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Background: In the past, many data collection systems were in operation for different HIV/AIDS projects in China. We describe the creation of a unified, web-based national HIV/AIDS information system designed to streamline data collection and facilitate data use.Methods: Integration of separate HIV/AIDS data systems was carried out in three phases. Phase 1, from January 2006 to December 2007, involved creating a set of unified data collection forms that took into account existing program needs and the reporting requirements of various international organizations. Phase 2, from January to October 2007, involved creating a web-based platform to host the integrated HIV/AIDS data collection system. Phase 3, from November to December 2007, involved pilot testing the new, integrated system prior to nationwide application.Results: Eight web-based data collection subsystems based on one platform began operation on 1 January 2008. These eight subsystems cover: (i) HIV/AIDS case reporting; (ii) HIV testing and counselling; (iii) antiretroviral treatment (ART) for adults; (iv) ART for children; (v) behavioural interventions for high-risk groups; (vi) methadone maintenance treatment; (vii) sentinel and behavioural surveillance; and (viii) local county background information. The system provides real-time data to monitor HIV testing, prevention and treatment programs across the country.Conclusion: China's new unified, web-based HIV/AIDS information system has improved the efficiency of data collection, reporting, analysis and use, as well as data quality and security. It is a powerful tool to support policy making, program evaluation and implementation of the national HIV/AIDS program and, thus, may serve a model for other countries. [ABSTRACT FROM AUTHOR]

Objective: To assess the overall mortality of methadone maintenance treatment (MMT) clients in China and its associated factors. Methods: A total of 1,511 MMT clients, all of whom enrolled in China's first eight MMT clinics between March and December 2004, were included in this cohort study and followed for approximately six years, until June 2010. Mortality and its predictors were examined using Cox proportional hazards regression models. Results: A total of 154 deaths were observed within 5,391 person-years (PY) of follow-up for an all-cause mortality rate of 28.6 per 1,000 PY. The leading causes of death were drug overdose (33.8%), HIV/AIDS-unrelated disease (21.4%), and HIV/AIDS (16.9%). The all-cause mortality rate of clients engaged in MMT for one year or less was roughly three times that of clients who stayed in MMT for four years or more (14.0 vs. 4.6, p<0.0001), HIV-positive subjects was nearly four times mortality rate than that of HIV-negative individuals (28.1 vs.6.8, p<0.0001). ART-naive HIV-positive subjects had approximately two times higher mortality rate than those receiving ART (31.2 vs. 17.3, <0.0001). After adjusting for confounding variables, we found that being male (HR = 1.63, CI: 1.03–2.57, p = 0.0355) and being HIV-positive (HR = 5.16, CI: 3.70–7.10, p<0.0001) were both associated with higher risk of death whereas increased durations of methadone treatment were associated with a lower risk of death (HR = 0.26, CI: 0.18–0.38, p<0.0001 for two to three years, HR = 0.08, CI: 0.05–0.14, p<0.0001 for four or more years). Conclusion: Overall mortality was high among MMT clients in China. Specific interventions aimed at decreasing mortality among MMT clients are needed. Our study supports the need for keeping client at MMT longer and for expanding ART coverage and suggests the potential benefits of integrated MMT and ART services for drug users in China. [ABSTRACT FROM AUTHOR]

Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson's disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelling evidence that the compensatory expression of synaptotagmin-11 (Syt11) plays a key role in concealing PD-associated phenotypes in parkin knockout (KO) mouse models. Unlike the normal dopamine (DA) release and motor behaviors observed in parkin KO mice, parkin knockdown (KD) in the substantia nigra pars compacta (SNpc) in adult mice led to both the impaired DA release and the pronounced motor deficits. Interestingly, Syt11, a well-established parkin substrate involved in PD, was specifically upregulated in parkin KD mice and in parkin KO mice during the suckling stage, but not in adult parkin KO mice. Importantly, the overexpression of Syt11 alone is capable of inducing PD-like motor and non-motor impairments, as well as the impaired DA release and reuptake, which is essential for parkin-associated pathogenesis of PD. Therefore, this work not only elucidate a compensatory mechanism that accounts for the absence of overt PD phenotypes in parkin KO mice, but also contribute to the comprehensive understanding of the progression of PD, opening new avenues for the therapeutic treatment of PD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Neurotransmitters and neuromodulators can be released via either action potential (AP)-evoked transient or AP-independent continuous neurotransmission. The elevated AP-evoked neurotransmission in the primary sensory neurons plays crucial roles in hyperalgesia. However, whether and how the AP-independent continuous neurotransmission contributes to hyperalgesia remains largely unknown. Here, we show that primary sensory dorsal root ganglion (DRG) neurons exhibit frequent spontaneous microdomain Ca 2+ (smCa) activities independent of APs across the cell bodies and axons, which are mediated by the spontaneous opening of TRPA1 channels and trigger continuous neurotransmission via the cyclic adenosine monophosphate-protein kinase A signaling pathway. More importantly, the frequency of smCa activity and its triggered continuous neurotransmission in DRG neurons increased dramatically in mice experiencing inflammatory pain, inhibition of which alleviates hyperalgesia. Collectively, this work revealed the AP-independent continuous neurotransmission triggered by smCa activities in DRG neurons, which may serve as a unique mechanism underlying the nociceptive sensitization in hyperalgesia and offer a potential target for the treatment of chronic pain., Competing Interests: Competing interests statement:The authors declare no competing interest.

Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and female mice exhibit female preference but shift to male preference when facing survival threats; their preference is mediated by the dimorphic changes in the excitability of ventral tegmental area dopaminergic (VTA DA ) neurons. In males, VTA DA projections to the nucleus accumbens (NAc) mediate female preference, and those to the medial preoptic area mediate male preference. In females, firing-pattern (phasic-like versus tonic-like) alteration of the VTA DA -NAc projection determines sociosexual preferences. These findings define VTA DA neurons as a key node for social decision-making and reveal the sexually dimorphic DA circuit mechanisms underlying sociosexual preference.

