song dynasty. The original medicinal plants and medicinal parts of the formula were basically the same as those recorded in the 2020 edition of Chinese Pharmacopoeia， for example， Paeonia lactiflora was the choice of Paeoniae Radix Alba， Cinnamomi Cortex was selected as Guixin， the rhizoma of Curcuma phaeocaulis was selected as Curcumae Rhizoma. It was suggested that raw products should be selected for decoction pieces and processed according to the methods recorded in the 2020 edition of Chinese Pharmacopoeia. According to the dosage of 1 Liang=40 g， the dosages of Angelicae Sinensis Radix， Chuanxiong Rhizoma， Paeoniae Radix Alba， Cinnamomi Cortex， Moutan Cortex and Curcumae Rhizoma were 20 g， the dosages of Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma and Achyranthis Bidentatae Radix were 40 g， the total amount of this formula was 240 g. The 9 kinds of decoction pieces were crushed （particle size<6 mm） separately and mixed， each dose was 20 g， 525 mL of water was added， and then decocted to 280 mL. After filtration， warm medicine was taken for once a day. According to ancient books， Wenjingtang has the functions of activating blood circulation， regulating menstruation，warming meridians and dispersing cold. It is mainly used to treat dysmenorrhea， irregular menstruation and other diseases in modern clinical practice. In addition， it has certain curative effect on endometriosis， pelvic inflammatory disease， acne， eczema and other skin diseases. Through the research， the historical evolution and clinical application of Wenjingtang are fully clarified， which can provide research for the later development and application of this famous classical formula.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

Purpose@#This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. @*Methods@#The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. @*Results@#In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. @*Conclusion@#The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

Nomogram for predicting overall survival in children with neuroblastoma based on SEER database

Purpose@#This study was performed to establish and validate a nomogram for predicting the overall survival in children with neuroblastoma. @*Methods@#The latest clinical data of neuroblastoma in Surveillance, Epidemiology, and End Results (SEER) database was extracted from 2000 to 2016. The cases included were randomly divided into training and validation cohorts. The survival curves were drawn with a Kaplan-Meier estimator to investigate the influences of certain single factors on overall survival. Also, least absolute shrinkage and selection operator regression was applied to further select the prognostic variables for neuroblastoma. Additionally, receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the accuracy of the nomogram. @*Results@#In total, 1,262 patients were collected and 8 independent prognostic factors were achieved, including patients’ age, sex, race, tumor grade, radiotherapy, chemotherapy, tumor site, and tumor size. Then we constructed a nomogram by using the data of the training cohort with 886 cases. Subsequently, the nomogram was validated internally and externally with 886 and 376 cases, respectively. The internal validation revealed that the area under the curves (AUC) of ROC curves of 1-, 3-, and 5-year overall survival were 0.69, 0.78, and 0.81, respectively. Accordingly, the external validation also showed that the AUC of 1-, 3-, and 5-year overall survival were all ≥0.69. Both methods of validation demonstrated that the predictive calibration curves were consistent with standard curves. @*Conclusion@#The nomogram possess the potential to be a new tool in predicting the survival rate of neuroblastoma patients.

Advances in Neuropathologic Research of Hypoglycemic Brain Damage Caused by Insulin Overdose / 法医学杂志

The number of death from insulin overdose, including accidental poisoning, suicide and homicide, is increasing these years. The forensic diagnosis of death from insulin overdose is a tough task. Glucose is the main energy source of the brain. Therefore, hypoglycemic brain damage is considered to be the main reason of death from insulin overdose. Recently, research of hypoglycemic brain damage caused by insulin overdose is gradually being paid attention in the field of forensic medicine. This paper summarizes the neuropathologic changes, pathophysiologic process and potential neural molecular markers of hypoglycemic brain damage caused by insulin overdose in terms of forensic neuropathology, providing reference for the research and practice in forensic medicine related fields.

