Effects on peripheral and central nervous system of key inflammatory intercellular signalling peptides and proteins in psoriasis.

Psoriasis is a chronic systemic inflammatory cutaneous disease. Where the immune system plays an important role in its pathogenesis, with key inflammatory intercellular signalling peptides and proteins including IL-17 and IL-23. The psychoneurological system also figures prominently in development of psoriasis. There is a high prevalence of comorbidity between psoriasis and mental health disorders such as depression, anxiety and mania. Patients with psoriasis often suffer from pathological pain in the lesions, and their neurological accidents could improve the lesions in innervated areas. The immune system and the psychoneurological system interact closely in the pathogenesis of psoriasis. Patients with psoriasis exhibit abnormal levels of neuropeptides both in circulating and localized lesion, acting as immunomodulators involved in the inflammatory response. Moreover, receptors for inflammatory factors are expressed in both peripheral and central nervous systems (CNSs), suggesting that nervous system can receive and be influenced by signals from immune system. Key inflammatory intercellular signalling peptides and proteins in psoriasis, such as IL-17 and IL-23, can be involved in sensory signalling and may affect synaptic plasticity and the blood-brain barrier of CNS through the circulation. This review provides an overview of the multiple effects on the peripheral and CNS under conditions of systemic inflammation in psoriasis, providing a framework and inspiration for in-depth studies of neuroimmunomodulation in psoriasis.

Molecular design, construction and analgesic mechanism insights into the novel transdermal fusion peptide ANTP-BgNPB.

Toad venom, a traditional Chinese medicine, exhibits remarkable medicinal properties of significant therapeutic value. The peptides present within toad venom possess a wide range of biological functions, yet the neuropeptide B (NPB) and it modification requires further exploration to comprehensively understand its mechanisms of action and potential applications. In this study, a fusion peptide, ANTP-BgNPB, was designed to possess better analgesic properties through the transdermal modification of BgNPB. After optimizing the conditions, the expression of ANTP-BgNPB was successfully induced. The molecular dynamics simulations suggested that the modified protein exhibited improved stability and receptor binding affinity compared to its unmodified form. The analysis of the active site of ANTP-BgNPB and the verification of mutants revealed that GLN3, SER38, and ARG42 were crucial for the protein's recognition and binding with G protein-coupled receptor 7 (GPR7). Moreover, experiments conducted on mice using the hot plate and acetic acid twist body models demonstrated that ANTP-BgNPB was effective in transdermal analgesia. These findings represent significant progress in the development of transdermal delivery medications and could have a significant impact on pain management.

Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Development and validation of the hospice professional coping scale among Chinese nurses.

BACKGROUND: Hospice care professionals often experience trauma patient deaths and multiple patient deaths in a short period of time (more so than other nurses). This repeated exposure to the death process and the death of patients leads to greater psychological pressure on hospice care professionals. But at present, people pay more attention to the feelings and care burden of the family members of dying patients but pay less attention to medical staff. Thus, this study aimed to develop a scale on the burden of care for hospice care providers and assess the coping capacity of hospice professionals. Raising awareness of the psychological burden of hospice professionals. METHODS: Through a literature review, research group discussion, Delphi method and a pre-survey of professional coping skills among nurses, 200 hospice professionals who had received training in hospice care from pilot institutions engaged in or providing hospice care were selected for investigation. Cronbach's α coefficient and split-half reliability were used to test the internal consistency of the scale, and content validity and explore factor analysis (EFA) were used to test the construct validity of the scale. RESULTS: Two rounds of Delphi methods were carried out, and the effective recovery rate was 100%. The expert authority coefficients of the two rounds were 0.838 and 0.833, respectively. The Kendall's W coefficient of experts in the first round was 0.121 ~ 0.200 (P < 0.05), and the Kendall's W coefficient of the second round was 0.115-0.136 (P < 0.05), indicating a good level of expert coordination. The final survey scale for the care burden of hospice professionals included four dimensions-working environment (9 items), professional roles (8 items), clinical nursing (9 items) and psychological burden (7 items)-with a total of 33 items. The total Cronbach's α coefficient of the scale was 0.963, and the Cronbach's α coefficients of the working environment, professional roles, clinical nursing and psychological burden dimensions were 0.920, 0.889, 0.936 and 0.910, respectively. The total split-half reliability of the scale was 0.927, and the split-half reliability of each dimension was 0.846, 0.817, 0.891, and 0.832. The content validity of the scale items ranged from 0.90 to 1.00. Exploratory factor analysis revealed 5 common factors, with a total cumulative contribution rate of 68.878%. The common degree of each item in the scale was > 0.4, and the factor loading of each item was also > 0.4. CONCLUSION: The scale is an open-access, short, easy-to-administer scale. And which for assessing hospice care burden among hospice professionals developed in this study demonstrated strong reliability and validity. This tool can serve as a dependable instrument for evaluating the burden of hospice care for terminally ill patients by professionals in the hospice setting.