Changes in brain tissue stiffness are closely linked to the development and diseases of the nervous system. Endoplasmic reticulum (ER) stress plays a role in various pathological processes related to epilepsy. However, the relationship between stiffness changes, ER stress, and epilepsy remains unclear. This study aimed to investigate the impact of Best1 upregulation on alleviating ER stress and the underlying mechanism. Additionally, we proposed a protective strategy to prevent cell death resulting from ER stress in epilepsy. This study investigated the expression levels of ER stress-related proteins in epileptic tissues of varying stiffness. Atomic force microscopy revealed differences in stiffness across various lesion regions in patients with epilepsy. The expression levels of ECM and ER stress-related proteins were elevated in tissues with higher stiffness. Polypropionamide hydrogels were used to simulate extracellular matrix (ECM) with varying stiffness levels. Basal ER stress increased in the stiffer hydrogel substrates. Furthermore, the calcium-activated anion channel Bestrophin 1 (Best1) mitigated ER stress induced by both the stiffer substrate and thapsigargin. The loss-of-function mutations in Best1 inhibited this activity. The underlying mechanism involves the upregulation of the endosomal sorting complex required for the transport (ESCRT) components by Best1, which helps mitigate ER stress. These findings suggest that increased stiffness of the cellular microenvironment may contribute to neuronal death during epileptogenesis. Additionally, Best1 upregulation may serve as a protective strategy against excessive ER stress-induced neuronal damage in epilepsy., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown. Here by using in vivo and ex vivo models, it is shown that the AP frequency per se modulates DA release through the D2 receptor (D2R), which contributes up to 50% of total DA release. D2R has a voltage-sensing site at D131 and can be deactivated in a frequency-dependent manner by membrane depolarization. This voltage-dependent D2R inhibition of DA release is mediated via the facilitation of voltage-gated Ca 2+ channels (VGCCs). Collectively, this work establishes a novel mechanism that APs per se modulate DA overflow by disinhibiting the voltage-sensitive autoreceptor D2R and thus the facilitation of VGCCs, providing a pivotal pathway and insight into mammalian DA-dependent functions in vivo., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Schizophrenia is a severe neuropsychiatric disease, but the initiation mechanisms are unclear. Although antipsychotics are effective against positive symptoms, therapeutic interventions for negative symptoms are limited due to the lack of pathophysiological mechanisms. Here we identify synaptotagmin-11 (Syt11) as a potential genetic risk factor and dopamine over-transmission as a mechanism in the development of schizophrenia. Syt11 expression is reduced in individuals with schizophrenia but restored following the treatment with antipsychotics. Syt11 deficiency in dopamine neurons in early adolescence, but not in adults, leads to persistent social deficits and other schizophrenia-like behaviors by mediating dopamine over-transmission in mice. Accordingly, dopamine neuron over-excitation before late adolescence induces persistent schizophrenia-associated behavioral deficits, along with the structural and functional alternations in the mPFC. Notably, local intervention of D2R with clinical drugs presynaptically or postsynaptically exhibits both acute and long-lasting therapeutic effects on social deficits in schizophrenia mice models. These findings not only define Syt11 as a risk factor and DA over-transmission as a potential risk factor initiating schizophrenia, but also propose two D2R-targeting strategies for the comprehensive and long-term recovery of schizophrenia-associated social withdrawal., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ovarian steroid cell tumor, not otherwise specified (SCT-NOS), is a rare subtype of sex cord-stromal tumor, characterized by hirsutism and virilization. There are, however, few tumor markers reported in the tumor. The following is a case report. Six years ago, the patient underwent a left adnexectomy after being diagnosed with a yolk sac tumor. Her serum CA72-4 levels were significantly elevated when she was diagnosed with SCT-NOS. She suffered from hirsutism and oligomenorrhea with long menstrual cycles. SCT-NOS was confirmed by her histopathological examination. When the tumor was diagnosed, serum CA72-4 levels were elevated. Following tumor resection, serum CA72-4 levels returned to the average reference interval. Whole-exome sequencing (WES) was utilized to identify ten mutations in MKI67, TICAM1, CHD3, ARID5B, ERBB4, POLD1, FZR1, MTCP1, TBX3, and CLTC genes.

Background: The KCNQ1+KCNE1 (I Ks ) potassium channel plays a crucial role in cardiac adaptation to stress, in which β-adrenergic stimulation phosphorylates the I Ks channel through the cyclic adenosine monophosphate (cAMP)/PKA (protein kinase A) pathway. Phosphorylation increases the channel current and accelerates repolarization to adapt to an increased heart rate. Variants in KCNQ1 can cause long-QT syndrome type 1 (LQT1), and those with defective cAMP effects predispose patients to the highest risk of cardiac arrest and sudden death. However, the molecular connection between I Ks channel phosphorylation and channel function, as well as why high-risk LQT1 mutations lose cAMP sensitivity, remain unclear., Methods: Regular patch clamp and voltage clamp fluorometry techniques were utilized to record pore opening and voltage sensor movement of wild-type and mutant KCNQ1/I Ks channels. The clinical phenotypic penetrance of each LQT1 mutation was analyzed as a metric for assessing their clinical risk. The patient-specific-induced pluripotent stem-cell model was used to test mechanistic findings in physiological conditions., Results: By systematically elucidating mechanisms of a series of LQT1 variants that lack cAMP sensitivity, we identified molecular determinants of I Ks channel regulation by phosphorylation. These key residues are distributed across the N-terminus of KCNQ1 extending to the central pore region of I Ks . We refer to this pattern as the I Ks channel PKA phosphorylation axis. Next, by examining LQT1 variants from clinical databases containing 10 579 LQT1 carriers, we found that the distribution of the most high-penetrance LQT1 variants extends across the I Ks channel PKA phosphorylation axis, demonstrating its clinical relevance. Furthermore, we found that a small molecule, ML277, which binds at the center of the phosphorylation axis, rescues the defective cAMP effects of multiple high-risk LQT1 variants. This finding was then tested in high-risk patient-specific induced pluripotent stem cell-derived cardiomyocytes, where ML277 remarkably alleviates the beating abnormalities., Conclusions: Our findings not only elucidate the molecular mechanism of PKA-dependent I Ks channel phosphorylation but also provide an effective antiarrhythmic strategy for patients with high-risk LQT1 variants., Competing Interests: None.

Endocytosis is a fundamental biological process that couples exocytosis to maintain the homeostasis of the plasma membrane and sustained neurotransmission. Super-resolution microscopy enables optical imaging of exocytosis and endocytosis in live cells and makes an essential contribution to understanding molecular mechanisms of endocytosis in neuronal somata and other types of cells. However, visualization of exo-endocytic events at the single vesicular level in a synapse with optical imaging remains a great challenge to reveal mechanisms governing the synaptic exo-endocytotic coupling. In this protocol, we describe the technical details of stimulated emission depletion (STED) imaging of synaptic endocytosis at the single-vesicle level, from sample preparation and microscopy calibration to data acquisition and analysis., (© 2024. Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences.)