Trial of Chloroquines in the Treatment of COVID-19 and Its Research Progress in Forensic Toxicology / 法医学杂志

Chloroquines are the long-established prescription drug, which are often used clinically to treat malaria and connective tissue diseases. Since December 2019, corona virus disease 2019 （COVID-19） outbreaks caused by 2019 novel coronavirus （2019-nCoV） has occurred in China and many countries around the world. Due to the lack of drugs against COVID-19, the disease spreads rapidly and the mortality rate is relatively high. Therefore, specific drugs against 2019-nCoV need to be quickly screened. The antimalarial drug chloroquine phosphate which has already been approved is confirmed to have an anti-2019-nCoV effect and has been included in diagnostic and therapeutic guidelines. However, awareness of the risk of chloroquine phosphate causing acute poisoning or even death should be strengthened. The current dosage recommended in clinical treatment is larger than that in previous treatment of malaria and the period of treatment is longer. Many provinces have required close clinical monitoring of adverse reactions. This paper reviews the pharmacological effects, poisoning and toxicological mechanisms, in vivo metabolism and distribution, and forensic issues of chloroquine drugs, in order to provide help to forensic practice and clinical work.

Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft） / 法医学杂志

Autopsy is of great significance to the elucidation of the pathological changes, pathogeneses and causes of death of corona virus disease 2019 （COVID-19） and can provide theoretical basis for more scientific and accurate prevention and control of the outbreak. Based on related laws and regulations, such as the Law of the People's Republic of China on Prevention and Control of Infectious Diseases, the clinical manifestations and epidemiological characteristics of COVID-19, and the related guidelines on the prevention and control of the outbreak, combined with the practical work of forensic pathology examination, the Guide to the Forensic Pathology Practice on Death Cases Related to Corona Virus Disease 2019 （COVID-19） （Trial Draft） has been developed. This guide includes information on the background investigation of the cases, autopsy room requirements, personal prevention and protections, external examinations, autopsy, auxiliary examinations, and so on. This guide can be used as a reference by forensic and pathological examination institutions, as well as examination staff.

Analysis of 4 Cases of Electrocution due to Direct Current Electronic Hunter / 法医学杂志

Objective To summarize the characteristics of cases of electrocution due to direct current （DC） electronic hunter, and to provide references for forensic identification. Methods Four cases of electrocution due to DC electronic hunter were collected. Statistical analysis was carried out from the perspective of the scene and electric marks distribution, damage characteristics and histopathological changes. Results All the 4 cases of electrocution were accidental events. There were multiple electric marks, most of which were located in the lower limbs with serious damage. Some strip type electric marks were visible. Conclusion The distribution, morphological characteristics and severity of the electric marks caused by DC electronic hunter are different from those of the ordinary low-voltage alternating current damage. It is alerting that there would be actions of destroying the scene and abandoning the corpse in such cases.

Functional Investigation of a GRIN2A Variant Associated with Rolandic Epilepsy / 神经科学通报·英文版

N-methyl-D-aspartate receptors (NMDARs), a subtype of glutamate-gated ion channels, play a central role in epileptogenesis. Recent studies have identified an increasing number of GRIN2A (a gene encoding the NMDAR GluN2A subunit) mutations in patients with epilepsy. Phenotypes of GRIN2A mutations include epilepsy-aphasia disorders and other epileptic encephalopathies, which pose challenges in clinical treatment. Here we identified a heterozygous GRIN2A mutation (c.1341T>A, p.N447K) from a boy with Rolandic epilepsy by whole-exome sequencing. The patient became seizure-free with a combination of valproate and lamotrigine. Functional investigation was carried out using recombinant NMDARs containing a GluN2A-N447K mutant that is located in the ligand-binding domain of the GluN2A subunit. Whole-cell current recordings in HEK 293T cells revealed that the N447K mutation increased the NMDAR current density by ~1.2-fold, enhanced the glutamate potency by 2-fold, and reduced the sensitivity to Mg inhibition. These results indicated that N447K is a gain-of-function mutation. Interestingly, alternative substitutions by alanine and glutamic acid at the same residue (N447A and N447E) did not change NMDAR function, suggesting a residual dependence of this mutation in altering NMDAR function. Taken together, this study identified human GluN2A N447K as a novel mutation associated with epilepsy and validated its functional consequences in vitro. Identification of this mutation is also helpful for advancing our understanding of the role of NMDARs in epilepsy and provides new insights for precision therapeutics in epilepsy.

