Background and aims Cancer cachexia is prevalent in various cancers and is associated with chemotherapy toxicity. However, limited data exist on the relationship between cachexia and immune-related adverse events (irAEs). The aim of this study is to explore the correlation between cancer cachexia and irAEs and its possible mechanism. Methods A murine model of orthotopic hepatocellular carcinoma (HCC) with cachexia was developed to evaluate the impact of T-cell infiltration into multiple tumor-free organs on the occurrence of irAEs. Single-cell RNA sequencing of thymic stromal cells was performed. Additionally, patients with advanced cancers receiving anti-programmed cell death protein 1/ligand 1 (PD-1/L1) antibody treatment were followed to investigate the relationship between cachexia and irAEs. Results Inflammatory cell infiltration was observed in multiple tumor-free organs of cachexic HCC mice but not in non-cachexic controls. Immunofluorescence confirmed that the infiltrating cells included CD4+ and CD8+ T cells. Morphological assessment and hematoxylin–eosin staining revealed thymic atrophy in cachexic HCC mice. Single-cell RNA sequencing of thymic stromal cells showed a reduction in medullary thymic epithelial cells (mTECs) II and III in cachexic mice. Autoimmune regulator (Aire) downregulation was accompanied by decreased expression of tissue-restricted antigens in mTECs. T cells from cachexic HCC mice induced organ-specific inflammation and T-cell infiltration in multiple organs of tumor-free mice. Following anti-mouse PD-1 antibody treatment, the incidence of inflammation in multiple organs markedly increased in cachexic HCC mice and in tumor-free mice that had received T cells from the cachexic HCC mice. Flow cytometry and immunofluorescence analyses revealed enrichment of thymic monocytic myeloid-derived suppressor cells (M-MDSCs) in cachexic HCC mice. M-MDSCs infiltrated the thymus in cachexic mice with cancer, and they induced apoptosis of mTECs from tumor-free mice in vitro via nitric oxide production. Transfer of M-MDSCs led to inflammatory cell infiltration in multiple organs and thymic involution in tumor-free mice without affecting body weight. Sixty-four patients with advanced cancer receiving anti-PD-1/L1 therapy were enrolled. Patients who developed irAEs had higher levels of circulating M-MDSCs than those who did not. Moreover, patients with cachexia (body mass index (BMI) < 20 kg/m2 or ≥5% weight loss over the past 6 months) had elevated M-MDSC levels. Patients with both high M-MDSC levels and low BMI or weight loss ≥5% experienced more irAEs (hazard ratio: 2.333; 95% confidence interval: 1.231–4.423). Conclusions M-MDSCs in cachexic mice induced mTEC apoptosis through nitric oxide production, impairing T-cell negative selection and promoting autoimmune T-cell infiltration into tumor-free organs. Cancer cachexia-related M-MDSCs may serve as predictive biomarkers for irAEs in patients with advanced cancer. Graphical abstract

This study aimed to investigate the incidence of patent processus vaginalis (PPV) in pediatric patients with a unilateral nonpalpable testis and explore the associated factors. From May 2014 to April 2017, 152 boys who were diagnosed with a unilateral nonpalpable testis and underwent laparoscopy in Shanghai Children's Hospital (Shanghai, China) were included in this study. The data were collected and reviewed, and the results were analyzed regarding the age at operation, side, development, and position of the nonpalpable testis. The mean age of the patients was 2.6 (standard deviation: 2.3) years. The testis was absent in 14 cases, nonviable in 81 cases, and viable in 57 cases. The incidence of PPV was 37.5% (57 of 152) on the ipsilateral side and 16.4% (25 of 152) on the contralateral side. The ipsilateral PPV was more prevalent when the nonpalpable testis occurred on the right side ( P < 0.01). Besides, patients with a viable testis had a greater incidence of ipsilateral PPV than those with a nonviable or absent testis ( P < 0.01). Moreover, this rate was the highest when the testis was in the abdominal cavity and the lowest when the testis was in the scrotum (both P < 0.01). However, the incidence of contralateral PPV was independent of all the factors. In conclusion, in children with a nonpalpable testis, the incidence of an ipsilateral PPV was significantly related to the side, development, and position of the testis, while it was independent of these factors on the contralateral side.
Male ; Child ; Humans ; Infant ; Child, Preschool ; Testis ; China ; Testicular Hydrocele/surgery* ; Laparoscopy ; Scrotum ; Hernia, Inguinal/surgery* ; Cryptorchidism/surgery*