Social memory has been developed in humans and other animals to recognize familiar conspecifics and is essential for their survival and reproduction. Here, we demonstrated that parvalbumin-positive neurons in the sensory thalamic reticular nucleus (sTRN Pvalb ) are necessary and sufficient for mice to memorize conspecifics. sTRN Pvalb neurons receiving glutamatergic projections from the posterior parietal cortex (PPC) transmit individual information by inhibiting the parafascicular thalamic nucleus (PF). Mice in which the PPC CaMKII →sTRN Pvalb →PF circuit was inhibited exhibited a disrupted ability to discriminate familiar conspecifics from novel ones. More strikingly, a subset of sTRN Pvalb neurons with high electrophysiological excitability and complex dendritic arborizations is involved in the above corticothalamic pathway and stores social memory. Single-cell RNA sequencing revealed the biochemical basis of these subset cells as a robust activation of protein synthesis. These findings elucidate that sTRN Pvalb neurons modulate social memory by coordinating a hitherto unknown corticothalamic circuit and inhibitory memory engram., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To assess the difference in survival outcomes between stage IIIC and stages IIIA and IIIB in the 2018 FIGO cervical cancer staging system., Methods: The PubMed, EMBASE, MEDLINE and Web of Science were searched for articles published from November 1, 2018 to January 31, 2023. Articles published in English were considered. The included studies compared the survival outcomes of patients with cervical cancer in FIGO 2018 stage IIIC with those in stages IIIA and IIIB. Studies focused on rare histopathological types were excluded. The statistical analyses were performed using Stata 17 software. The endpoints were overall survival (OS) and progression-free survival (PFS)., Results: Ten retrospective cohort studies were eligible, involving 2113 (6.2%), 9812 (28.6%), 44 (0.1%), 10 171 (29.7%), 11 677 (34.1%) and 445 (1.3%) patients in stage IIIA, IIIB, IIIA&B, IIIC, IIIC1, and IIIC2, respectively. In the OS group, stage IIIC/C1 was significantly associated with superior survival compared with stage IIIA (hazard risk [HR] 0.62, 95% confidence interval [CI] 0.41-0.93, P = 0.022; I 2  = 92.9%) and stage IIIB(A&B) (HR 0.56, 95% CI 0.44-0.71, P < 0.001; I 2  = 94.0%). The FIGO 2018 stage IIIC2 was not associated with an increased mortality risk compared with stage IIIA and stage IIIB(A&B). In the PFS group, the outcome of FIGO 2018 stage IIIC/C1 was similar to stage IIIA (HR 0.66, 95% CI 0.27-1.64, P = 0.371; I 2  = 65.6%), but better than stage IIIB(A&B) (HR 0.75, 95% CI 0.68-0.83, P < 0.001; I 2  = 0.0%). The FIGO 2018 stage IIIC2 has similar PFS outcomes to stage IIIA and stage IIIB(A&B)., Conclusion: Our findings demonstrate that survival outcomes of stage IIIC are no worse than those of stage IIIA and stage IIIB in the 2018 FIGO cervical cancer staging system. In cervical cancer, FIGO 2018 stage IIIC1 has significantly better OS outcomes than stage IIIA and stage IIIB., (© 2023 International Federation of Gynecology and Obstetrics.)

A 10 W super-wideband ultra-low-intensity-noise single-frequency fiber laser (SFFL) at 1 µm is experimentally demonstrated, based on dual gain saturation effects from semiconductors and optical fibers, together with an analog-digital hybrid optoelectronic feedback loop. Three intensity-noise-inhibited units synergistically work, which actualizes a connection of effective bandwidth and enhancement of noise-suppressing amplitude. With the cascade action of the semiconductor optical amplifier and optical fiber amplifier, the laser power is remarkably boosted. Eventually, an SFFL with an output power of 10.8 W and a relative intensity noise (RIN) below -150 dB/Hz at the frequency range over 1 Hz is realized. More meaningfully, within the total frequency range of 10 Hz to 10 GHz exceeding 29 octaves, the RIN is controlled to below -160 dB/Hz, approaching the shot-noise limit (SNL) level. To the best of our knowledge, this is the lowest RIN result of SFFL within such an extensive frequency range, and this is the highest output power of the near-SNL super-wideband SFFL. Furthermore, a linewidth of less than 0.8 kHz, a long-term stable polarization extinction ratio of 20 dB, and an optical signal-to-noise ratio of over 60 dB are obtained simultaneously. This start-of-the-art SFFL has provided a systematic solution for high-power and low-noise light sources, which is competitive for sophisticated applications, such as free-space laser communication, space-based gravitational wave detection, and super-long-distance space coherent velocity measurement and ranging.

Single-frequency fiber lasers (SFFLs), 1083 nm, have been extensively applied in 4 He optical pumping magnetometers (OPMs) for magnetic field detection. However, the sensitivity and accuracy of OPMs are constrained by the frequency stability of SFFLs. Focusing on this concern, the frequency-stabilized performance of the 1083 nm SFFLs is successfully improved by externally tailoring the laser linewidth to match the spectral width of the error signal in saturated absorption spectroscopy. Thereinto, a high-intensity error signal of saturated absorption is generated as a large number of 4 He atoms with a wide range of velocities interacting with the 1083 nm laser. Consequently, the root mean square value of the fluctuating frequency after locking is effectively decreased from 24.6 to 13.6 kHz, which achieves a performance improvement of 44.7%. Such a strategy can provide a technical underpinning for effectuating an absolute frequency stabilization with higher precision based on atomic and molecular absorption spectroscopy techniques.

The central mechanisms underlying pain chronicity remain elusive. Here, we identify a reciprocal neuronal circuit in mice between the anterior cingulate cortex (ACC) and the ventral tegmental area (VTA) that mediates mutual exacerbation between hyperalgesia and allodynia and their emotional consequences and, thereby, the chronicity of neuropathic pain. ACC glutamatergic neurons (ACC Glu ) projecting to the VTA indirectly inhibit dopaminergic neurons (VTA DA ) by activating local GABAergic interneurons (VTA GABA ), and this effect is reinforced after nerve injury. VTA DA neurons in turn project to the ACC and synapse to the initial ACC Glu neurons to convey feedback information from emotional changes. Thus, an ACC Glu -VTA GABA -VTA DA -ACC Glu positive-feedback loop mediates the progression to and maintenance of persistent pain and comorbid anxiodepressive-like behavior. Disruption of this feedback loop relieves hyperalgesia and anxiodepressive-like behavior in a mouse model of neuropathic pain, both acutely and in the long term., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

An ultrafine electro-optical frequency comb (EOFC) with plentiful comb teeth is demonstrated. Adopting a single-frequency fiber laser as a light source, cascade phase modulation based on a sinusoidal signal and a frequency-time transformation (FTT) signal is executed to generate the EOFC with high fineness. Meanwhile, a cyclic fast frequency shifting strategy is introduced to boost the number of comb teeth and the bandwidth of the EOFC. As a result, an EOFC with 12600 comb lines covering a broad bandwidth from -6.3 GHz to 6.3 GHz is established, corresponding to an ultrafine comb space of 1 MHz. Moreover, the power fluctuation of a comb tooth is less than 0.5 dBm. This state-of-the-art EOFC has significant potential in the field of precision spectroscopy.

