Pathways regulating intestinal stem cells and potential therapeutic targets for radiation enteropathy.

Radiotherapy is a pivotal intervention for cancer patients, significantly impacting their treatment outcomes and survival prospects. Nevertheless, in the course of treating those with abdominal, pelvic, or retroperitoneal malignant tumors, the procedure inadvertently exposes adjacent intestinal tissues to radiation, posing risks of radiation-induced enteropathy upon reaching threshold doses. Stem cells within the intestinal crypts, through their controlled proliferation and differentiation, support the critical functions of the intestinal epithelium, ensuring efficient nutrient absorption while upholding its protective barrier properties. Intestinal stem cells (ISCs) regulation is intricately orchestrated by diverse signaling pathways, among which are the WNT, BMP, NOTCH, EGF, Hippo, Hedgehog and NF-κB, each contributing to the complex control of these cells' behavior. Complementing these pathways are additional regulators such as nutrient metabolic states, and the intestinal microbiota, all of which contribute to the fine-tuning of ISCs behavior in the intestinal crypts. It is the harmonious interplay among these signaling cascades and modulating elements that preserves the homeostasis of intestinal epithelial cells (IECs), thereby ensuring the gut's overall health and function. This review delves into the molecular underpinnings of how stem cells respond in the context of radiation enteropathy, aiming to illuminate potential biological targets for therapeutic intervention. Furthermore, we have compiled a summary of several current treatment methodologies. By unraveling these mechanisms and treatment methods, we aspire to furnish a roadmap for the development of novel therapeutics, advancing our capabilities in mitigating radiation-induced intestinal damage.

A meta-analysis of the value of serum TSH concentration in the diagnosis of differentiated thyroid cancer in patients with thyroid nodules.

Background: In recent years, most studies believe that high TSH level is positively correlated with the incidence of thyroid cancer, but it is still controversial. For this reason, the purpose of this study is to analyze the correlation between preoperative TSH level and thyroid malignant nodules using pathological diagnosis as the gold standard. To evaluate the role of serum TSH in predicting malignancy of thyroid nodules with uncertain cytology.As an important member of the hypothalamus-pituitary-thyroid axis in the endocrine system, TSH plays a crucial role in regulating the growth, differentiation, and function of thyroid cells (Zhang et al., 2023) [1]. Therefore, it has always been considered closely related to TC. Currently, most studies have compared the TSH levels of TC patients and individuals with benign thyroid disease or healthy controls. These findings from various studies indicated that TC patients often demonstrate elevated TSH levels, even when their TSH falls within the normal range. However, it is important to highlight that the current evidence primarily relies on cross-sectional studies, which mainly describe a phenomenon without establishing causal relationships. The involvement of TSH in the early onset or late progression of TC remains unknown, the interaction between TSH and other factors and how it affects TC is not well understood (Gubbi et al., 2020) [2].Symptoms of thyroid cancer are usually insidious, and early thyroid cancer often has no obvious clinical symptoms. Therefore, early detection and early treatment are particularly important, and how to improve the preoperative diagnosis rate of thyroid nodules is also a problem that clinicians pay close attention to. Objective: To evaluate the value of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma in patients with thyroid nodules. Methods: Our study searched databases in both Chinese and English.China Academic Journals FULL-text Database (CNKI), China Online Journals, Chinese Scientific Journals database and Chinese Biomedical Literature Database (CBM) were searched by computer. The English literature was established by PubMed, Embase, Cochrane Library, Web of Science and other databases until June 2022 to search for relevant literatures on the diagnostic test of serum TSH concentration in patients with thyroid nodule. The literatures that met the criteria were screened, the data were extracted, and the literature quality was evaluated. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of the method for the diagnosis of differentiated thyroid carcinoma were calculated and summarized. The receiver operating characteristic (SROC) curve was drawn and the area under the curve was obtained. Results: A total of 23 diagnostic tests were included (5348 lesions). Meta-analysis showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of serum TSH concentration in the diagnosis of differentiated thyroid carcinoma were 0.64, 0.72, 2.511, 0.386 and 7.14, respectively. The area under SROC curve (AUC) was 0.79, and the Q index was 0.7283, indicating no statistically significant difference. Conclusion: Based on current evidence, detection of serum TSH concentration in thyroid nodule patients has high sensitivity and specificity for the diagnosis of differentiated thyroid cancer, which has good clinical application value. However, other auxiliary examinations are still needed to improve the diagnosis rate.