Growth differentiation factor 15 is required for triple-negative breast cancer cell growth and chemoresistance.

Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine, which is involved in the cellular stress response following acute damage. However, the functional role of GDF15 in triple-negative breast cancer (TNBC) has not been fully elucidated. ELISA, Western blot, and PCR assays as well as bioinformatics analyses were conducted to observe the expression of GDF15. Cell Counting Kit-8, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet staining assays were conducted to evaluate paclitaxel resistance and cell viability. Cell apoptosis was analyzed by Western blotting. Murine xenograft model assay was employed to evaluate tumor growth in vivo . Our data indicate that GDF15 is markedly elevated in paclitaxel-resistant TNBC cells, which is significantly associated with unfavorable prognosis. Silencing of GDF15 robustly inhibits the proliferation of tumor cells and increases their sensitivity to paclitaxel in vitro and in vivo , whereas the treatment of purified GDF15 protein confers breast cancer cells with chemoresistance ability. Moreover, GDF15 activates protein kinase B (AKT) /mammalian target of rapamycin (mTOR) signaling, inhibition of AKT or mTOR reverses the prosurvival effect of GDF15 and enhances the antitumor efficacy of paclitaxel in TNBC cells. Altogether, our study uncovers the role of GDF15 in tumor growth and paclitaxel resistance, implicating a potential therapeutic target for TNBC.

A rare class A carbapenemase FRI-11 in Enterobacter clinical strain.

We found a carbapenem-resistant Enterobacter clinical strain which was susceptible to cefotaxime and ceftazidime. This unusual susceptibility profile promoted the investigation. This strain had blaFRI-11, a rare carbapenemase-encoding gene, on a 93,864-bp plasmid containing two replicons of IncFII(pECLA) and IncFIA(HI1). FRI-11, FRI-2, FRI-3, FRI-4, FRI-6, FRI-7, and FRI-9 belong to the same group of FRI ß-lactamases based on the amino acid sequence similarity and their encoding genes are carried by plasmids containing an IncFII(pECLA) replicon. Awareness should be raised towards FRI carbapenemases that are plasmid-encoded and confer an unusual carbapenem-resistant but 3rd-generation-cephalosporin-susceptible resistance profile.

Enterobacter pseudoroggenkampii sp. nov. carrying quinolone-resistant gene qnrE recovered from clinical samples in China.