Advance of Forensic Research in Insulin Poisoning / 法医学杂志

Insulin as a common clinical hypoglycemic agent can effectively control serves to lower the concentration of blood glucose. However, insulin overdose can lead to death. In the whole fatal cases of insulin overdose, medical accident is the most common, followed by suicide. Though insulin homicide is extremely rare, it deserves great attention. Though there are some researches about insulin poisoning on forensic toxicology and pathology, it is still a difficult task in forensic practice. In this paper, the mechanism of death, pathological changes, detection methods and diagnose criteria of insulin overdose will be discussed in the view of forensic toxicology and pathology. We hope that this paper could enhance relative knowledges of insulin poisoning for medical examiners.

Routine Hemostasis and Hemogram Parameters: Valuable Assessments for Coagulation Disorder and Chemotherapy in Cancer Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The clotting system abnormalities are the common complication in cancer patients. The aim of this retrospective study was to evaluate the coagulation state, clinical features, and treatment in cancer patients by routine tests.</p><p><b>METHODS</b>A total of 2328 patients with different types of cancer were classified as the positive group (n = 1419, including 53 patients with thrombosis) and the negative group (n = 909) based on D-dimer (DD) value. Of the 2328 cases, 354 were admitted for chemotherapy. Hemostasis test and complete blood count (CBC) were performed during treatment or following-up.</p><p><b>RESULTS</b>This study showed that the hypercoagulable state was affected not only by clinical staging (P < 0.0001) but also by metastasis site (P < 0.0001 for bone vs. lung). Compared to negative DD group, the higher fibrinogen level, the extended activated partial thromboplastin time, and prothrombin time interacted markedly with disease clinical stage (P < 0.05) in the positive group. Between positive DD groups with and without thrombus, the significantly statistic difference in white blood cell (WBC) and DD (P < 0.05) rather than in red blood cell (RBC) and platelet count was observed. However, the higher DD level was not correlated with WBC, RBC, and platelet count in the positive DD group. Furthermore, the hypercoagulable plasma profile in cancer patients was moderated 2-3 weeks after chemotherapy (P < 0.05 for first six cycles).</p><p><b>CONCLUSIONS</b>The routine hemostatic parameters and CBC are valuable to assessment for thrombosis and chemotherapy even for disease prognosis.</p>

Optimization of extraction technology for salidroside, tyrosol, crenulatin and gallic acid in Rhodiolae Crenulatae Radix et Rhizoma with orthogonal test / 中国中药杂志

The extracting technology of salidroside, tyrosol, crenulatin and gallic acid from Rhodiolae Crenulatae Radix et Rhizoma was optimized. With extraction rate of salidroside, tyrosol, crenulatin and gallic acid as indexes, orthogonal test was used to evaluate effect of 4 factors on extracting technology, including concentration of solvent, the dosage of solvent, duration of extraction, and frequency of extraction. The results showed that, the best extracting technology was to extract in 70% alcohol with 8 times the weight of herbal medicine for 2 times, with 3 hours once. High extraction rate of salidroside, tyrosol, crenulatin and gallic acid were obtained with the present technology. The extracting technology was stable and feasible with high extraction rate of four compounds from Rhodiolae Crenulatae Radix et Rhizoma, it was suitable for industrial production.

