Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial.

Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC). Objective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone. Design, Setting, and Participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers. Interventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Main Outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety. Results: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group. Conclusions and Relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03581786.

If They Won't Know, I Won't Wait: Anticipated Social Consequences Drive Children's Performance on Self-Control Tasks.

This research evaluated the hypothesis that the act of offering an incentive produces anticipated social benefits that are distinct from the benefits associated with the incentive itself. Across three preregistered studies, 3- to 5-year-old children in China (total N = 210) were given an opportunity to wait for an additional sticker (Studies 1 and 3) or an edible treat (Study 2). Rewards were dispensed via a timer-controlled box that allowed the experimenter's apparent ability to learn how long children waited to be manipulated experimentally. Children waited only about half as long when they believed the experimenter would not find out how long they waited. When children were offered three prizes for waiting, anticipated social benefits still drove behavior at least as much as the reward. The findings demonstrate that children as young as 3 years are sensitive to anticipated social rewards when responding to offers of incentives.

Guilt promotes honesty in preschoolers.

The current study examined the influence of guilt on young children's honesty about their transgression. Children (N = 192; 4-6 years of age; 49.5% male, 50.5% female; middle-income Chinese families) participated in a modified temptation resistance paradigm where they were asked not to peek at a toy in the absence of an experimenter. Next, the children were randomly assigned to 1 of 3 conditions: (a) guilt condition, where children were induced with guilt using a revised mishap paradigm; (b) sadness condition, where children were induced with sadness by watching a video; and (c) baseline condition, where children did not participate in any additional emotion-inducing task. When later questioned about whether they peeked at the toy, children in the guilt condition were significantly less likely to lie compared with those in the sadness or baseline conditions. There was no significant difference between the sadness and baseline conditions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Apologies Repair Trust via Perceived Trustworthiness and Negative Emotions.

The present study examined whether perceptions of a transgressor's trustworthiness mediates the relationship between apologies and repaired trust, and the moderating role of negative emotions within this process. Chinese undergraduate students (N = 221) completed a trust game where they invested tokens in their counterpart, and either experienced no trust violation (i.e., half of the tokens returned), a trust violation (i.e., no tokens returned), or a trust violation followed by an apology. Participant's trust behavior was measured by the number of tokens they re-invested in their counterpart in a second round of the game. Participants also completed measures to assess perceptions of the transgressor's trustworthiness and emotional state. Results revealed that participants who received an apology were more likely to trust in their counterpart, compared to those who did not receive an apology, and this relationship was mediated by perceptions of the transgressor's trustworthiness. Further, the relationship between apologies and perceptions of the transgressors trustworthiness was moderated by negative emotions; apologies only improved perceptions of trustworthiness for participants who experienced less negative emotions.

Apologies repair children's trust: The mediating role of emotions.

The current study examined whether emotions mediate the relationship between apologies and repaired trust following a transgression. Children (9- and 11-year-olds; N = 180) completed a two-round trust game where if they invested tokens in their counterpart, the tokens tripled in value and the counterpart would decide how many tokens to return. Based on participants' condition, either half of the tokens were returned, none of the tokens were returned, or none were returned followed by an apology. Children's investment in their counterpart in the second round of the trust game was a measure of trusting behavior. In addition, children completed an emotion evaluation measure of their feelings toward their counterpart. Results demonstrate that children who received an apology following a transgression were significantly more likely to demonstrate trusting behaviors and positive emotions compared with children who received no apology. In addition, both positive and negative emotions were found to mediate the effect of an apology on trust.

Cerebrospinal fluid FGF23 levels correlate with a measure of impulsivity.

Fibroblast growth factor 23 (FGF23) is a bone-derived protein produced mainly by osteocytes and osteoblasts and at low levels in specific parts of the brain. It has been shown to associate with mood regulation. Lithium treatment gives rise to significant elevations of serum FGF23 levels in depressive patients. High peripheral blood FGF23 levels correlated with poor cognitive performance in hemodialysis patients. However, no direct evidence demonstrates a relationship between FGF23 and mood regulation. In this study, we aimed to measure the concentration of cerebrospinal fluid (CSF) FGF23 and to explore its relationship with a cluster of emotional characteristics. We measured CSF FGF23 levels in 96 male Chinese subjects. All subjects completed the Chinese version of the Barratt Impulsiveness Scale (BIS 11), the Beck Depression Inventory (BDI) and the Self-Rating Anxiety Scale (SAS). CSF FGF23 levels ranged from 12.8 to 99.3 pg/mL. Negative correlations were found between CSF FGF23 concentrations and BIS non-planning, BIS cognition and BIS total score (all p < 0.05). Nevertheless, except for the BIS cognition scores, these correlations became insignificant after Bonferroni correction. No correlations were found between CSF FGF23 concentrations and BDI or SAS scores. These findings suggest that CSF FGF23 levels correlate with a measure of impulsivity.