High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

Successful treatment of new-onset diabetes mellitus and IgA nephropathy after COVID-19 vaccination: a case report.

De novo glomerular injuries or relapse of nephropathy following COVID-19 vaccine has been reported. Here we present the first case of successful treatment of new-onset diabetes mellitus and biopsy-proven IgA nephropathy after COVID-19 vaccination. A 56-year-old man with no known medical history of renal dysfunction or diabetes mellitus developed both within 3 months after receiving a third dose of inactivated COVID-19 vaccine (Vero cells). His symptoms were characterized by brown urine, severe dry mouth, and excessive thirst. Randomly acquired blood glucose levels exceeded 33.3 mmol/L. A kidney biopsy showed IgA nephropathy. He was started on insulin for glycemic control. After glucocorticoid and cyclophosphamide treatment, oral tablets of repaglinide, combined with acarbose, controlled blood glucose and stabilized kidney function. This case is unique because the kidneys and pancreas were simultaneously affected by the vaccine. Successful treatment of the disease proved that cyclophosphamide combined with glucocorticoids were effective and that blood glucose was successfully controlled. This treatment option could be useful in similar cases in the future.

Increased retinoic acid signaling decreases lung metastasis in salivary adenoid cystic carcinoma by inhibiting the noncanonical Notch1 pathway.

MYB-NFIB fusion and NOTCH1 mutation are common hallmark genetic events in salivary gland adenoid cystic carcinoma (SACC). However, abnormal expression of MYB and NOTCH1 is also observed in patients without MYB-NFIB fusion and NOTCH1 mutation. Here, we explore in-depth the molecular mechanisms of lung metastasis through single-cell RNA sequencing (scRNA-seq) and exome target capture sequencing in two SACC patients without MYB-NFIB fusion and NOTCH1 mutation. Twenty-five types of cells in primary and metastatic tissues were identified via Seurat clustering and categorized into four main stages ranging from near-normal to cancer-based on the abundance of each cell cluster in normal tissue. In this context, we identified the Notch signaling pathway enrichment in almost all cancer cells; RNA velocity, trajectory, and sub-clustering analyses were performed to deeply investigate cancer progenitor-like cell clusters in primary tumor-associated lung metastases, and signature genes of progenitor-like cells were enriched in the "MYC_TARGETS_V2" gene set. In vitro, we detected the NICD1-MYB-MYC complex by co-immunoprecipitation (Co-IP) and incidentally identified retinoic acid (RA) as an endogenous antagonist of genes in the "MYC_TARGETS_V2" gene set. Following this, we confirmed that all-trans retinoic acid (ATRA) suppresses the lung metastasis of SACC by correcting erroneous cell differentiation mainly caused by aberrant NOTCH1 or MYB expression. Bioinformatic, RNA-seq, and immunohistochemical (IHC) analyses of primary tissues and metastatic lung tissues from patients with SACC suggested that RA system insufficiency partially promotes lung metastasis. These findings imply the value of the RA system in diagnosis and treatment.

In vitro Preparation and Evaluation of Sustained-Release Microcapsules of Salvianolic Acid.

OBJECTIVE: This study aims to investigate the preparation of sustained-release microcapsules of salvianolic acid. METHODS: The stability of salvianolic acid microcapsules was improved, and the time of action was prolonged in the present study. This was prepared using the spray-drying method, with chitosan as the carrier. In the preparation process, the prescription and process were optimized by L9 (34) using an orthogonal design, with yield and drug loading as indexes, in order to obtain optimum conditions. RESULTS: The optimal process and prescription for the preparation of salvianolic acid microcapsules were found to be as follows: mass concentration of chitosan, 1.5%; mass ratio of salvianolic acid to chitosan, 1:3; inlet air temperature, 190°C; and peristaltic pump speed, 300 mL·h-1. The surface of the microcapsules was round, the drug loading was 25.99% ± 2.14%, the yield was 51.88% ± 2.84%, the entrapment efficiency was 86.21% ± 2.89%, and the average particle size was 105.6 ± 2.56 nm. The microcapsules in vitro had certain sustained release characteristics. The internally fitted first-order release model equation was ln(1-Q) = -0.236 t + 4.591 7, r = 0.920. In addition, the results of differential scanning calorimetry show that the properties of salvianolic acid were not changed by the microcapsules. CONCLUSION: Sustained-release microcapsules of salvianolic acid can be successfully prepared by adopting marine polysaccharide as a carrier.