Objective: The current study investigated the role of positive outcome expectations and reward responsiveness in intention to disclose HIV status to children among women living with HIV in China. The moderating role of reward responsiveness was also explored. Method: A 1-year longitudinal survey was conducted. 269 women living with HIV who had at least one child aged >5 years and had not yet disclosed their HIV status to their oldest child were selected from a larger sample of women living with HIV at baseline, with a total of 261 respondents completing the follow-up survey. Results: After adjusting for significant socio-demographic and medical variables, positive outcome expectations positively predicted mothers' intention to disclose HIV, while reward responsiveness had a negative effect. A moderation effect of reward responsiveness was found, with further analysis showing that reward responsiveness has strengthened the relationship between positive outcome expectations and intention to disclose HIV. Conclusion: Findings support the relevance of positive outcome expectations and reward responsiveness to intention of disclosure among women living with HIV in China., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2023 Wang, Hui, Wang, Wang, Sun, Lau, Wang and Mo.)

As a central part of the mammalian brain, the prefrontal cortex (PFC) has been implicated in regulating cocaine-induced behaviors including compulsive seeking and reinstatement. Although dysfunction of the PFC has been reported in animal and human users with chronic cocaine abuse, less is known about how the PFC is involved in cocaine-induced behaviors. By using two-photon Ca 2+ imaging to simultaneously record tens of intact individual networking neurons in the frontal association cortex (FrA) in awake male mice, here we report that a systematic acute cocaine exposure decreased the FrA neural activity in mice, while the chemogenetic intervention blocked the cocaine-induced locomotor sensitization. The hypoactivity of FrA neurons was critically dependent on both dopamine transporters and dopamine transmission in the ventromedial PFC (vmPFC). Both dopamine D1R and D2R neurons in the vmPFC projected to and innervated FrA neurons, the manipulation of which changed the cocaine-induced hypoactivity of the FrA and locomotor sensitization. Together, this work demonstrates acute cocaine-induced hypoactivity of FrA neurons in awake mice, which defines a cortico-cortical projection bridging dopamine transmission and cocaine sensitization., (© 2023. The Author(s).)

An optimized bidirectional pumping fiber amplifier is demonstrated to achieve low-frequency intensity noise suppression and effective power enhancement simultaneously. Based on the concept analysis of the gain saturation effect, the influence of input signal power and pump power on intensity noise suppression is investigated and optimized systematically. Further combining with the optimization of the pumping configuration to achieve the even-distribution gain, the relative intensity noise (RIN) of 1083 nm single-frequency fiber laser (SFFL) is suppressed with 9.1 dB in the frequency range below 10 kHz. Additionally, the laser power is boosted from 10.97 dBm to 25.02 dBm, and a power instability of ±0.31% is realized. This technology has contributed to simultaneously improving the power and noise performance of the 1083 nm SFFL, which can be applied to a multi-channel helium (He) optically pumping magnetometer. Furthermore, this technique has broken the mindset that power amplification of the conventional fiber amplifiers will inevitably cause the degradation of intensity noise property, and provided a valuable guidance for the development of high-performance SFFLs.

Objective: To investigate whether cystectomy or ablation for endometrioma has less impact on ovarian reserve as evaluated by antral follicle count (AFC) and antimüllerian hormone (AMH) levels., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): Patients with endometriomas undergoing cystectomy or ablation., Intervention(s): All prospective studies comparing cystectomy with ablation for endometrioma in the PubMed, EMBASE, MEDLINE and Web of Science until April 3, 2022 were retrieved and reviewed. Medical treatment used as adjuvant therapy for the surgery was excluded. Two authors assessed eligibility and risk of bias independently. The statistical data were pooled using the Review Manager software., Main Outcome Measure(s): The changes of AMH levels and AFC values in cystectomy group and ablation group, including intergroup comparisons and intragroup comparisons., Result(s): Four randomized clinical trials and 2 prospective cohort studies were eligible for the meta-analysis, with a total of 294 patients. In the intergroup comparisons, preoperative AFC values were similar with low heterogeneity, but postoperative AFC values were significantly lower in cystectomy than ablation (mean differences [MD], -1.33; 95% credible interval, -2.15 to -0.51; I 2 = 57%). In the intragroup comparisons of AFC values, sensitivity analyses showed a significant decrease in cystectomy (MD, -1.93; 95% credible interval, -2.40 to -1.45; I 2 = 0%) at 6-month follow-up, compared with no reduction in ablation. The intragroup comparisons of AMH levels supported negative effects on ovarian reserve of both cystectomy (MD, -1.26; 95% credible interval, -1.64 to -0.88; I 2 = 45%) and ablation (MD, -0.70; 95% credible interval, -1.07 to -0.32; I 2 = 0%)., Conclusion(s): Both ablation and cystectomy have significantly detrimental effects on ovarian reserve as evaluated by AMH, but the ablation causes relatively less damage to ovarian reserve as appraised by AFC., Clinical Trial Registration Number: CRD42020152823;PROSPERO (york.ac.uk)., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The extravasation of leukocytes is a critical step during inflammation that requires the localized opening of the endothelial barrier. This process is initiated by the close interaction of leukocytes with various adhesion molecules such as ICAM-1 on the surface of endothelial cells. Here we reveal that mechanical forces generated by leukocyte-induced clustering of ICAM-1 synergize with fluid shear stress exerted by the flowing blood to increase endothelial plasma membrane tension and to activate the mechanosensitive cation channel PIEZO1. This leads to increases in [Ca2+]i and activation of downstream signaling events including phosphorylation of tyrosine kinases sarcoma (SRC) and protein tyrosine kinase 2 (PYK2), as well as of myosin light chain, resulting in opening of the endothelial barrier. Mice with endothelium-specific Piezo1 deficiency show decreased leukocyte extravasation in different inflammation models. Thus, leukocytes and the hemodynamic microenvironment synergize to mechanically activate endothelial PIEZO1 and subsequent downstream signaling to initiate leukocyte diapedesis., (© 2022 by The American Society of Hematology.)

Exocytosis and endocytosis are tightly coupled. In addition to initiating exocytosis, Ca2+ plays critical roles in exocytosis–endocytosis coupling in neurons and nonneuronal cells. Both positive and negative roles of Ca2+ in endocytosis have been reported; however, Ca2+ inhibition in endocytosis remains debatable with unknown mechanisms. Here, we show that synaptotagmin-1 (Syt1), the primary Ca2+ sensor initiating exocytosis, plays bidirectional and opposite roles in exocytosis–endocytosis coupling by promoting slow, small-sized clathrin-mediated endocytosis but inhibiting fast, large-sized bulk endocytosis. Ca2+-binding ability is required for Syt1 to regulate both types of endocytic pathways, the disruption of which leads to inefficient vesicle recycling under mild stimulation and excessive membrane retrieval following intense stimulation. Ca2+-dependent membrane tubulation may explain the opposite endocytic roles of Syt1 and provides a general membrane-remodeling working model for endocytosis determination. Thus, Syt1 is a primary bidirectional Ca2+ sensor facilitating clathrin-mediated endocytosis but clamping bulk endocytosis, probably by manipulating membrane curvature to ensure both efficient and precise coupling of endocytosis to exocytosis.

