[Screening of traditional Chinese medicine-derived snail control drug targets based on network pharmacology].

OBJECTIVE: To screen the targets of traditional Chinese medicine-derived potential plant molluscicides based on network pharmacology and explore the mechanisms of molluscicidal actions. METHODS: The traditional Chinese medicines with molluscicidal actions were screened based on retrospective literature reviews, and their molluscicidal efficiency was summarized. The active ingredients and potential targets of traditional Chinese medicines were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, Unified Protein Database and literature mining using network pharmacology. The drug-active ingredient-target network was created using the software Cytoscape 3.7.2, and the key targets were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using the Metascape software. RESULTS: A total of 27 types of snail control drugs derived from traditional Chinese medicines were screened from publications and classified into 14 categories. Network pharmacology identified 190 active ingredients, and the active ingredients with a high degree in the drug-active ingredient-target network included quercetin, linoleyl acetate, luteolin, beta-carotene, (24S)-ethylcholesta-5,22,25-trans-3beta-ol, fumarine and arctiin, with 181 corresponding potential targets screened. KEGG pathway enrichment analysis revealed that these targets were mainly located in 16 pathways, including the neuroactive ligand-receptor interactions, regulation of adipocyte lipolysis and adrenergic signal in myocardial cells. CONCLUSIONS: This study preliminarily demonstrates the multi-ingredient, multi-target and multi-pathway mechanisms of action of 27 molluscicides. The screened key ingredient may provide the basis for isolation, purification and pharmacological studies of molluscicides, and the screened key targets and key pathways may facilitate the illustration of mechanisms of actions of traditional Chinese medicine-derived molluscicides and development of novel green molluscicides.

Clinical significance of fibrotic, haemostatic and endotoxic changes in patients with liver cirrhosis.

BACKGROUND AND STUDY AIMS: To investigate the relationship among fibrotic, haemostatic and endotoxic changes in patients with different degrees of liver cirrhosis. PATIENTS AND METHODS: Liver fibrotic markers, including hyaluronic acid (HA), Ccollagen IV (Col-IV), laminin (LN), and N-terminal pro-peptide of collagen type III (PIIINP), were determined by radioimmunoassay. A series of haemostatic tests, including prothrombin time (PT), international normalized ratio, activated partial thromboplastin time, antithrombin-III, thrombin time, fibrinogen, fibrin(ogen) degradation product and D-dimer were determined using an automatic coagulation analyszer. Plasma levels of endotoxin were detected quantitatively using an endotoxin detection kit. Correlation analysis of the data was performed. RESULTS: Based on Child-Pugh classification, statistically significant differences in fibrotic markers and haemostatic parameters were found in 249 patients with liver cirrhosis, while no significant differences in endotoxin levels were observed. Based on ascites classification, statistically significant differences in fibrotic markers (such as HA, Col-IV and PIIINP, except for LN) and haemostatic parameters were found. As for endotoxin levels, there were significant differences between the ascites, spontaneous bacterial peritonitis (SBP) and no-ascites groups, while no significant differences were observed between the ascites and SBP groups. Correlation analysis demonstrated some correlation among fibrotic markers, haemostatic parameters and endotoxin. CONCLUSIONS: A close relationship exists between the severity of cirrhosis and fibrotic changes, as well as haemostatic changes. Endotoxin may be an important contributing factor to the development of ascites in cirrhosis. Some correlation may exist between fibrosis, haemostatic and endotoxin.

Nuclear receptor ecdysone-induced protein 75 is required for larval-pupal metamorphosis in the Colorado potato beetle Leptinotarsa decemlineata (Say).

20-hydroxyecdysone (20E) and juvenile hormone (JH) are key regulators of insect development. In this study, three Leptinotarsa decemlineata Ecdysone-induced protein 75 (LdE75) cDNAs (LdE75A, B and C) were cloned from L. decemlineata. The three LdE75 isoforms were highly expressed just before or right after each moult. Within the fourth larval instar, they showed a small rise and a big peak 40 and 80 h after ecdysis. The expression peaks of the three LdE75s coincided with the peaks of circulating 20E levels. In vitro midgut culture and in vivo bioassay revealed that 20E and an ecdysteroid agonist halofenozide (Hal) enhanced LdE75 expression in the day 1 final larval instars. Conversely, a decrease in 20E by feeding a double-stranded RNA (dsRNA) against an ecdysteroidogenesis gene, Shade (LdSHD), repressed the expression of LdE75. Moreover, Hal upregulated the expression of the three LdE75s in LdSHD-silenced larvae. Thus, 20E pulses activate the transcription of LdE75s. Furthermore, ingesting dsE75-1 and dsE75-2 from a common fragment of the three isoforms successfully knocked down these LdE75s, and caused developmental arrest. Finally, knocking down LdE75s significantly repressed the transcription of three ecdysteroidogenesis genes, lowered the 20E titre and affected the expression of two 20E-response genes. Silencing LdE75s also induced the expression of a JH biosynthesis gene, increased JH titre and activated the transcription of a JH early-inducible gene. Thus, Ld E75s are required for larval-pupal metamorphosis and act mainly by modulating 20E and JH titres and mediating their signalling pathways.