Two Enterobacter strains 155092T and 170,225 were isolated from clinical samples, pus and sputum, from two hospitalised patients separately, in China. Preliminary identification using Vitek II microbiology system assigned the strains to the Enterobacter cloacae complex. The two strains were subjected to genome sequencing and genome-based taxonomy analysis with type strains of all Enterobacter species and those within closely related genera Huaxiibacter, Leclercia, Lelliottia, and Pseudoenterobacter. The average nucleotide identity (ANI) and in silico DNA-DNA hybridisation (isDDH) values between the two strains were 98.35% and 89.4%, respectively, suggesting that they belong to one species. The two strains had the highest ANI (95.02% and 95.04%) with the type strain of Enterobacter quasiroggenkampii. Their highest isDDH values, also seen with the type strain of E. quasiroggenkampii, were 59.5% and 59.8%, well below the 70% cutoff to define species. The two strains were also characterised for morphological and biochemical features by a set of experiments and observations. The abilities of metabolising gelatin and L-rhamnose could differentiate the two strains from all currently known Enterobacter species. Collectively, the two strains represent a novel Enterobacter species, for which we propose Enterobacter pseudoroggenkampii sp. nov. as the species name. The type strain of this novel species is155092T (= GDMCC 1.3415T = JCM 35646T). The two strains also carried multiple virulence factors comprising aerobactin-encoding iucABCD-iutA and salmochelin-encoding iroN. The two strains also had chromosomally located qnrE, a gene associated with reduced susceptibility to quinolones, suggesting that this species is a potential reservoir of qnrE genes.

Divergence and integration of identification methods for geriatric mental health disorders in nonspecialized institutions-a qualitative study of service providers from different departments in Shanghai, China.

OBJECTIVES: Global epidemiological evidence indicates high rates of mental illness but low rates of diagnosis among older people. In China, service providers identify older adults with mental disorders in varied ways. Taking Shanghai as an example, this study revealed how the identification methods of geriatric mental health disorders in nonspecialized institutions diverge, providing a reference for the integration of services. METHODS: A purposive sampling method was adopted to conduct semi-structured interviews with 24 service providers from various nonspecialized geriatric mental health care institutions. Interview audio was recorded with consent and converted into verbatim transcripts. The interview data were analysed thematically. RESULTS: Although service providers from the health care system tended to apply a biomedical-oriented assessment, those from the social care system typically identified mental disorders among older people based on selective attention and interpersonal relationships. Although there are stark differences, the various identification mechanisms implicitly converge-the relationship with clients has become an important consideration. CONCLUSION: Geriatric mental health issues urgently require the integration of formal and informal care resources. Referring to the idea of task transfer, social identification mechanisms are expected to be a useful supplement to traditional biomedical-oriented identification.

Huaxiibacter chinensis gen. nov., sp. nov., recovered from human sputum.

Strain 155047T was recovered from human sputum in China in 2021. Preliminary species identification based on limited phenotypic tests assigned the strain to the genus Enterobacter of the family Enterobacteriaceae. The genome sequence of the strain was obtained and had ≤84.43 % average nucleotide identity (ANI) and ≤26.3 % in silico DNA-DNA hybridization (isDDH) values with the genomes of type strains of known Enterobacteriaceae species. The highest ANI and isDDH matches were with Lelliottia nimipressuralis and Enterobacter asburiae, respectively. The ANI and isDDH values support that the strain belongs to a novel species of the family Enterobacteriaceae. Phylogenomic analysis based on core genes revealed that strain 155047T was located in the Enterobacter-Leclercia-Lelliottia-Pseudenterobacter lineage. The highest ANI and average amino acid identity values between 155047T and any species of the Enterobacter-Leclercia-Lelliottia-Pseudenterobacter lineage were 84.43 % and 90.21 %, respectively, lower than the maximum inter-genus pairwise values. This indicates that 155047T belongs to a novel species of a novel genus in the lineage. Strain 155047T could be differentiated from Enterobacter, Lelliottia, Leclercia and Pseudenterobacter species by a negative reaction for ß-galactosidase and the ability to produce acid from l-fucose but not from sucrose. The names Huaxiibacter gen. nov. and Huaxiibacter chinensis sp. nov. are proposed for the novel genus and species, respectively. The type strain is 155047T (= GDMCC 1.2980T=JCM 35262T).

Rational design of highly efficient MXene-based catalysts for the water-gas-shift reaction.