Background: Vascular endothelial cells are critical for maintaining blood pressure (BP) by releasing biologically active molecules, such as nitric oxide. A non-endothelial cell resident matricellular protein, COMP (cartilage oligomeric matrix protein), plays a pivotal role in maintaining cardiovascular homeostasis, but little is known about its regulatory effect on BP., Methods: Mice were infused with AngII (angiotensin II; 450 ng/kg per minute) for 3 days via an osmotic minipump, and BP was monitored by a tail-cuff system. Second-order mesenteric arteries were isolated from mice for microvascular tension measurement. Nitric oxide was detected by an electron paramagnetic resonance technique. Small-interfering RNA transfection, co-immunoprecipitation, bioluminescence resonance energy transfer assays, and patch-clamp electrophysiology experiments were used for further detailed mechanism investigation., Results: COMP -/- mice displayed elevated BP and impaired acetylcholine-induced endothelium-dependent relaxation compared with wild-type mice with or without AngII. Inhibition of eNOS (endothelial nitric oxide synthase) abolished the difference in endothelium-dependent relaxation between wild-type and COMP -/- mice. Furthermore, COMP directly interacted with the C-terminus of Piezo1 via its C-terminus and activated the endogenous Piezo1 currents, which induced intracellular Ca 2+ influx, Ca 2+ /calmodulin-dependent protein kinase type II and eNOS activation, and nitric oxide production. The Piezo1 activator, Yoda1, reduced the difference in endothelium-dependent relaxation and BP in wild-type and COMP - /- mice. Moreover, COMP overexpression increased eNOS activation and improved endothelium-dependent relaxation and BP., Conclusions: Our study demonstrated that COMP is a novel Piezo1 regulator that plays a protective role in BP regulation by increasing cellular Ca 2+ influx, eNOS activity, and nitric oxide production.

Introduction: Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is a global health focus in most parts of the world. The World Health Organization (WHO) launched the dual Elimination of Mother-to-Child Transmission (EMTCT) of HIV and syphilis initiative and released global guidance on criteria and processes for validation of the EMTCT in 2014. The purpose of this report was to analyze the key validation indicators of EMTCT of HIV in China from 2011 to 2020 and to provide relevant basis information for the implementation of EMTCT action in China., Methods: The report described the coverage of maternal HIV screening and antiretroviral therapy usage for HIV infected pregnant women and their infants in China using the data from the national information systems of PMTCT of HIV, syphilis, and HBV management from 2011 to 2020., Results: The rates of maternal HIV testing during pregnancy (predelivery and at labor) and predelivery increased from 92.9% (8,730,161/9,398,781) and 53.7% (5,050,569/9,398,781) to 99.9% (11,964,026/11,982,321) and 97.5% (11,679,924/11,982,321), respectively. The MTCT rate reduced from 7.4% to 3.6% between 2011 and 2020., Conclusions: The data from the surveillance systems revealed that there was a marked increase in the coverage of HIV screening of pregnant women and antiretrovirals drugs use for HIV infected pregnant women and their infants in China from 2011 to 2020., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2021.)

5-diphosphoinositol pentakisphosphate (5-IP 7 ) is a signalling metabolite linked to various cellular processes. How extracellular stimuli elicit 5-IP 7 signalling remains unclear. Here we show that 5-IP 7 in β cells mediates parasympathetic stimulation of synaptotagmin-7 (Syt7)-dependent insulin release. Mechanistically, vagal stimulation and activation of muscarinic acetylcholine receptors triggers G αq -PLC-PKC-PKD-dependent signalling and activates IP6K1, the 5-IP 7 synthase. Whereas both 5-IP 7 and its precursor IP 6 compete with PIP 2 for binding to Syt7, Ca 2+ selectively binds 5-IP 7 with high affinity, freeing Syt7 to enable fusion of insulin-containing vesicles with the cell membrane. β-cell-specific IP6K1 deletion diminishes insulin secretion and glucose clearance elicited by muscarinic stimulation, whereas mice carrying a phosphorylation-mimicking, hyperactive IP6K1 mutant display augmented insulin release, congenital hyperinsulinaemia and obesity. These phenotypes are absent in mice lacking Syt7. Our study proposes a new conceptual framework for inositol pyrophosphate physiology in which 5-IP 7 acts as a GPCR second messenger at the interface between peripheral nervous system and metabolic organs, transmitting G q -coupled GPCR stimulation to unclamp Syt7-dependent, and perhaps other, exocytotic events., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Triterpenes are considered the major active components in Centella asiatica (L.) Urb. (C. asiatica), such as asiatic acid, madecassic acid, asiaticoside, madecassoside and asiaticoside B. It is difficult to simultaneously determine five triterpenes because of madecassoside isomers (madecassoside and asiaticoside B), and the great polarity difference between triterpene acid and triterpene glycoside. In this study, a simple high performance liquid chromatography method with isocratic elution employing cyclodextrins (CDs) as the mobile phase additives was developed to determine five triterpenes in C. asiatica. Various factors affecting triterpenes retention in the C18 column, such as the nature of CDs, γ-CD concentration, acetonitrile percentage and temperature, were studied. Experimental results showed that γ-CD, as an effective mobile phase additive, could markedly reduce the retention of triterpenes (especially asiatic acid and madecassic acid), and improve the separation for madecassoside and asiaticoside B. The elution of five triterpenes could be achieved on an ODS C18 column within 30 min using the acetonitrile-0.2% phosphoric acid contained 4.0 mM γ-CD (20:80, v/v) mixture as the mobile phase. The retention modification of triterpenes may be attributed to the formation of the triterpenes-γ-CD inclusion complexes. The optimized method was successfully applied for simultaneous determination of five triterpenes in C. asiatica.

White adipose tissue (WAT) expansion in obesity occurs through enlargement of preexisting adipocytes (hypertrophy) and through formation of new adipocytes (adipogenesis). Adipogenesis results in WAT hyperplasia, smaller adipocytes and a metabolically more favourable form of obesity. How obesogenic WAT hyperplasia is induced remains, however, poorly understood. Here, we show that the mechanosensitive cationic channel Piezo1 mediates diet-induced adipogenesis. Mice lacking Piezo1 in mature adipocytes demonstrated defective differentiation of preadipocyte into mature adipocytes when fed a high fat diet (HFD) resulting in larger adipocytes, increased WAT inflammation and reduced insulin sensitivity. Opening of Piezo1 in mature adipocytes causes the release of the adipogenic fibroblast growth factor 1 (FGF1), which induces adipocyte precursor differentiation through activation of the FGF-receptor-1. These data identify a central feed-back mechanism by which mature adipocytes control adipogenesis during the development of obesity and suggest Piezo1-mediated adipocyte mechano-signalling as a mechanism to modulate obesity and its metabolic consequences.