OBJECTIVE: To explore the method of measuring root volume with cone-beam computed tomography (CBCT) three-dimensional reconstruction technology, and to study root length and root volume of upper and lower central incisors in patients with skeletal Class Ⅲ malocclusion treated by surgical orthodontic treatment. METHODS: Twenty patients with skeletal Class Ⅲ malocclusion undergoing surgical orthodontic treatment were selected. CBCT data at three time points, before decompensation treatment (T0), after decompensation treatment (before orthognathic surgery, T1), and the end of post-operative orthodontic treatment (T2) were collected. Three-dimensional reconstruction technology was used to measure the root length and root volume of the upper and lower central incisors (including total root volume, cervical root and apical root), calculate the percentage of reduction volume, and measure the distance of tooth movement after orthodontic treatment. Data were statistically analyzed by SPSS 20.0 software. Least significant difference (LSD) method was used for pair comparison between the groups subject to normal distribution, and non-parametric test was used for comparison between the groups not subject to normal distribution. The differences of root length and root volume of upper and lower incisors were compared, and the characteristics of root absorption were analyzed. RESULTS: Root length and root volume of the upper and lower central incisors were reduced during the surgical orthodontic treatment (P < 0.05) in cases. Both the root volume of cervical root and apical root were significantly reduced (P < 0.05), the reduction of apical root was more significant. The percentage of root volume reduction of the upper central incisor was (30.51±23.23)%, and lower central incisor (23.24±11.96)%. Compared with the upper central incisor, the root volume reduction amount and percentage of the lower central incisor were smaller, and apical root volume reduction of the upper central incisor was greater than that of the lower central incisor, which was statistically significant (P < 0.05). During pre-surgical orthodontic treatment, maxillary central incisor palatal moving was in a controlled tipping manner, and the mandibular central incisor tipped labially. CONCLUSION In patients with skeletal Class Ⅲ malocclusion, root length and total root volume of upper and lower central incisors decreased during surgical orthodontic treatment. Root volume measurement indicated that the cervical root also had root resorption. The difference in root resorption of the upper and lower central incisors might be related to the distance and direction of teeth movement. CBCT three-dimensional reconstruction will compensate for the limitation of root length measurement in evaluating root resorption.
Cone-Beam Computed Tomography/methods* ; Humans ; Incisor/diagnostic imaging* ; Malocclusion, Angle Class III/surgery* ; Maxilla/surgery* ; Root Resorption/etiology*

Objective To study the distribution of sleep duration in mid－pregnancy women and examine its association with prehypertension ( PHT) ． Methods In the baseline survey of a prospective cohort study，943 women in mid－pregnancy were recruited in Guangzhou，China in 2017－2018． A standardized questionnaire was used to assess demographic characteristics，sleep duration and other lifestyles． We obtained maternal blood pressure values，weights，heights，and medical histories from medical records． Multivariate logistic regression was conducted to examine the association between sleep duration and PHT． Ｒesults The average daily sleep duration of women in mid －pregnancy was ( 10. 41 ± 1. 67 ) hours，and it was negatively related to age and educational level． Overall，98. 33% of pregnant women had a daily sleep duration ≥ 7 h and the distribution was related to passive smoking． The average night time sleep duration was ( 9. 48±1. 21 ) hours，and it was negatively related to age and educational level． The daytime sleep duration was ( 0. 93 ± 0. 69 ) hours，and it was positively associated with physical activity． The average bedtime was( 22 ∶ 42 ± 1．24) ，and it was positively associated with passive smoking． The prevalence of PHT was 9. 61%． We did not observe any significant association between sleep duration and PHT． Conclusions The mid－pregnancy women in Guangzhou had relatively long sleep duration， and it differed by maternal age，educational level，physical activity，and passive smoking． There was no significant association between sleep duration and PHT．