Anti-complementary phenolic acids from Lonicera japonica / 中国中药杂志

<p><b>OBJECTIVE</b>To study the anti-complementary phenolic acids from Lonicera japonica.</p><p><b>METHOD</b>The anti-complementary activity-directed isolation was carried out with the hemolysis test as guide. All isolation was evaluated for their in vitro anti-complementary activities. The structures were identified by various spectroscopic data including ESI-MS, 1H-NMR, 13C-NMR data.</p><p><b>RESULT</b>Fourteen compounds were isolated from the EtOAc fraction of L. japonica extracts, including 8 phenolic acids: 5-O-caffeoylquinic acid (1), chlorogenic (2), 4-O-caffeoylquinic acid (3), 3,5-di-O-caffeoylquinic acid (4), 4,5-di-O-caffeoylquinic acid (5), 3,4-di-O-caffeoylquinic acid (6), caffeic acid (7) and methyl caffeate acid (8); 3 iridoids: secologanoside (9), sweroside (10) and secoxyloganin (11); and 3 flavonoids: luteolin (12), quercetin (13) and kaempferol (14). Compounds 1-9 and 11-14 showed anti-complementary activity in different extents and 3,5-di-O-caffeoylquinic acid (4) exhibited the most significant activity against the classical pathway.</p><p><b>CONCLUSION</b>Compound 14 is obtained from this plant for the first time, phenolic acids are the main anti-complementary constituents of L. japonica and 3,5-di-O-caffeoylquinic acid(4) is a potential complement inhibitor with strong activity, which worthy to be studied further in the future.</p>

Application of molecularly imprinted technology for separation of PGG from Guizhi Fuling capsule / 中国中药杂志

1,2,3,4,6-penta-O-galloyl-D-glucose (PGG) is one of the main active compounds of Guizhi Fuling capsule. Molecularly imprinted polymers (MIP) have high affinity toward template molecules synthesized by molecularly imprinted technology for its specific combined sites, which can overcome the shortcoming of traditional separation methods, such as complex operation, low efficiency, using large quantity of solvent and environmental pollution. In this paper, surface molecularly imprinted polymer (SMIP) was prepared by surface imprinting with PGG as the template molecule. Its adsorption capacity was measured by the scatchard equation. The separation of PGG from Guizhi Fuling capsule at preparatived scale was achieved with molecularly imprinted polymer as stationary phase and the purity was 90.2% by HPLC. This method can be used to prepare PGG from Guizhi Fuling capsule with large capacity and is easy to operate. It provides a new method for efficient separation and purification for other natural products.

Simultaneously preparation of grams of high purity tyrosol, crenulatin and salidroside from Rhodiola crenulata / 中国中药杂志

Tyrosol, crenulatin and salidroside are the main active constituents of Rhodiola crenulata, with extensive pharmacological activities. In the study, grams of high purity tyrosol, crenulatin and salidroside were simultaneously separated from R. crenulata by the first time. Firstly, R. crenulata was extracted by 70% alcohol. Then, with the yields of three compounds as the index, the macroporous resin was optimized. At last, grams of high purity tyrosol, crenulatin and salidroside were isolated by D-101 macroporousresin, purified by column chromatography. Detected by HPLC, the purity of three compounds were higher than 98%. This method has the advantages of simple process and operation, less dosage of organic solvent, highly yield and reproducibility, suitable for the simultaneously preparation of tyrosol, crenulatin and salidroside.

Preparation of baicalein using thermophilic and sugar-tolerant beta-glucosidase / 中国中药杂志