Strains of Group B streptococci from septic patients induce platelet activation via Toll-like Receptor 2.

Group B Streptococcus (GBS) causes life-threatening bacterial sepsis, especially in newborns and pregnant women. Patients suffering from sepsis often display low platelet counts, characterized by thrombocytopenia, because of platelet activation. In the present study, the roles of six GBS strains from septic patients in platelet aggregation, as well as the underlying mechanisms, were investigated. Incubation of platelets with three of the strains induced platelet aggregation, increased the secretion of cellular adhesin molecule CD62P and activation of GPIIb/IIIa. Furthermore, the GBS strains that induced platelet activation also caused an increase in the expression of Toll-like receptor (TLR) 2 in platelets. Pre-incubation of platelets with anti-TLR2 monoclonal antibody, but not anti-TLR4 monoclonal antibody, inhibited these functional responses induced by GBS. TLR2 stimulation also activated the phosphoinositide 3-kinase (PI3-K)/Akt signalling pathway in platelets, and inhibition of PI3-K significantly reduced GBS-induced platelet responses. Our results indicate that three of the GBS strains from the septic patients can trigger platelet activation by interacting with platelets, which involves the elevation of platelet TLR2 expression.

Intimate partner violence against married rural-to-urban migrant workers in eastern China: prevalence, patterns, and associated factors.

BACKGROUND: Intimate partner violence (IPV) is a significant public health issue among married rural-to-urban migrant workers, the largest group of internal migrants in China. This study aims to explore the prevalence, patterns and associated factors of intimate partner violence against married rural-to-urban migrant workers in eastern China. METHODS: A cross-sectional study was conducted in Zhejiang province in China between July 2015 and April 2016, and a total of 1,744 married rural-to-urban migrant workers ultimately took part in the study. Conflict Tactics Scales and several short demographic questions were applied. Data were principally analyzed with logistic regression. RESULTS: The majority of married rural-to-urban migrant workers were middle-aged couples with a low education level and a relatively long-term duration of migration in fixed migrant cities. Nearly 45% of married rural-to-urban migrant workers were experienced at least one incident of intimate partner violence during the past 12 months. The joint occurrence of multiple forms of violence is the most commonly reported features of intimate partner violence, especially three overlapping patterns of intimate partner violence. Some individual (education and age), relationship (marital satisfaction, premarital sex and extramarital affairs) and social (duration of migration and number of migratory cities) factors of the respondents, were negatively or positively associated with intimate partner violence against married rural-to-urban migrant workers. CONCLUSION: The results indicated that one out of two married rural-to-urban migrant workers experienced at least one incident of intimate partner violence during the past 12 months in China. Accordingly, there is an obvious demand of intervention and treatment activities to prevent and reduce the occurrence of intimate partner violence among the millions of migrant workers in China.

Children's Facial Trustworthiness Judgments: Agreement and Relationship with Facial Attractiveness.

This study examined developmental changes in children's abilities to make trustworthiness judgments based on faces and the relationship between a child's perception of trustworthiness and facial attractiveness. One hundred and one 8-, 10-, and 12-year-olds, along with 37 undergraduates, were asked to judge the trustworthiness of 200 faces. Next, they issued facial attractiveness judgments. The results indicated that children made consistent trustworthiness and attractiveness judgments based on facial appearance, but with-adult and within-age agreement levels of facial judgments increased with age. Additionally, the agreement levels of judgments made by girls were higher than those by boys. Furthermore, the relationship between trustworthiness and attractiveness judgments increased with age, and the relationship between two judgments made by girls was closer than those by boys. These findings suggest that face-based trait judgment ability develops throughout childhood and that, like adults, children may use facial attractiveness as a heuristic cue that signals a stranger's trustworthiness.