Endodermal Sinus Tumor/surgery* ; Humans ; Infant ; Magnetic Resonance Imaging ; Male ; Orchiectomy/methods* ; Teratoma/surgery* ; Testicular Neoplasms/surgery* ; Testis/surgery* ; Treatment Outcome

AIM:To observe the expression of microRNA-126-5p during myocardial injury and its role in myo-cardial cell injury induced by adriamycin(also called doxorubicin, DOX).METHODS: The BALB/c mouse model of DOX-induced acute and chronic myocardial injury was established via intraperitoneal injection of DOX.HE staining was applied to observe the morphological changes of myocardial tissues.Lactate dehydrogenase(LDH)in serum was detected and PowerLab system was used to detect the influence of DOX on the changes of ±dp/dtmax.The expression of microRNA-126-5p in injured myocardial tissues and the H 9c2 cells exposed to DOX was detected by real-time PCR.Gain-and loss-of-function experiments were conducted to detect the role of microRNA-126-5p in H9c2 cells treated with DOX on LDH release and caspase-3 activation.RESULTS:In acute and chronic DOX myocardial damage models in mice,HE staining showed disarranged myocardial fibers, dissolved myofibril and inflammatory cell infiltration.Higher serum LDH level and lower ±dp/dtmaxin DOX-treated mice than those in normal mice were found.Compared with the normal mice, the expression level of microRNA-126-5p was significant increased in the myocardium with DOX-induced injury.Similarly,the expression level of microRNA-126-5p was significant increased in the H9c2 cells treated with DOX.In addition, over-expression of microRNA-126-5p decreased cell viability and promoted apoptosis,while microRNA-126-5p ablation promoted the viability and inhibited the apoptosis of H9c2 cells.CONCLUSION:The microRNA-126-5p expression is up-regulated in myocar-dial injury induced by DOX,and microRNA-126-5p inhibits cell viability and promotes apoptosis induced by DOX.

The supply deficiency of crude medicinal plant of Paris polyphylla var. chinensis has become a bottleneck for related medicinal industry. An important approach to increase herbal production is to breed high-yield cultivated variety, which characterized ideal plant morphology. In the present study, we collected 99 wild germplasm resources of P. polyphylla and then measured their 12 main agronomic traits and contents of polyphyllin Ⅶ,Ⅵ,Ⅱ,Ⅰ. Followed analyses were used to characterize those traits and explore the potential connection with herbal yield or quality. The results showed that: ①There was ample morphological diversity in wild P. polyphylla, whose variation of agronomic traits reduced according to followed order: content of polyphyllin, weight of dry rhizome, petiole length, stem length, petal length, pedicel length, sepal length, leaf width, leaf length, sepal width, leaf number, stamen number, petal number. ② Most of those traits were significantly correlated to each other and generally represented the characterization of photosynthetic organs or reproductive organ. ③The total content of polyphyllin Ⅶ,Ⅵ,Ⅱ,Ⅰvaried between 0.02% and 0.87% and averagedat 0.13%, which showed no significant correlation with any agronomic trait. ④Plant breeders should play more attention on those germplasm resources with large leaves, large sepals and high stem.