Radiation-induced apoptosis of oligodendrocytes and its association with increased ceramide and down-regulated protein kinase B/Akt activity.

PURPOSE: Oligodendrocytes are cells responsible for myelination in the central nervous system and have been shown to undergo radiation-induced apoptosis. The roles of ceramide and protein kinase B/Akt (PKB/Akt) were assessed in radiation-induced apoptosis of oligodendrocytes in vitro. MATERIALS AND METHODS: Primary cultures of oligodendrocytes were established from neonatal rat brains and cell identity was assessed by immunohistochemistry. Apoptosis was assessed histologically according to its specific morphologic features using 4',6-diaminido-2-phenylindole, and by transferase-mediated deoxynucleotidyl transferase nick end-labelling staining. The ceramide level was measured using a diacyglycerol kinase assay, and PKB/Akt activity was determined using immunoblotting and a protein kinase assay. RESULTS: Ionizing radiation, C2-ceramide or wortmannin induced apoptosis in oligodendrocytes but not astrocytes. A rapid increase in ceramide was observed in oligodendrocytes after ionizing radiation. Monensin, an inhibitor of acid sphingomyelinase, reduced the apoptotic response in oligodendrocytes after ionizing radiation. Fumonisin B1, an inhibitor of ceramide synthase, showed no such effect in the cells. Radiation-induced apoptosis of oligodendrocytes was associated with a decrease in PKB activity, similar to that observed after treatment with C2-ceramide or wortmannin, but not after dihydro-C2-ceramide. Confocal microscopy revealed a loss of phosphorylated PKB immunostaining in the nucleus of apoptotic oligodendrocytes after ionizing radiation or C2-ceramide treatment. The level of phosphorylated FKHRL1, a transcription factor phosphorylated by PKB, decreased in irradiated oligodendrocytes. CONCLUSIONS: A ceramide-PKB-mediated signalling pathway might play a role in radiation-induced apoptosis of oligodendrocytes.

Cultural considerations in the assessment and treatment of religious and spiritual problems.

Scott Peck, a psychiatrist who has written several books on the spiritual dimensions of life, including the best-selling The Road Less Traveled, gave an invited address which drew a standing-room only audience at the 1992 Annual Meeting of the American Psychiatric Association. He pronounced that psychiatrists are "ill-equipped" to deal with either religious/spiritual pathology or health. Continuing to neglect religious/spiritual issues, he claimed, would perpetuate the predicaments that are related to psychiatry's traditional neglect of these issues: "occasional, devastating misdiagnosis; not infrequent mistreatment; an increasingly poor reputation; inadequate research and theory; and a limitation of psychiatrists' own personal development." In recent years, there have been a number of developments that have begun to redress psychiatry's cultural insensitivity to the religious and spiritual dimensions of life. In 1990, the APA Committee on Religion and Psychiatry initiated an APA Position Statement entitled "Guidelines Regarding Possible Conflict Between Psychiatrists' Religious Commitments and Psychiatric Practice." These guidelines emphasized that "psychiatrists should maintain respect for their patient's beliefs ... and not impose their own religious, antireligious, or ideologic systems of beliefs on their patients, nor should they substitute such beliefs or ritual for accepted diagnostic concepts or therapeutic practice." These guidelines reinforce the importance of acknowledging and respecting differences in religious/spiritual beliefs between clinicians and their patients. More recently, the Accreditation Council for Graduate Medical Education published the new "Special Requirements for Residency Training in Psychiatry," which incorporated several changes mandating instruction about gender, ethnicity, sexual orientation, and religious/spiritual beliefs. Finally, the inclusion of "religious or spiritual problem" as a diagnostic category for the first time in the DSM-IV acknowledges that religious and spiritual issues can be the focus of psychiatric consultation and treatment. John McIntyre, MD, former APA President, and Harold Pincus, Director of the APA's Office of Research, observed that this new entry in DSM-IV was "a sign of the profession's growing sensitivity not only to religion but to cultural diversity generally." It is hoped that these developments will increase the accuracy of diagnostic assessments, reduce iatrogenic harm from misdiagnosis, and increase the mental health professional's respect for individual beliefs and values.

Religious or spiritual problem. A culturally sensitive diagnostic category in the DSM-IV.

A new diagnostic category entitled religious or spiritual problem has been included in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) under Other Conditions That May Be a Focus of Clinical Attention. Along with several other changes, this category contributes significantly to the greater cultural sensitivity incorporated into DSM-IV. The authors review the approval process, including the changes that were made in both the proposed new category and the former V Code section of DSM-III-R. In addition, the definition, assessment methods, types, and clinical significance of religious and spiritual problems are clarified, along with the differential diagnostic issues raised by the definitional changes in the former V Code section. Finally, clinical issues involving cultural sensitivity and the implications for future research are addressed. The new category could help to promote a new relationship between psychiatry and the fields of religion and spirituality that will benefit both mental health professionals and those who seek their assistance.