The reaction conditions of baicalin hydrolyzed into baicalein by a kind of thermophilic and sugar-tolerant beta-glucosidase were studied in this paper. The beta-glucosidase could catalyze baicalin into baicalein well in the acetic acid-sodium acetate buffer. The optimal enzyme activity was at 85 degrees C and pH 5.5. The enzyme was stable at the temperature less than 85 degrees C and pH range of 5-7.5. The maximum reaction rate V. and michaelis constant K. were 0.41 mmol x L(-1) x min(-1) and 3.31 mmol x L(-1) respectively. Different metal ions had different effects on the activity of enzyme. Na+ existing in acetic acid-sodium acetate buffer had an activation effect on enzyme. The enzyme activity was enhanced by the concentrations of glucose below 0.6 mol x L(-1), and was gradually inhibited when monosaccharide concentration was over 0.6 mol x L(-1). When the monosaccharide concentration reached 1.2 mol x L(-1), the inhibition rate of enzyme activity was about 50%, which showed good glucose tolerance. The good reaction conditions through the experiment have been determined as follows, the substrate: enzyme dose was 1 g: 0.2 mL, acetic acid-sodium acetate buffer pH 5.5, reaction temperature 85 degrees C, reaction time 10 h, and the enzymatic hydrolyzation ratio could reach 97%.

Indoor Allergen Levels and Household Distributions in Nine Cities Across China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Chinese allergic subjects have high levels of sensitization to house dust mite (HDM) and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households.</p><p><b>METHODS</b>Dust samples were collected from nine cities. Major allergens Der p 1 and Der f 1 from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.</p><p><b>RESULTS</b>HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from <0.006 to 9.2 µg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.</p><p><b>CONCLUSION</b>HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.</p>

Molecular differences between recombinant coagulation factors and plasma-derived coagulation factors, and their effects on pharmacology and efficacy / 国际药学研究杂志

Since their successful launch, the recombinant coagulation factors have been effective in the treatment and prophylaxis of respective deficiencies, and started to replace plasma-derived coagulation factors. However, immunogenicity and induction of inhibitors associated with the uses of these recombinant products have drawn certain attention. This manuscript reviews the structural differences between several major recombinant coagulation factors and their plasma-derived counteiparts, including sequences and many forms of post-translational modifications, and discusses the possible effects of these structural differences on the pharmacology, efficacy and pharmacokinetics of the products. The demonstration of structural differences and underlying mechanisms helps to improve the production yield and quality of recombinant coagulation factors, which is of significant clinical importance.

Advance in research on chemical constituents from Notopterygii Rhizoma et Radix / 中国中药杂志

This paper summarized the recent 30 years research progress of the chemical constituents from Notopterygii Rhizoma et Radix. The chemical constituents from Notopterygii Rhizoma et Radix mainly consist of coumarins, polyene-polyacetylenes, sesquiterpenes, phenolic acids, while steroids and flavonoids were less reported. All constituents were confirmed and corrected through SciFinder. We also checked the Chinese name and English name and listed the CAS number of each compound. It can provide some guidelines for the research, development and utilization of Notopterygii Rhizoma et Radix in the future. Whether there is columbianin in the Notopterygii Rhizoma et Radix need to be further researched.

Chemical constituents from Artemisia annua / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the chemical constituents of dried whole plants of Artemisia annua.</p><p><b>METHOD</b>The chemical constituents were isolated by repeated silica gel chromatography, medium pressure column chromatography, and semi-preparative HPLC, and their structures were elucidated by spectroscopic analyses and comparison of NMR data with those reported in literature.</p><p><b>RESULT</b>15 compounds were isolated and identified to be 5-O-[(E)-Caffeoyl] quinic acid(l), 1,3-di-O-caffeoylquinic acid(2), 4 5-di-O-caffeoylquinic acid(3), 3, 5-di-O-caffeoylquinic acid (4), 3, 4-di-O-caffeoylquinic acid (5), methyl-3,4-di-O-caffeoylquinic acid(6), methyl-3,5-di-O-caffeoylquinic acid(7), 3,6'-O-diferuloylsucrose(8), 5'-β-D-glucopyranosyloxyjasmonic acid(9), Scopoletin(10), scoparone (11), 4-O-β-D-glucopyranosyl-2-hydroxyl-6-methoxyacetophenone (12), chrysosplenol D (13), casticin (14), chrysosplenetin(15).</p><p><b>CONCLUSION</b>Compounds 2, 6, 8 and 9 are obtained from the Artemisia genus for the first time. Compounds 7 and 15 are obtained from this plant for the first time.</p>