Prognosis of posterior osteophyte after anterior cervical decompression and fusion in patients with cervical spondylotic myelopathy using three-dimensional computed tomography study.

BACKGROUND: Inadequacy of posterior osteophyte resection in anterior cervical decompression and fusion (ACDF) surgery has long been a clinical concern as it may influence surgical outcome. There has been no agreement on the prognosis in the presence of remnant posterior osteophytes. METHODS: This study retrospectively investigated 26 cervical spondylotic myelopathy patients after ACDF in whom a remnant posterior osteophyte was identified by long-term follow-up CT scans (minimum of 2 years). Remnant posterior osteophytes and osseous spinal canal were measured and compared between pre-operation CT and long-term post-operation CT. The post-operative clinical outcomes were also studied. RESULTS: The remnant osteophytes did not obviously decrease in size in any patient and significantly enlarged in 10 patients, with a new posterior osteophyte developing in one patient. In patients whose remnant osteophyte is enlarged, the incidence of pseudoarthrosis, as well as clinical deterioration during follow-up was significantly higher than patients with stable osteophytes. CONCLUSION: Contrary to previous reports, none of the remnant posterior osteophytes decreased obviously in size during follow up. Despite the persistence of posterior osteophytes, ACDF is still effective in CSM treatment. Posterior osteophyte enlargement at fused segment appears to be associated with symptomatic pseudoarthrosis and clinical deterioration after surgery.

CHILDREN'S AND ADULTS' JUDGMENTS OF FACIAL TRUSTWORTHINESS: THE RELATIONSHIP TO FACIAL ATTRACTIVENESS.

Existing research suggests that adults make effective trustworthiness judgments based on facial attractiveness during initial interactions. However, little is known about how children judge trustworthiness from faces. The present study examined the facial features that contributed to judgments of trustworthiness and attractiveness by three groups of Chinese children aged 8 years old (n=34; 17 boys), 10 years old (n=34; 17 boys), and 12 years old (n = 34; 17 boys) and a comparison group of 37 undergraduates (M age=20.2 yr.; 16 men). Using FaceGen Modeler 3.1, a total of 400 East Asian adult faces (200 male, 200 female) portraying neutral emotions with direct gazes were generated. The faces were represented by 61 shape features and were presented for a maximum of 3,000 msec. in the center of the computer screen in randomized order. The participants were asked to judge whether each person was trustworthy and to rate the level of trustworthiness; 1 month later, the attractiveness of the same faces was judged using a similar procedure. The children and the adults used similar facial features to judge trustworthiness (e.g., the brow ridge, nose, and chin). Some of the facial features used by the different age groups as the basis for the trustworthiness and attractiveness judgments were similar. Facial attractiveness accounted for roughly 30 to 60% of the variance in the groups' trustworthiness judgments. Thus, facial attractiveness may serve as a heuristic property that signals trustworthiness and guides adaptive social decisions. More importantly, even children as young as 8 years old use a strategy similar to that of adults to make trustworthiness judgments, although some differences in the use of specific facial features were observed among the age groups.

Recovery of neurological functions in non-human primate model of Parkinson's disease by transplantation of encapsulated neonatal porcine choroid plexus cells.

Parkinson's disease (PD) is a neurodegenerative disease that is primarily characterized by degeneration of dopaminergic (DA) neurons in the substantia nigra (SN) and a loss of their fibre projections in the striatum. We utilized the neonatal porcine choroid plexus (CP), an organ that secretes cerebrospinal fluid containing various types of neurotrophic and neuroprotective factors, to ameliorate the Parkinsonian symptoms in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated rhesus monkeys without requiring immunosuppression. We demonstrate that transplanted encapsulated CP clusters (eCPs) significantly improved neurological functions in MPTP-treated monkeys during the course of six months after transplantation (p < 0.001) when compared with monkeys implanted with empty capsules or subjected to sham surgery. The improvement in neurological scores was accompanied by a corresponding improvement in apomorphine-induced circling behaviour (p < 0.001) as well as increased tyrosine hydroxylase (TH) staining in the striatum. Our results suggest that eCPs are a promising cell therapeutic agent to treat Parkinson's disease.

[Analysis of CD4(+)CD25(+)CD127(low/-) Treg cells in mice].