Water molecules linked by hydrogen bonds are responsible for the high efficiency of bi-functional catalysts for the water-gas-shift (WGS) reaction because water can act as a proton transfer medium. Herein, we propose an associative pathway for the WGS reaction assisted by water to realize hydrogen production. Based on this pathway, we show by first-principles calculations that a large family of oxygen-terminated two-dimensional transition metal carbides and nitrides (MXenes) deposited on Au clusters are promising catalysts for the WGS reaction. Remarkably, the rate-determining barriers for *CO → *COOH on Au/Mn+1XnO2 are in the range from 0.15 eV to 0.39 eV, indicating that WGS can occur at much lower temperatures. Furthermore, a comprehensive microkinetic model is constructed to describe the turnover frequencies (TOF) for the product under the steady-state conditions. More importantly, there is a perfect linear scaling relationship between the rate-determining barriers of the WGS and the free energy of the adsorbed hydrogen. Besides, the potential energy diagrams for CO reforming reveal that the F terminations introduced in experiments have only a slight influence on the catalytic performance of the oxygen-terminated MXenes. Our work not only opens a new avenue towards the WGS reaction but also provides many ideal catalysts for hydrogen production.

Depressive symptoms, social support, and health-related quality of life: A community-based study in Shanghai, China.

BACKGROUND: Depressive symptoms erode both physical and mental aspects of health-related quality of life (HRQoL). Social support (SS) may improve HRQoL through its direct effects or buffering effects. The association among depressive symptoms, SS, and HRQoL has been studied in specific groups, but research in the general adult population remains limited. This study examined the association among depressive symptoms, SS, and HRQoL, including exploring whether SS (including its three dimensions: subjective SS, objective SS and support utilization) mediated or moderated the relationship between depressive symptoms and HRQoL among community-based adults. METHODS: We conducted a cross-sectional survey in six communities in Shanghai, China, and 1642 adult participants with complete information on depressive symptoms and/or SS, and HRQoL were included. Linear regression analysis was used to investigate the association among depressive symptoms, SS, and HRQoL. In addition, we explored the mediating and moderating role of SS in the relationship between depressive symptoms and HRQoL. RESULTS: More depressive symptoms were associated with lower physical HRQoL (B = -0.64, p < .001) and lower mental HRQoL (B = -0.83, p < .001). SS (B = 0.07, p = .02), specifically subjective SS (B = 0.09, p = .03), was positively related to mental HRQoL. After adjusting for covariates, we found no evidence for a mediating role of SS in the relationship between depressive symptoms and HRQoL, while SS (subjective SS and objective SS) moderated the association between depressive symptoms and mental HRQoL. LIMITATIONS: Due to the low voluntary participation rate of employees, participants represented approximately 50% of the individuals approached, thus limiting the generalizability of our findings. Data collected through self-report scales could lead to information bias. CONCLUSIONS: SS does not appear to underlie the relationship between depressive symptoms and HRQoL. However, interventions to increase SS (in particular, subjective SS and objective SS) should be studied to determine whether they may be beneficial in alleviating the adverse impact of depressive symptoms on mental HRQoL.

Glucosuric, renal and haemodynamic effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2, in patients with chronic kidney disease: A randomized trial.

AIM: To investigate the glucosuric, renal and haemodynamic effects of licogliflozin, a dual sodium-glucose co-transporter-1 and sodium-glucose co-transporter-2 inhibitor, in patients with chronic kidney disease (CKD). METHODS: This multiple-dose, parallel-group, phase II mechanistic study randomized 53 participants (aged 18-78 years, body mass index ≤ 50 kg/m2 ) with varying degrees of CKD or normal renal function to treatment with licogliflozin (50 mg once daily) or placebo for 7 days. The effects of licogliflozin on 24-h urinary glucose excretion (UGE24 ), renal function, haemodynamics, pharmacokinetics and safety were assessed. RESULTS: Licogliflozin treatment for 7 days significantly (p < .01) increased UGE24 from baseline in participants with normal renal function (adjusted mean change: 41.8 [33.6, 49.9] g) or with mild (32.6 [24.1, 41.0] g), moderate A (35.7 [28.6, 42.9] g) or moderate B (20.3 [13.1, 27.5] g) CKD, but not in severe (6.2 [-0.71, 13.18] g) CKD. Licogliflozin reduced urinary electrolytes (sodium, potassium and chloride), blood pressure and urinary volume to varying extents among different groups. Significant increases in renin (p < .05), angiotensin II (p < .05) and aldosterone (p < .01) levels were observed. Adverse events were generally mild, and most commonly included diarrhoea (94%), flatulence (68%) and abdominal pain (21%). CONCLUSION: Licogliflozin treatment results in significantly increased UGE and favourable changes in urinary electrolytes and haemodynamics in patients with varying degrees of CKD (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 ).