Transcriptome profiling reveals the high incidence of hnRNPA1 exon 8 inclusion in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a malignancy that evolves through a multi-step process. Alternative splicing of several genes has been linked to the progression of the disease, but involvement of alternations in splicing profiles has not been reported. RNA-seq of peripheral blood mononuclear cell (PBMC) samples characterized the differentially expressed and spliced transcripts in five CML chronic phase (CP) and five blast phase (BP) patients, and five healthy controls. Global splicing alteration analysis detected 6474 altered splicing events altered between CML and healthy samples, including many of the previously reported splicing variants and showing a more profound altered splicing deregulation in BP samples. Functional clustering of differentially spliced genes in CP revealed a preferred enrichment relating to cell signaling, while the spliceosome pathway was most overrepresented in BP samples. One differentially spliced spliceosome gene hnRNPA1 showed two splice isoforms; the longer isoform contained exon 8 was preferentially expressed in the BP patients, and the short one excluding exon 8 was specific to healthy controls. Our findings suggested that alternative splicing deregulation played a central role during the progression of CML from CP to BP, and the longer isoform of hnRNPA1 might represent a diagnostic marker and therapeutic target for CML.

The Ras Superfamily of Small GTPases in Non-neoplastic Cerebral Diseases.

The small GTPases from the Ras superfamily play crucial roles in basic cellular processes during practically the entire process of neurodevelopment, including neurogenesis, differentiation, gene expression, membrane and protein traffic, vesicular trafficking, and synaptic plasticity. Small GTPases are key signal transducing enzymes that link extracellular cues to the neuronal responses required for the construction of neuronal networks, as well as for synaptic function and plasticity. Different subfamilies of small GTPases have been linked to a number of non-neoplastic cerebral diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), intellectual disability, epilepsy, drug addiction, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and a large number of idiopathic cerebral diseases. Here, we attempted to make a clearer illustration of the relationship between Ras superfamily GTPases and non-neoplastic cerebral diseases, as well as their roles in the neural system. In future studies, potential treatments for non-neoplastic cerebral diseases which are based on small GTPase related signaling pathways should be explored further. In this paper, we review all the available literature in support of this possibility.

Atorvastatin plus therapeutic ultrasound improve postnatal neovascularization in response to hindlimb ischemia via the PI3K-Akt pathway.

Statins and therapeutic ultrasound (TUS) have been shown to ameliorate angiogenesis on ischemic hindlimb animals and promote human umbilical vein endothelial cells (HUVECs) tube formation and proliferation. Here, we evaluate the therapeutic effect of TUS in combination with atorvastatin (Ator) therapy on angiogenesis in hindlimb ischemia and HUVECs. After subjecting excision of the left femoral artery, all mice were randomly distributed to one of four groups: Control; Ator treated mice (Ator); TUS treated mice (TUS); and Ator plus TUS treated mice (Ator+TUS). At day 14 post-surgery, the Ator plus TUS treatment cohort had the greatest blood perfusion, accompanied by elevated capillary density. In vitro, Ator plus TUS augmented tube formation, migration and proliferative capacities of HUVECs. Additionally, the united administration upregulated expression of angiogenic factors phosphorylated Akt (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor (VEGF), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. Our data indicated that the united administration could significantly enhance ischemia-mediated angiogenesis and exert a protective effect against ischemic/hypoxia induced damage among HUVECs through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway.

Analysis of mitochondrial DNA in Tibetan gastric cancer patients at high altitude.