The quantitative identification and enrichment of viable regulatory T cells (Treg) requires reliable surface markers that are selectively expressed on Treg. Foxp3 is the accepted marker of natural Treg, but it cannot be used to isolate cells for functional studies. CD127 is a new surface marker expressed in Treg cells. In this study, two populations of Treg, including CD4(+)CD25(+)CD127(low/-) and CD4(+)CD25(+)Foxp3(+)T cells, and profiles of the Foxp3 expression in CD4(+)CD25(+)CD127(low/-) cells were compared to evaluate which population is better. The peripheral blood cells were collected and spleen suspension of BALB/C mice were prepared, and using triple staining CD4, CD25, CD127 and CD4, CD25, Foxp3. The profiles of Treg, including CD4(+)CD25(+)CD127(low/-) and CD4(+)CD25(+)Foxp3(+) were detected by flow cytometry. The quadruple staining CD4, CD25, Foxp3 and CD127 were used to determine the CD127 expression in CD4(+)CD25(+)Foxp3(+) cells. The results showed that on T cell subset the median expression levels of CD4(+), CD4(+)CD25(+) were 39.02%, 5.35% in peripheral blood and 23.49%, 3.86% in spleen. On CD4(+) T cell subset, the median expression level of CD4(+)CD25(+)CD127(low/-) and CD4(+)CD25(+)Foxp3(+)T cells were 7.13%, 3.97% in peripheral blood and 12.8%, 8.23% in spleen. The ratio of CD4(+)CD25(+)CD127(low/-) T cells was higher than that of CD4(+)CD25(+)Foxp3(+) cells in both peripheral blood and spleen cells (P < 0.01). The CD4(+)CD25(+)CD127(low/-) cells highly expressed Foxp3, while the CD4(+)CD25(+)Foxp3(+)T cells lowly expressed CD127. It is concluded that compared with the CD4(+)CD25(+)Foxp3(+) populations, CD4(+)CD25(+)CD127(low/-) T cells better fit the definition of naturally occurring regulatory T cells in peripheral blood cells and spleen of BALB/C mice. CD127(low/-) is a characteristic marker on surface of CD4(+)CD25(+) Treg cells, and has been confirmed to be more specific marker for quantitatively sorting Treg cells.

[Bactericidal permeability increasing protein inhibits lipopolysaccharide-mediated platelet activation in vitro].

This study was purposed to investigate the inhibitory effect of bactericidal permeability-increasing protein (BPI) on lipopolysaccharide (LPS)-mediated activation of platelets. Venous blood samples were obtained from 10 healthy volunteers and were prepared into platelet-rich plasma (PRP, 1 × 10(8)/ml). Experiments were divided into four groups: normal platelet group (untreated group); LPS group, BPI group and BPI+LPS group. PRP were stimulated by LPS (10 µg/ml) in the presence and absence of BPI (100 µg/ml) or BPI alone. Then platelets were harvested and determined for Toll-like receptor-4 (TLR-4) with flow cytometry (FCM), the supernatant was used for detection of cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) with enzyme-linked immunosorbent assay (ELISA). The results showed that as compared with normal platelet group, TLR-4 expression on platelets was significantly increased under LPS stimulation (P < 0.001); the levels of TNF-α and IL-6 in the supernatant were also remarkably elevated (P < 0.001). However, either TLR-4 expression or the cytokine levels significantly decreased in the presence of BPI when platelets underwent LPS-challenge (P < 0.05), but still were higher than that in normal platelet group. Stimulating the platelets with BPI alone could not enhance the TLR-4 expression and cytokine levels. It is concluded that BPI has the ability to inhibit the LPS-induced platelet activation.

[Hysterosalpingography combined with hysteroscopy-laporoscopy in diagnosing female infertility].

OBJECTIVE: To evaluate hysterosalpingography (HSG) combined with hysteroscopy-laparoscopy in diagnosing female infertility. METHODS: One hundred thirty three female infertile patients by clinical diagnosis were given HSG and hysteroscopy-laparoscopy, and the results were retrospectively analyzed. RESULTS: The total diagnostic coincidence rate of the two methods in diagnosing uterus-cervix infertility was 80.2%, while the coincidence rate of the two methods in diagnosing tubal infertility was 89.7%. CONCLUSION: HSG combined with hysteroscopy-laparoscopy is an optimal method in diagnosing female infertility at present.