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

Development of Chinese mental health first aid guidelines for assisting a person affected by a traumatic event: a Delphi expert consensus study.

BACKGROUND: People who experience traumatic events have an increased risk of developing a range of mental disorders. Appropriate early support from people in a person's social network may help to prevent the onset of a mental disorder or minimize its severity. Mental health first aid guidelines for assisting people who have experienced traumatic events have been developed for high-income English-speaking countries. However, they may not be appropriate for use in China due to cultural and health care system differences. The aim of this study was to develop culturally appropriate guidelines for people providing mental health first aid to people affected by traumatic events in China. METHODS: A Delphi expert consensus study was conducted with two panels of experts in mainland China. Experts recruited to the panels included 32 professionals with expertise in the treatment of people affected by traumatic events and 31 people with lived experience of trauma or their carers. Panel members were sent a Chinese translation of the questionnaire used for developing English-language mental health first aid guidelines. This contained 168 items describing how to help people experiencing a potentially traumatic event. Panelists were asked to rate the importance of each statement for inclusion in the Chinese guidelines. They were also encouraged to suggest any additional statements that were not included in the original questionnaire. Statements were accepted for inclusion in the adapted guidelines if they were endorsed by at least 80% of each panel as very important or important. RESULTS: Consensus was achieved after three survey rounds on 134 statements for inclusion in the adapted guidelines for China, with 127 adopted from the guidelines for English-speaking countries and 7 new items from the comments of panelists. CONCLUSIONS: While many of the statements are similar to the guidelines for English-speaking countries, the panelists adapted the guidelines to China's context, including more detailed actions on how to discuss trauma and to help the person. These guidelines will be used to form the basis of a Mental Health First Aid (MHFA) training course for China, aimed at educating the public in providing support and advice to a person who is experiencing a potentially traumatic event. Further research is needed to investigate the use of the guidelines by the Chinese public and the implementation of MHFA training in appropriate settings in China.

Development of Chinese mental health first aid guidelines for problem drinking: a Delphi expert consensus study.

BACKGROUND: Alcohol use disorders have become the second leading cause of death for mental and substance use disorders in China. However, with early diagnosis and timely treatment, the burden can be mitigated. Family and friends of a person with alcohol use problems are well placed to recognize the signs, encourage professional help-seeking and help the person until treatment is received. We aimed to use the Delphi consensus methodology to develop guidelines about how members of the public can provide this "mental health first aid" to someone with problem drinking in China. METHODS: A Chinese-language questionnaire was developed, comprising statements that were endorsed for inclusion in the English-language problem drinking first aid guidelines for high-income countries. Participants were also encouraged to suggest new statements. These statements were evaluated by two Chinese expert panels - a professional panel and a lived experience panel - on how important they believed each statement was for members of the public providing mental health first aid to a person with problem drinking in China. Three survey rounds were conducted. To be included in the final guidelines, statements had to receive a "very important" or "important" rating from at least 80% of participants from each of the panels. RESULTS: The majority of statements were rated in the first survey round by 30 mental health professionals and 25 lived experience panel members. One hundred and eighty-one statements met the inclusion criteria and were used to form the guidelines. Compared to the English-language guidelines, the importance of family involvement and mutual support were highlighted by both Chinese expert panels, while a number of statements relating to low-risk drinking were rejected by the lived experience panel. CONCLUSIONS: The Chinese-language problem drinking first aid guidelines cover a variety of first aid strategies that members of the public can use when providing initial help to a person with problem drinking, such as how to communicate with the person and what to do if the person is intoxicated. These guidelines will be used as a stand-alone document will also inform the content of Mental Health First Aid training in China.