The highest risk areas of gastric cancer are currently Japan, Korea and China; Qinghai, a high-altitude area, has one of the highest gastric cancer rates in China. The incidence of gastric cancer is higher in the Tibetan ethnic group compared to that in the Han ethnic group in Qinghai. This study was conducted to determine the clinical characteristics of mitochondrial DNA (mtDNA) mutations and copy numbers among Tibetans with gastric cancer residing at high altitudes and investigate the association between adaptations to hypoxic conditions and oncogenesis. A total of 23 Tibetan gastric cancer patients and 40 matched controls were recruited in this study. Leukocyte mtDNA genes and copy numbers were analyzed. The haplogroups were classified based on mitochondrial gene sequences. A total of 56.5% of the study participants had used alcohol at some point in their lives and 73.9% were positive for Helicobacter pylori (H. pylori). Eight mutations in 8 mitochondrial genes were identified in 43.4% of the Tibetan cancer patient group. There were no significant differences in leukocyte mtDNA copy number levels based on smoking status, alchohol consumption, obesity or H. pylori infection between the control and cancer groups. Statistical differences were also not found between gastric cancer patients with and those without mtDNA mutations. The majority of Tibetan patients with gastric cancer belonged to the mitochondrial haplogroup M9. In conclusion, Tibetans with gastric cancer residing at high altitudes exhibited a wide spectrum of mtDNA mutations. However, leukocyte mtDNA copy numbers in stage II gastric cancer were not statistically different compared to those in healthy Tibetans.

Firing pattern modulation through SK channel current increase underlies neuronal survival in an organotypic slice model of Parkinson's disease.

Dopaminergic (DA) neurons in substantia nigra pars compacta (SNc) are vulnerable to excitotoxicity in Parkinson's disease (PD). Neurotoxic stimuli may alter the firing patterns of DA neurons. However, whether firing pattern change underlies neurotoxic stress-induced death of DA neurons remains unknown. In this study, we established long-term cultures of SNc organotypic slices and used this model to evaluate the neurotoxic effects on firing mode and DA neuronal viability following chronic treatment with neurotoxin 6-hydroxydopamine (6-OHDA). Using whole-cell patch clamp to explore the intrinsic membrane properties and firing mode, we showed that chronic exposure to 6-OHDA raised the resting membrane potential of SNc DA neurons and altered their firing pattern, causing it to switch from a regular rhythmic pacemaking firing to an irregular bursting. This firing pattern change correlated with increased death of SNc DA neurons. The 6-OHDA-induced firing pattern change correlated with an increase in the activity of the small conductance calcium-activated potassium channel (SK channel) and with an increase in both the level and activity of protein phosphatase 2A (PP2A). Activation of the SK channel by its agonist 1-EBIO attenuated 6-OHDA-induced firing irregularity and death, while the SK channel antagonist apamin exacerbated the toxic effects of 6-OHDA. Thus, SK channel current is a substantial element in sustaining the SNc DA neuronal rhythmic pacemaking and homeostasis and perturbing SK channel activity underlies 6-OHDA-induced neurotoxicity.

Improved stereotactic procedure enhances the accuracy of deep brain stimulation electrode implantation in non-human primates.

PURPOSE: Non-human primate models of deep brain stimulation (DBS) play an increasingly important role in the exploration of DBS mechanisms. The establishment and recognized usefulness of such models depend on the precise positioning of the stimulating targets and electrode implants. The optimal method of targeting remains controversial. MATERIALS AND METHODS: This paper described an improved stereotactic procedure that uses a self-developed adaptor to improve accuracy. This involved: (1) connecting clinical stereotactic devices with the skull of primates using a self-developed adaptor; (2) pre-operation targeting via magnetic resonance imaging (MRI); (3) target re-checking by microelectrode recording (MER); (4) DBS electrode implantation; (5) post-operative MRI verification of electrode placement and (6) positioning confirmation by DBS programming. RESULTS: Use of the adaptor enabled clinical stereotactic surgery, pre-operative MRI targeting, microelectrode mapping and post-operative verification in primate DBS operations. Discrepancies between achieved and predetermined electrode position were around 0.6 mm. DBS programming improved the motor function of the hemiparkinsonism animals and decreased the numbers of rotation induced by apomorphine, indicating the precise positioning of the stimulating target and successful implanting of electrode using this method. CONCLUSIONS: An improved stereotactic procedure was performed during a non-human primate DBS operation using a self-developed adaptor. The accuracy of DBS electrode implantation in non-human primates was improved with this method.