Action potential-induced vesicular exocytosis is considered exclusively Ca 2+ dependent in Katz's Ca 2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca 2+ -independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains elusive. Here, by combining multiple independent recordings, we report that [1] CiVDS robustly presents in the sympathetic nervous system, including sympathetic superior cervical ganglion neurons and slice adrenal chromaffin cells, [2] uses voltage sensors of Ca 2+ channels (N-type and novel L-type), and [3] contributes to catecholamine release in both homeostatic and fight-or-flight like states; [4] CiVDS-mediated catecholamine release is faster than that of Ca 2+ -dependent secretion at the quantal level and [5] increases Ca 2+ currents and contractility of cardiac myocytes. Together, CiVDS presents in the sympathetic nervous system with potential physiological functions, including cardiac muscle contractility., Competing Interests: The authors declare no conflict of interest.

Previous studies have shown that microRNAs are involved in the pathogenesis of ovarian carcinoma (OC). However, the abnormal expression and function of miR-342-3p have not been reported in OC. Therefore, this research was designed to explore its role in OC. In this study, qRT-PCR assay showed that the expression level of miR-342-3p was reduced in OC tissues and cell lines. Functionally, Transwell assay suggested that overexpression of miR-342-3p suppressed cell migration and invasion in OC. In addition, forkhead box protein Q1 (FOXQ1) was confirmed to be a direct target gene by luciferase activity assay. Furthermore, FOXQ1 was found to be upregulated and function as an oncogene in OC. More importantly, miR-342-3p was negatively correlated with FOXQ1 expression in OC tissues. Furthermore, overexpression of FOXQ1 could partially rescue inhibitory effect of miR-342-3p on cell migration and invasion in OC. In brief, we concluded that miR-342-3p inhibited migration and invasion of OC cells through suppressing FOXQ1 expression.

Co-release of multiple neurotransmitters from secretory vesicles is common in neurons and neuroendocrine cells. However, whether and how the transmitters co-released from a single vesicle are differentially regulated remains unknown. In matrix-containing dense-core vesicles (DCVs) in chromaffin cells, there are two modes of catecholamine (CA) release from a single DCV: quantal and sub-quantal. By combining two microelectrodes to simultaneously record co-release of the native CA and ATP from a DCV, we report that (1) CA and ATP were co-released during a DCV fusion; (2) during kiss-and-run (KAR) fusion, the co-released CA was sub-quantal, whereas the co-released ATP was quantal; and (3) knockdown and knockout of the DCV matrix led to quantal co-release of both CA and ATP even in KAR mode. These findings strongly imply that, in contrast to sub-quantal CA release in chromaffin cells, fast synaptic transmission without transmitter-matrix binding is mediated exclusively via quantal release in neurons., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Dynamin 1 (dyn1) is required for clathrin-mediated endocytosis in most secretory (neuronal and neuroendocrine) cells. There are two modes of Ca 2+ -dependent catecholamine release from single dense-core vesicles: full-quantal (quantal) and subquantal in adrenal chromaffin cells, but their relative occurrences and impacts on total secretion remain unclear. To address this fundamental question in neurotransmission area using both sexes of animals, here we report the following: (1) dyn1-KO increased quantal size (QS, but not vesicle size/content) by ≥250% in dyn1-KO mice; (2) the KO-increased QS was rescued by dyn1 (but not its deficient mutant or dyn2); (3) the ratio of quantal versus subquantal events was increased by KO; (4) following a release event, more protein contents were retained in WT versus KO vesicles; and (5) the fusion pore size ( d p ) was increased from ≤9 to ≥9 nm by KO. Therefore, Ca 2+ -induced exocytosis is generally a subquantal release in sympathetic adrenal chromaffin cells, implying that neurotransmitter release is generally regulated by dynamin in neuronal cells. SIGNIFICANCE STATEMENT Ca 2+ -dependent neurotransmitter release from a single vesicle is the primary event in all neurotransmission, including synaptic/neuroendocrine forms. To determine whether Ca 2+ -dependent vesicular neurotransmitter release is "all-or-none" (quantal), we provide compelling evidence that most Ca 2+ -induced secretory events occur via the subquantal mode in native adrenal chromaffin cells. This subquantal release mode is promoted by dynamin 1, which is universally required for most secretory cells, including neurons and neuroendocrine cells. The present work with dyn1-KO mice further confirms that Ca 2+ -dependent transmitter release is mainly via subquantal mode, suggesting that subquantal release could be also important in other types of cells., (Copyright © 2019 the authors 0270-6474/19/390199-13$15.00/0.)

Action potential induces membrane depolarization and triggers intracellular free Ca 2+ concentration (Ca 2+ )-dependent secretion (CDS) via Ca 2+ influx through voltage-gated Ca 2+ channels. We report a new type of somatic exocytosis triggered by the action potential per se-Ca 2+ -independent but voltage-dependent secretion (CiVDS)-in dorsal root ganglion neurons. Here we uncovered the molecular mechanism of CiVDS, comprising a voltage sensor, fusion machinery, and their linker. Specifically, the voltage-gated N-type Ca 2+ channel (Ca V 2.2) is the voltage sensor triggering CiVDS, the SNARE complex functions as the vesicle fusion machinery, the "synprint" of Ca V 2.2 serves as a linker between the voltage sensor and the fusion machinery, and ATP is a cargo of CiVDS vesicles. Thus, CiVDS releases ATP from the soma while CDS releases glutamate from presynaptic terminals, establishing the Ca V 2.2-SNARE "voltage-gating fusion pore" as a novel pathway co-existing with the canonical "Ca 2+ -gating fusion pore" pathway for neurotransmitter release following action potentials in primary sensory neurons., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Long noncoding RNA activated by transforming growth factor-β (lncRNA-ATB) is a novel lncRNA, which is recently reported to have critical roles in carcinogenesis and progression of several cancers. However, the expression, clinical values, biological roles, and underlying molecular mechanisms of lncRNA-ATB in osteosarcoma are still known. In this study, we measured lncRNA-ATB expression in serum and osteosarcoma tissues of osteosarcoma patients, analyzed its diagnostic and prognostic values. Serum lncRNA-ATB is increased in osteosarcoma patients and could accurately discriminate osteosarcoma patients from healthy controls. LncRNA-ATB is also upregulated in osteosarcoma tissues and cell lines, and positively associated with Enneking stage, metastasis and recurrence. Increased lncRNA-ATB level indicates poor recurrence-free survival and overall survival. Functional experiments demonstrated that overexpression of lncRNA-ATB enhances osteosarcoma cells proliferation, migration, and invasion, and while depletion of lncRNA-ATB inhibits osteosarcoma cells proliferation, migration, and invasion. Mechanistically, we found that lncRNA-ATB inhibits miR-200s, and upregulates miR-200s target genes ZEB1 and ZEB2. Additionally, the roles of lncRNA-ATB on osteosarcoma cells proliferation, migration, and invasion in vitro , and osteosarcoma tumor growth in vivo are dependent on the regulation of miR-200s. Taken together, this study suggests that lncRNA-ATB may be a potential diagnostic and prognostic biomarker and a therapeutic target for osteosarcoma., Competing Interests: None.