Screening for major depression in Vietnamese refugees: a validation and comparison of two instruments in a health screening population.

OBJECTIVES: 1) Using standard cutoffs, to determine the accuracy of two Vietnamese-language depression screening instruments for major depression in a nonpsychiatric setting, 2) to examine the utility of other cutoffs, and 3) to compare the instruments' overall accuracies. DESIGN: 1) A research assistant administered the Vietnamese Depression Scale (VDS) and the Indochinese Hopkins Symptom Checklist Depression Subscale (HSCL-D) to all subjects. 2) The "gold standard" was determined by a native Vietnamese-speaking psychiatrist using a written translation of a standard semistructured clinical interview. SETTING: A health screening clinic at a large public hospital. PATIENTS: A convenience sample of 206 newly arrived adult Vietnamese refugees undergoing routine, mandatory health screening. RESULTS: The psychiatrist diagnosed 7% of the refugees as having major depression. At standard cutoffs, the VDS had a 64% sensitivity, a 98% specificity, a 75% positive predictive value, and a 97% negative predictive value. Corresponding results for the HSCL-D were 86%, 93%, 48%, and 99%. More than half of the patients who had false-positive results had other clinical disorders. For each instrument, adjusting the cutoff improved sensitivity and positive predictive value. Receiver operating characteristic (ROC) curve analysis showed no difference in accuracy between the two instruments. Each instrument took approximately 5-10 minutes to administer. CONCLUSIONS: These instruments accurately identified Vietnamese refugees with major depression and should be of use to clinicians in primary care settings. Standard cutoffs may need to be adjusted in nonpsychiatric settings.

Student education and recruitment into psychiatry : a synergistic proposal.

The authors propose that the most effective recruitment strategy is a strong psychiatric curriculum positioned as a relevant and integral part of undergraduate education for primary care physicians. The necessary ingredients are educational leadership by the chair, a multifaceted curriculum, shared teaching with generalists, and an emphasis on gender and ethnic minority issues. In changing times, it is essential that psychiatric educators remain at the center of the educational stage and continue to attract medical students through sharing the excitement of the intellectual and clinical challenges in psychiatry.

DSM-III-R disorders in Vietnamese refugees. Prevalence and correlates.

This study's purpose was a) to determine the prevalence of DSM-III-R disorders in newly arrived ethnic Vietnamese and ethnic Chinese refugees from Vietnam and b) to determine the correlates of DSM-III-R disorders. A Vietnamese-speaking psychiatrist administered translated sections of the Structured Clinical Interview for DSM-III-R to 201 Vietnamese new arrivals undergoing mandatory health screening. Overall, 18.4% had one or more current disorders: 8.5% had adjustment disorder and 5.5% had major depression. Ethnic Vietnamese, compared with ethnic Chinese, had significantly (p < .05) higher rates of current posttraumatic stress disorder and generalized anxiety disorder. Ethnic differences in psychopathology were largely explained by the fact that ethnic Vietnamese refugees had experienced more traumatic events and separation from family. After adjusting for ethnicity, refugees who reported traumatic events, refugees who were married, and veterans were significantly (p < .05) more likely to have one or more psychiatric disorders.

The ethnic/minority focus unit as a training site in transcultural psychiatry.

The ethnic/minority psychiatric inpatient units (i.e., focus units) at the University of California, San Francisco, train residents in transcultural psychiatry. This article describes the history, goals, and educational program that comprise this unique training experience. Two cases from the Asian Focus Unit illustrate how residents learn trans-cultural psychiatry during interactions with ethnic Asian patients and staff. Educational perspectives and current program evaluation are discussed.

Neuropsychiatric complications of AIDS: a literature review.

Acquired immune deficiency syndrome (AIDS) has become a major public health problem with over 12,000 cases and 6,000 deaths reported to date. Although there has been an explosion of knowledge in the virology, immunology and pathology of AIDS, relatively little has been written on the neuropsychiatric aspects. This report reviews the existing literature on the neuropsychiatric complications of AIDS. As many as 40 percent of patients with AIDS have neurologic complications at some point in their illness. These complications include either focal deficits attributable to opportunistic organisms infecting the CNS or diffuse encephalopathy caused by viral infection or lymphoma infiltration. Psychiatric complications include major depression, adjustment disorder with depressed mood, and organic brain syndrome with affective, delusional or demented features. Inpatient and consulting psychiatrists must be alert to these complications of AIDS so as to make accurate diagnoses and deliver appropriate therapy. Further studies, integrating both psychiatric and neurologic perspectives, are needed to better elucidate the neuropsychiatric complications of AIDS and help plan appropriate therapeutic interventions.