Long-Term Changes in Drug Craving and Nutritional Status of Opioid Addicts with Nucleus Accumbens Ablative Stereotactic Neurosurgery at Five Years Postoperatively.

BACKGROUND: The nucleus accumbens (NAcc) has been proven to be associated with drug and food craving. NAcc ablative neurosurgery has been suggested to modulate the balance of the brain reward system and thus alleviate drug dependence in patients. It has been hypothesized that it would also alleviate food craving in patients as well as altering their nutritional status. AIMS: This study aimed to estimate the effect of NAcc neurosurgery on drug craving and nutritional status in patients with drug dependence at 5 years postoperatively. METHODS: The study included 100 patients with NAcc surgery and 92 patients without surgery. Body mass index (BMI) and body fat percentage (BF%) were examined to assess nutritional status, and questionnaires were administered to assess drug craving. RESULTS: Compared with the nonsurgery group and the relapse patients from the surgery group, the nonrelapse patients from the surgery group had higher BMI and BF% but lower drug craving. There were no significant differences between the nonsurgery group and the relapse patients in BMI, but the relapse patients had higher drug craving than the nonsurgery group. CONCLUSIONS: Long-term follow-up suggested that NAcc ablative neurosurgery would alleviate drug craving and yield a better nutritional status if individuals sustained abstinence. It would increase drug craving but would not ruin the nutritional status of patients even when individuals relapsed postoperatively.

6-OHDA induced calcium influx through N-type calcium channel alters membrane properties via PKA pathway in substantia nigra pars compacta dopaminergic neurons.

Voltage gated calcium channels (VGCC) are sensitive to oxidative stress, and their activation or inactivation can impact cell death. Although these channels have been extensively studied in expression systems, their role in the brain, particularly in the substantia nigra pars compacta (SNc), remain controversial. In this study, we assessed 6-hydroxydopamine (6-OHDA) induced transformation of firing pattern and functional changes of calcium channels in SNc dopaminergic neurons. Application of 6-OHDA (0.5-2mM) evoked a dose-dependent, desensitizing inward current and intracellular free calcium concentration ([Ca(2+)]i) rise. In voltage clamp, ω-conotoxin-sensitive Ca(2+) current modulation mediated by 6-OHDA reflected an altered sensitivity. Furthermore, we found that 6-OHDA modulated Ca(2+) currents through PKA pathway. These results provided evidence for the potential role of VGCCs and PKA involved in oxidative stress in degeneration of SNc neurons in Parkinson's disease (PD).

Tripartite Motif-Containing 22 Gene -364T/C Polymorphism Associated With Hepatitis B Virus Infection in Chinese Han Population.

BACKGROUND: Hepatitis B virus (HBV) infection significantly contributes to the onset of liver disease and hepatocellular carcinoma. Understanding the pathogenesis of HBV infection susceptibility could help us to control HBV infection effectively. OBJECTIVES: This study investigated single nucleotide polymorphisms (SNPs) of the tripartite motif-containing 22 (TRIM22) gene associated with HBV infection outcome. PATIENTS AND METHODS: A total of 765 Chinese Han subjects were enrolled: 293 patients were presented with chronic hepatitis B (CHB), 224 were asymptomatic HBV carriers, 248 had self-limited HBV infection, and all of them were recruited for TRIM22 SNPs genotyping. RING and SPRY domains of TRIM22 gene were DNA-sequenced, and HBV serum markers and HBV DNA were measured quantitatively in all subjects. RESULTS: 243 (31.76%) of 765 Chinese Han patients showed genetic variation in the TRIM22 gene. TRIM22 SNPs were mainly in RING area -364T/C site, accounting for 98.35% of the population. There were no significant differences (P > 0.05) in the RING domain -364T/C SNP and allele frequencies between patients with chronic hepatitis and asymptomatic HBV carriers. The CC genotype of TRIM22 gene RING domain -364T/C locus (rs10838543) was associated with chronic HBV infection (OR = 2.30, 95% CI = 1.24-3.97, P = 0.0012; OR = 2.26, 95% CI = 1.08-3.74, P = 0.002) and a mutant allele C carrier of the TRIM22 gene was associated with HBV chronic infection (OR = 1.97, 95% CI = 1.10-3.75, P = 0.0049; OR = 2.12, 95% CI = 1.17-3.89, P = 0.0038). CONCLUSIONS: TRIM22 gene RING domain -364T/C polymorphism is associated with chronic HBV infection in Chinese Han population.