Barriers and facilitators to implementing measurement-based care for depression in Shanghai, China: a situational analysis.

BACKGROUND: Measurement-based care (MBC) is an evidence-based practice for depression, but its use by clinicians remains low. Enhanced MBC (eMBC), which uses digital technologies, can help to facilitate the use of MBC by clinicians and patients. Understanding factors that act as barriers and drivers to the implementation of MBC and eMBC is important to support the design of implementation strategies, promoting uptake by clinicians and patients. OBJECTIVE: This situational analysis identifies barriers and facilitators to the implementation of standard and eMBC at mental health centers in Shanghai, China. METHODS: We used mixed methods to develop a comprehensive understanding of the factors influencing MBC and eMBC implementation in Shanghai. This study took place across three mental health centers in Shanghai. We used situational analysis tools to collect contextual information about the three centers, conducted surveys with n = 116 clinicians and n = 301 patients, conducted semi-structured interviews with n = 30 clinicians and six focus groups with a total of n = 19 patients. Surveys were analysed using descriptive statistics, and semi-structured interviews and focus groups were analysed using framework analysis. RESULTS: Several potential barriers and facilitators to MBC and eMBC implementation were identified. Infrastructure, cost, attitudes and beliefs, and perceptions about feasibility and efficacy emerged as both challenges and drivers to MBC and eMBC implementation in Shanghai. CONCLUSIONS: The results of this study will directly inform the design of an implementation strategy for MBC and eMBC in Shanghai, that will be tested via a randomized controlled trial. This study contributes to the emerging body of literature on MBC implementation and, to the best of our knowledge, is the first such study to take place in Asia. This study identifies several factors that are relevant to the equitable delivery of MBC, recognizing the need to explicitly address equity concerns in global mental health implementation research.

Simultaneous determination of erythrocyte methotrexate polyglutamates by a novel and simple HPLC-MS/MS method with stable isotope-labeled internal standards.

Low-dose methotrexate is the first-line therapy for juvenile idiopathic arthritis. In vivo, methotrexate is converted into a series of methotrexate polyglutamates whose intracellular levels contribute significantly to its efficacy and toxicity. In this study, a novel high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to simultaneously determine erythrocyte methotrexate polyglutamates using stable isotope-labeled internal standards. Erythrocyte samples were precipitated by perchloric acid and then determined on an XBridge BEH C18 column with an XP vanguard precolumn in 12 min. The mobile phase consisted of 10 nM ammonium acetate (pH 10) and methanol under gradient elution. The detection was carried out in multiple reaction monitoring mode via an electrospray ionization source in positive ionization mode. The calibration curve for each metabolite was linear from 2.0 to 500.0 nmol/L (r2  > 0.99). The intraday and interday accuracies were between 93.0 and 107.0%, and the corresponding precisions were between 0.8 and 5.2%. The relative recovery ranged from 82.7 to 105.1%, and the relative matrix effect varied from 96.5 to 104.4%. The erythrocyte metabolites were stable for 30 days at -80°C. This simple and accurate method is applicable to routine monitoring of the concentration of erythrocyte methotrexate polyglutamates in patients to achieve individualized treatment.

Pharmacokinetics, metabolism, and excretion of licogliflozin, a dual inhibitor of SGLT1/2, in rats, dogs, and humans.

Absorption, metabolism, and excretion (AME) of licogliflozin, a sodium-glucose co-transporters (SGLTs) 1 and 2 inhibitor, were studied in male rats, dogs, and healthy male volunteers and reported.Oral absorption of licogliflozin was rapid (tmax < 1 h) with absorption estimated at 87%, 100% and 77% in rats, dogs and humans, respectively.Excretion of licogliflozin-related radioactivity was rapid and nearly complete following oral administration with total radioactivity recovery ranging from 73% in dogs, 92.5% in humans, to 100% in rats. Dose-related radioactivity was excreted in both urine and faeces with urinary excretion playing a slightly more important role in humans (∼56%) than in animal species (∼19-41%).Elimination of licogliflozin was predominantly via metabolism with the majority of the radioactivity dose (∼54-74%) excreted as metabolites across species.The principal biotransformation pathways involved direct glucuronidation and oxidation across all species. In humans, direct glucuronidation to M17 and M27 was the major pathway observed, accounting for ∼38% of the dose in excreta while oxidative metabolism also contributed to >29% of the dose in excreta. Oxidative pathways were predominant in animal species.