Objective:To investigate the role of bone morphogenetic protein 2/7 heterodimer (BMP-2/7)in the osteogenesis of human adipose-derived stem cells (hASCs).Methods:hASCs were exposed to three different treatments in vitro:osteogenic medium with 1 50 μg/L BMP-2/7 (experimental group), osteogenic medium alone (OM group)and proliferation medium (PM group).After 1 ,4 and 7 days of osteogenic induction,the amount of cellular DNA was measured to investigate the cytotoxicity.After 7 and 1 4 days,alkaline phosphatase (ALP)staining and quantification were performed to test the activity of ALP.After 21 and 28 days,the calcification deposition was determined by Alizarin Red S (ARS)stai-ning and quantification.The expressions of the osteoblast-related genes were tested on days 1 ,4,7 and 1 4.In the in vivo study,6 nude mice were used and 4 groups were set and implanted subcutaneously into the back of nude mice:(1 )β-TCP scaffold only (scaffold control group );(2 )β-TCP scaffold with hASCs cultured by PMin vitro for 1 week (PMcontrol group);(3)β-TCP scaffold with hASCs cultured by OM in vitro for 1 week (OM control group);(4)β-TCP scaffold with hASCs cultured by OM with 1 50 μg/L BMP-2/7 in vitro for 1 week (test group).After 4 weeks of implantation,histological staining was performed to evaluate the in vivo osteogenesis of hASCs.Results:After induction for 1 day,there was no significant difference between the experimental group and the PM group on the cellular DNA con-tent (P>0.05 ).After 4 days,the cellular DNA content increased under the stimulation of BMP-2/7 (P<0.05).On day 7,there was no significant difference among the three groups (P>0.05).ALP ac-tivity was higher by the induction of BMP-2/7 than in OMalone and PM(P<0.05).More mineraliza-tion deposition and more expressions of osteoblast-related genes such as Runx2,ALP,COL-1 A1 and OC were determined in the experimental group at different time points (P<0.05).HE staining showed that, in the test group and OM control group,the extracellular matrix (ECM)with eosinophilic staining were observed around hASCs,and newly-formed bone-like tissues could be found in ECM around the scaffold materials.Moreover,compared with the OM control group,more bone-like tissues could be observed in ECMwith typical structure of bone tissue in the test group.Masson’s trichrome staining showed that more expression of collagen could be observed in ECM in the test group compared with the other groups.There was small amount of expression of collagen in the OM and PM control groups.No obvious positive results were found in the scaffold group.Conclusion:BMP-2/7 heterodimer plays a significant role in the osteo-genesis of hASCs and is able to enhance the osteogenic differentiation of hASCs in vitro and in vivo.

The present study was designed to synthesize and evaluate a series of benzylisoquinoline derivatives. These compounds were synthesized by Bischler-Napieralski cyclization to yield 1-benzyl-3,4-dihydroisoquinolines, and the products were obtained by reductions. All these compounds were identified by MS, (1)H NMR and (13)C NMR. The inhibitory activities on pancreatic lipase and preadipocyte proliferation for the synthesized compounds and alkaloids from Nulembo nucifera were assessed in vitro. Most of the compounds showed inhibitory activities on both pancreatic lipase and preadipocyte proliferation. Particularly, compounds 7p-7u and 9d-9f exhibited significant inhibitory activity on pancreatic lipase while compounds 7c, 7d, 7f, 7g, 7i, and 7j potently inhibited the proliferation of 3T3-L1 preadipocytes. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for human diseases.
Adipocytes ; cytology ; drug effects ; Benzylisoquinolines ; chemical synthesis ; chemistry ; pharmacology ; Cell Proliferation ; drug effects ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Humans ; Lipase ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship

OBJECTIVETo evaluate the effects of the 25 Gy ⁶⁰Co irradiation on the physiological and biochemical properties and the functions of the platelets during storage.

METHODSA total of 15 bags of platelets were apheresis-collected from 15 healthy donors, and each bag of platelets were divided into 2 parts, then the platelets were divided into the control group (without 25 Gy ⁶⁰Co irradiation) and the irradiated group (with 25 Gy ⁶⁰Co irradiation) groups. The two groups of platelets were kept under the condition of (22 ± 2) °C and shaken. The Platelet count and pH value were detected on the d 1, d 2, d 3, d 4 and d 5. The variables such as R, K values, α angle and maximal amplitude (MA) were measured by thrombelastography on the same days. Hypotonic shock response (HSR), morphological score were devised.

RESULTSThere were no statistically significant difference in Plt counts, mean platelet volume (MPV), platelet distribute width (PDW) and pH between the two groups (P > 0.05), and Plt count decreased on the end of storage. There were no marked changes in HSR level and morphological score between the two groups during storage, and there were no significant difference between the two groups (P > 0.05). In the TEG analysis there were no significant difference of the R, K, α angle and MA values between the two groups (P > 0.05). R value showed upward trend increased along with prolongation of preserved time (P < 0.01), no significant changes in α angle (P > 0.05), K value was slightly higher and MA value was lower in the last day of storage than the days 1-4 (P < 0.01), respectively.

CONCLUSION25 Gy ⁶⁰Co gamma-ray irradiation can not damage the physiological, biochemical properties and the functions of the platelets during storage. In order to ensure the best curative effect, it is suggested that no matter the platelets were irradiated or not, the platelets should be used as soon as possible.