Trichuriasis diagnosed by colonoscopy: case report and review of the literature spanning 22 years in mainland China.

Trichuriasis is soil-source parasitic disease, usually endemic in warm, humid, tropical and subtropical countries. We report a case of trichuriasis diagnosed by colonoscopy performed in a non-endemic area and review the literature on the colonoscopic diagnosis of Trichuris trichiura spanning 22 years (1989-2011) in mainland China. A total of 4382 trichuriasis cases were diagnosed by colonoscopy out of 41,337 patients who underwent colonoscopy. Most of the patients were cured by unloading the whipworms using colonoscopy pincers. We strongly suggest colonoscopy as a useful diagnostic and treatment tool, especially when the patient is lightly infected or is infected by only a few male worms with no eggs in the stool. The geographical distribution, parasite burden, and the parasitizing locations of T. trichiura in the intestine of the human body were analyzed, and the clinical signs and symptoms, as well as the utility of colonoscopy in the diagnosis and treatment of trichuriasis are discussed.

Nucleus accumbens surgery for addiction.

BACKGROUND: Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery because of psychological dependence. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. METHODS: Based on animal experiments, our institute started the clinical trial for the treatment of drug addicts' psychological dependence by making lesions in the bilateral NAc with stereotactic surgery from July 2000. RESULTS: The short-term outcomes were encouraging and triggered rapid application of this treatment in China from 2003 to 2004. However, lack of long-term outcomes and controversy eventually led to halting the surgery for addiction by the Ministry of Health of China in November 2004 and a nationwide survey about it later. Our institute had performed this surgery in 272 patients with severe heroin addiction. The follow-up study showed that the 5-year nonrelapse rate was 58% and the quality of life was significantly improved. Patients had several kinds of side effects, but the incidence rate was relatively low. The patients gradually recovered more than 5 years after the surgery. The side effects did not severely influence an individual's life or work. Nationwide surgery showed that the nonrelapse rate was 50% in the sample of 150 cases, from 1167 patients overall who underwent stereotactic surgery in China. CONCLUSIONS: Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location has a significant impact on treatment efficacy and requires further study. Because ablation is irreversible, the NAc surgery for addiction should be performed with cautiousness, and deep brain stimulation (DBS) is an ideal alternative.

Deep brain stimulation of the bilateral nucleus accumbens in normal rhesus monkey.

The nucleus accumbens (NAc) has been considered as a novel target of deep brain stimulation (DBS) for intractable psychiatric disorders. Quite a few questions exist about this new treatment, and might be explored in nonhuman primate models. There are several reports on DBS of brain nucleus other than NAc in nonhuman primates. Therefore, we stereotactically implanted the electrodes into bilateral NAc under the guidance of MRI using a clinical Leksell stereotactic system in normal rhesus monkeys. NAc could be recognized as the area of continuity between the caudate nucleus and putamen in the coronal sections, which is beneath the internal capsule, and the gray matter nucleus between the ventromedial prefrontal cortex and anterior commissure in axial sections, which is medial to the putamen. NAc is mainly at a point 2.0-3.0 mm inferior, 3.0-4.0 mm anterior, and 4.5-5.5 mm lateral to the anterior commissure. The electrodes were implanted accurately and connected to an implantable pulse generator subcutaneously. After recovery from surgery, stimulation with a variety of parameters was trialed, and continuous stimulation at 90 µs, 3.5 V, 160, or 60 Hz was administered individually for 7 days. The behaviors and spontaneous locomotor activity of the animals did not change significantly during stimulation. This is the first report on DBS of NAc in nonhuman primates to the best of our knowledge. Bilateral electrical stimulation of NAc is a safe treatment. This model could be helpful in further studies on the clinical use of NAc stimulation for psychiatric disorders and for a better understanding of the functions of this nucleus.