Objective: To learn about the effects of psychological counseling intervention on reducing heroin use, increasing methadone dosage and improving compliance rate of methadone maintenance treatment (MMT)., Methods: Subjects who had had at least one positive result for regular urine morphine tests during the past three months were recruited from 16 MMT clinics. During the three-month intervention period, the subjects received regular psychological counseling provided by doctors (once every other week) and peer education (once a week). Positive rates of urine morphine tests, average days receiving MMT during three months before the intervention and during the intervention, and average daily dosage of methadone during the last week before intervention and during the last week of the intervention programs conducted were recorded and compared., Results: A total of 492 patients receiving MMT were surveyed. There were significant changes in positive rates for urine morphine tests, average daily dosage, and average days on MMT before and during the intervention programs. The positive rate for urine morphine tests dropped from 50.1% to 27.1%; the average daily dosage of methadone increased from 63.0 mg to 72.6 mg; the average days receiving MMT increased from 69.4 days to 73.9 days., Conclusion: Intensive psychological counseling intervention was effective in reducing heroin use, increasing methadone dosage and improving compliance rate of MMT among patients receiving MMT.

Objective: To explore the impacts of antiretroviral treatment on drug use and high risk sexual behaviors among HIV-positive MMT clients., Methods: A cross-sectional study was conducted in patients undergoing ART (ART-experienced) and patients not undergoing ART (ART-naive) attending MMT in 5 clinics in Yunnan Honghe and Dehong prefectures in 2014. A questionnaire was designed to collect socio-demographic characteristics, ART and MMT information and sexual and drug use behaviors within 3 months before the investigation was conducted. Logistic regression analysis was conducted to identify the predictors for drug use and risky sexual behaviors., Results: A total of 328 cases were included in the analysis, among which 202 were ART-experienced and 126 were ART-naÏve. Among 152 respondents who were sexually active, 61 (40.1%) reported having unprotected sex (UPS) with their regular partners in the prior 3 months. A total of 57.6% (189/328) of the respondents used drugs in the prior 3 months. Multiple logistic regression analysis revealed that younger than 35 years old (OR = 3.57, 95% CI: 1.23-10.37), fertility desire (OR = 4.47, 95% CI: 1.49-13.41), partner being HIV-positive (OR = 4.62, 95% CI: 1.80-11.86), length of MMT attendance less than 5 years (OR = 2.92, 95% CI: 1.14-7.53), agreed that it was necessary to use condom no matter the viral load is high or low (OR = 0.14, 95% CI: 0.04-0.51) were protective factors of UPS in the prior 3 months. Multiple logistic regression analysis revealed that being Han (OR = 0.46, 95% CI: 0.24-0.89), feeling having good health status (OR = 0.39, 95% CI: 0.18-0.85), being enrolled in ART (OR = 0.32, 95% CI: 0.17-0.60) were protective factors for drug use in the prior three months, having contact with drug using friends (OR = 4.41, 95% CI: 2.31-8.29), having experience of missing an MMT dose (OR = 3.47, 95% CI: 1.92-6.29), and not satisfied with current MMT dose (OR = 13.92, 95% CI: 3.24-59.93) were risk factors for drug use during the prior three months., Conclusion: ART was not associated with risky sexual behavior and drug use in the prior 3 months in this population. Future interventions should promote ART among this population, and provide education at the same time to prevent the emergence of cross infections and drug-resistant strains.

Objective: To understand that whether initiation of antiretroviral therapy (ART) would impact on the change and its reasons regarding the HIV-related high risk behaviors among HIV-positive clients who attending the methadone maintenance treatment (MMT)., Methods: In-depth interviews were conducted among 34 MMT clients in Yunnan province who were under ART. The related contents would include information on general demographic charicteristics, HIV infection,MMT, number of sexual partners before and after ART, sexual behavior and frequency of condom use, drug use, needle sharing, changes in risk behaviors before and after the ART, reasons for high-risk behavior, of the clients., Results: The average age of the interviewees was 38.5 years, and most of them were male (70.6%). The clients under this study all admitted that the frequencies of unsafe sex and needle sharing did not increase after the ART initiation, with the main reasons as increasing HIV related awareness, the use of methadone, high accessibility of free condoms and access to clean needles etc. However, 12 of 34 reported being relapsed and 3 reported inconsistent condom use. The interaction of ART and dosage of methadone were connected to the episodes of relapsing and the ART optimism would result in inconsistent condom use., Conclusion: No evidence supported that the ART initiation would increase the risk behaviors among the HIV-infected MMT clients. However, attention needs to be paid to the new challenges caused by high expectation of ART.

Embryonic stem cell-based therapies exhibit great potential for the treatment of Parkinson's disease (PD) because they can significantly rescue PD-like behaviors. However, whether the transplanted cells themselves release dopamine in vivo remains elusive. We and others have recently induced human embryonic stem cells into primitive neural stem cells (pNSCs) that are self-renewable for massive/transplantable production and can efficiently differentiate into dopamine-like neurons (pNSC-DAn) in culture. Here, we showed that after the striatal transplantation of pNSC-DAn, (i) pNSC-DAn retained tyrosine hydroxylase expression and reduced PD-like asymmetric rotation; (ii) depolarization-evoked dopamine release and reuptake were significantly rescued in the striatum both in vitro (brain slices) and in vivo, as determined jointly by microdialysis-based HPLC and electrochemical carbon fiber electrodes; and (iii) the rescued dopamine was released directly from the grafted pNSC-DAn (and not from injured original cells). Thus, pNSC-DAn grafts release and reuptake dopamine in the striatum in vivo and alleviate PD symptoms in rats, providing proof-of-concept for human clinical translation.

Objective: To describe club-based drug use and to explore the determinants on those HIV-positive methadone maintenance treatment (MMT) clients., Methods: This study was conducted in 5 MMT clinics in Yunnan province and 612 MMT clients who met the survey criteria were recruited for the study. Urine sample was tested as a biological marker to identify if heroin, methamphetamine, methylene-dioxy-methyl-amphetamine, buprenorphine or benzodiazepine had been used., Results: The average age among the 612 clients was 38.9 ± 6.3 years. Among these, 78.9% were males, with the average years of education as 8.0 ± 3.4 years. There were 60.5% clients who had good relationship with their families. 153 (25.0%) clients reported having used club-related drugs in the last 12 months. Results from the urine test showed that the positive rate on morphine was 14.4%, while the positive rate for club-related drugs was 26.6%. Factors as residential area, casual sexual partners, retention on MMT and occasionally use of heroin were associated with urine results on club-related drugs and the prevalence of self-reported club drug use (P < 0.05)., Conclusion: Club-related drug use was common among HIV-positive MMT clients. Inspection and supervision for club-related drugs and the education and intervention programs on related high risk behaviors should be strengthened.