How can learning effects be measured in Balint groups? Validation of a Balint group questionnaire in China.

BACKGROUND: Balint groups aim to reflect doctor-patient relationships on the basis of personal cases. This study reports the validation of a questionnaire aimed at the identification of learning processes among Balint group participants in China. METHODS: This multicenter cross-sectional study was conducted during Balint group sessions in Beijing, Guangzhou and Shanghai. A heterogeneous sample of different professional groups was intended to adequately capture the reality of Balint work in China. After a Balint group session, the participants were asked to complete the Mandarin version of the Balint group session questionnaire (BGQ-C) and the group questionnaire (GQ), an internationally validated instrument to assess central dimensions of therapeutic relationships during group processes. RESULTS: Questionnaires from n = 806 participants from 55 Chinese Balint groups, predominantly comprising individuals with a medical background, were analyzed. Most participants were female (74.6%), and the average age was 34.2 years old (SD = 9.4). The results indicated good to very good reliability (Cronbach's α = .70 to .86; retest rs = .430 to .697). The verification of the construct validity of the BGQ-C showed satisfying convergent (rs = .465 to .574) and discriminant validity (rs = -.117 to -.209). The model was tested with a confirmatory factor analysis of a three-factor model (standardized root mean square residual = .025; comparative fit index = .977; Tucker-Lewis index = .971). The 3 empirically identified scales resulted in good model fit with the theoretical dimensions of Balint work postulated in the literature: "reflection of transference dynamics in the doctor-patient relationship", "emotional and cognitive learning" and "case mirroring in the dynamic of the group". Due to the high correlations between the factors, a single-factor model was possible. A group comparison between the German and Chinese samples showed different loadings across cultures. CONCLUSIONS: The BGQ-C is a quick-to-complete, item-based measuring instrument that allows the relevant dimensions of Balint group work to be recorded. This study suggests good psychometric properties of the Chinese version. Nevertheless, it must be assumed that the composition of constructs in the two countries is different.

First-in-human clinical trial to assess pharmacokinetics, pharmacodynamics, safety, and tolerability of iscalimab, an anti-CD40 monoclonal antibody.

Iscalimab is a fully human, CD40 pathway blocking, nondepleting monoclonal antibody being developed as an immunosuppressive agent. We describe a first-in-human, randomized, double-blind, placebo-controlled study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of iscalimab in healthy subjects and rheumatoid arthritis patients. Healthy subjects (n = 56) received single doses of intravenous iscalimab (0.03, 0.1, 0.3, 1, or 3 mg/kg), or subcutaneous iscalimab (3 mg/kg), or placebo. Rheumatoid arthritis patients (n = 20) received single doses of intravenous iscalimab (10 or 30 mg/kg) or placebo. Iscalimab exhibited target-mediated drug disposition resulting in dose-dependent and nonlinear pharmacokinetics. Complete (≥90%) CD40 receptor occupancy on whole blood B cells was observed at plasma concentrations >0.3-0.4 µg/mL. In subjects receiving 3 mg/kg iscalimab, antibody responses to keyhole limpet hemocyanin were transiently suppressed. CD40 occupancy by iscalimab prevented ex vivo human rCD154-induced expression of CD69 on B cells in whole blood. All doses were generally safe and well tolerated, with no clinically relevant changes in any safety parameters, including no evidence of thromboembolic events. Iscalimab appears to be a promising blocker of the CD40-CD154 costimulatory pathway with potential use in transplantation and other autoimmune diseases.