Associations between personality changes and nucleus accumbens ablation in opioid addicts.

AIM: It has been reported that nucleus accumbens (NAc) lesions can help to prevent relapse in opioid addicts. This article aimed to investigate associations between personality changes and NAc lesions. METHODS: The surgery group consisted of 78 patients who had received bilateral stereotactic lesions of the NAc to treat opioid addiction. Seventy two non-surgery opioid addicts were appropriately paired with the patients of the surgery group as the non-surgery group. All participants were interviewed in person and received urine tests, naloxone provocative tests and hair tests to determine the prevalence of relapse. Eysenck personality questionnaire (EPQ) and the health survey questionnaire (SF-36) were employed to assess personality and functional health, respectively. RESULTS: In the surgery group, 30 participants relapsed, and the non-relapse rate was 61.5% (48/78). Compared with the Chinese normative data, the neuroticism (N) and psychoticism (P) dimensions of the EPQ in the non-surgery group were significantly higher, whereas the lie (L) dimension was significantly lower. There was no significant difference in all dimensions of the EPQ between the surgery group and the Chinese normative data. The N dimension in the relapse group and the L dimension in the surgery group were significantly lower than those of the non-surgery group. The P dimension in the relapse group was significantly higher than that of the non-relapse group. The extraversion (E) dimension was relatively stable between these groups. CONCLUSION: Although the influence of other factors cannot be excluded, it is apparent that surgically induced NAc lesions are associated with lower P and N dimensions for opioid addicts, and a higher P dimension is associated with a tendency to relapse.

Retrospective study of Pneumocystis pneumonia over half a century in mainland China.

A retrospective study was performed on case reports of Pneumocystis pneumonia (PCP) from 1959 to 2009 in mainland China. The epidemiological characteristics of PCP over half a century were investigated over two time spans. The first was from 1959, when the first incidence of PCP was reported, to 1984, before the emergence of AIDS in mainland China. The second was from 1985, when the first AIDS case was reported in mainland China, to the end of 2009. A total of 2351 PCP cases were reported during these two time spans, covering a 51-year period. Only seven PCP cases were reported during the first time span. Six were diagnosed by autopsy, accordingly without treatment, whilst the other was diagnosed by open lung biopsy in a living patient who eventually recovered following treatment with sulfadiazine and pyrimethamine. The other 2344 PCP cases were reported during the second time span (1985-2009) from 21 provinces, four municipalities and three autonomous regions. Among the 2344 PCP cases, 70.22 % (1646/2344) were identified together with human immunodeficiency virus (HIV) infection or were in AIDS patients. The remaining 698 non-HIV-infected patients had undergone organ transplantation, had other underlying diseases such as malignancy or hypoimmunity, or had undetermined diagnosis. The results of statistical analysis indicated that AIDS was the most common underlying disease of PCP for patients <1 year and >14 years. For patients aged between 1 and 14 years, haematological malignancy was the most common underlying disease. The trend of the underlying diseases changed with time, showing that the number of PCP patients afflicted by HIV/AIDS increased dramatically, reaching almost threefold during the most recent 5 years compared with the level of the previous 10 years. The number of patients undergoing organ transplantation or with other underlying diseases rose constantly, but the number of malignancies tended to decline from 1995-2004 to 2005-2009. During the second time span (1995-2009), most of the patients (97.61 %) were diagnosed alive and only 56 cases (2.39 %) were identified by autopsy. The mortality of PCP patients treated with anti-Pneumocystis drugs was 14.61 % for those with HIV/AIDS and 15.84 % for those without HIV/AIDS. For the PCP patients without anti-Pneumocystis treatment, all (100 %) of the HIV/AIDS-associated PCP patients died, whilst 13.79 % (4/29) of non-HIV-infected PCP patients survived. These data from epidemiological investigation of PCP in China over a period of half a century may provide useful information for prevention and the development of treatment of PCP.