Objective: To explore the routes and factors associated with HIV new infection of heroin addicts who had been attending the methadone maintenance treatment (MMT) program., Methods: A 1 : 1 nested case-control study was implemented with the cases (new HIV infections) and controls (HIV negative) selected from the treatment cohort of China MMT clients. Questionnaire was developed to collect information on demographic characters, behaviours on drug use, sexual behaviour, daily dosage of methadone intake, adherence to MMT, and psychological problems. Univariate analysis and multivariate condition logistic regression were used to identify factors associated with HIV infection., Results: 108 (54 paired) clients on MMT were recruited, with 76 males and 32 females. Among them, 95 were Han Chinese and 13 were minorities, with average time of drug use as 12.1 ± 5.0 years. Among 54 new HIV infections, 33 were infected through sharing needles, 12 were through sexual contact and 9 unidentified. Results from multivariate condition logistic regression indicated that having longer duration of heroin use before on MMT (More than 10 years vs. less than 10 years,OR = 20.9, 95% CI:1.62-269.34, P = 0.02), shared needles in the last 6 months (OR = 276.7, 95%CI:5.65-> 999.99, P < 0.01) were risk factors while better adherence (More than 0.5 vs. less than 0.5,OR = 0.07, 95%CI:0.42-0.87, P = 0.04) and living with families (OR = 0.002, 95% CI:0.001-0.94, P < 0.01) were protective factors., Conclusion: Sharing needles was the main route of HIV new infection among those clients that were on MMT. Factors as having received more support from both family and community, improvement of adherence to MMT, reducing the frequency of injection etc., could reduce the risk of HIV infection among those MMT clients.

Objective: To describe the adherence and related determinants among HIV-positive methadone maintenance treatment(MMT)clients in Dali,Yunnan province from 2005 to 2013., Methods: Cases were selected from the "National MMT Information Management System". The main information included demographic, drug abuse behaviors prior to enrollment, MMT treatment and highly active antiretroviral therapy (HAART). Detailed medication records were collected to calculate the adherence to MMT. Multivariate unconditional logistic regression was conducted to analyze the impact factors of adherence., Results: The MMT adherence rate of 480 subjects is 58.11%. Data from the multivariate unconditional logistic regression indicated that among those HIV-positive MMT clients that on HAART program (OR = 1.52, 95% CI:1.03-2.24), related factors as:having stable job(OR = 1.69, 95% CI:1.11-2.56), having compulsory history prior to enrollment in MMT (OR = 1.78, 95% CI:1.04-3.04) were likely to have higher rate on MMT adherence, whereas clients who showed positive result in the last urine morphine test (OR = 0.38, 95% CI:0.24-0.59) were associated with lower rate on MMT adherence., Conclusion: In order to improve the rate of adherence to MMT among those HIV-positive MMT clients, the coverage of HAART needed to be expanded and new approaches in combining MMT and HAART developed. Education and intervention efforts should be focused on clients who currently were jobless, those with last urine morphine testing as positive or had never received compulsory treatment.

Objective: To study the protective effect of atractylenolide I on immunological liver injury induced by BCG and LPS., Method: Kunming mice were randomly divided into 6 groups: the normal group, the model group, positive control biphenyl group, the atractylenolide I high does group, the atractylenolide I middle dose group and the atractylenolide I low dose group (60, 120, 240 mg x kg(-1)), with 12 mice in each group. Immunological liver injury in mice was induced by BCG and LPS to compared liver index and spleen index and detect content of serum ALT, AST, MDA and GSH-px in serum and NO, iNOS, TNF-alpha in serum and liver homogenate. Liver pathological changes were observed by HE staining., Result: Both of atractylenolide I and biphenyl remarkably decrease the increased live index and spleen index (P < 0.05), improve the histopathological changes in liver and pathological grades of liver tissues and relieve the inflammatory reaction induced by BCG and LPS. They showed a notable effect in improving MDA and GSH-px in serum., Conclusion: Atractylenolide I can obviously protect immunological injury liver a dose-dependent manner within the range of test doses. Its mechanism may be related to release or over expression of inhibitory inflammatory medium such as NO, iNOS and TNF-alpha.

Astrocytes release a variety of signaling molecules including glutamate, D-serine, and ATP in a regulated manner. Although the functions of these molecules, from regulating synaptic transmission to controlling specific behavior, are well documented, the identity of their cellular compartment(s) is still unclear. Here we set out to study vesicular exocytosis and glutamate release in mouse hippocampal astrocytes. We found that small vesicles and lysosomes coexisted in the same freshly isolated or cultured astrocytes. Both small vesicles and lysosome fused with the plasma membrane in the same astrocytes in a Ca(2+)-regulated manner, although small vesicles were exocytosed more efficiently than lysosomes. Blockade of the vesicle glutamate transporter or cleavage of synaptobrevin 2 and cellubrevin (both are vesicle-associated membrane proteins) with a clostridial toxin greatly inhibited glutamate release from astrocytes, while lysosome exocytosis remained intact. Thus, both small vesicles and lysosomes contribute to Ca(2+)-dependent vesicular exocytosis, and small vesicles support glutamate release from astrocytes.

Objective: To investigate the absorption kinetics of atractylenolide I in intestines of rats and the influence of P-glycoprotein (P-gp) on the absorption., Method: The absorption kinetics was investigated using the method of in situ intestine absorption in rats and the samples were determined by HPLC., Result: Atractylenolide I is absorbed quite well at all segments of intestine in rats and no specific absorption was founded in different segment. When the concentration of perfusion solution was increased contrarily the absorption rate constant (Ka) kept at the same level. Compared Ka of three different concentration of perfusion solution with variance analysis method, Ka of atractylenolide I had no significant differences. But the Ka values were significently increased in the presence of P-gp inbibitor, verapamil or digoxin., Conclusion: Atractylenolide I can be classified into high penetrating drug. Passive diffusion dominates the absorptive transport behivior of atractylenolide I. Atractylenolide I can be absorbed in the whole intestinal segments and there is not a preferntial absorption zone in the intestine. The absorption and secretion of atractylenolide I are mediated by the efflux transport system, P-gp.

2-methacryloyloxyethyl phosphorylcholine (MPC) polymer membranes are synthesized as biomaterials of the biomembrane structure. The MPC polymer membranes have excellent biocompatibility and blood compatibility, they can effectively reduce protein adsorption and denaturation and inhibit cell adhesion even when the polymer membranes are in contact with whole blood in the absence of any anticoagulants. So, the MPC polymer membranes are widely used in blood purification, artificial organs, membrane oxygenator, and other field of biomedicine. The paper mainly expounds the research advancement and the application prospect of MPC polymer membranes.