Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective:To evaluate the role of necroptosis in paclitaxel-induced cognitive dysfunction in mice.Methods:Thirty SPF healthy male C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=10 each) using a random number table method: vehicle control group (Veh group), paclitaxel group (PTX group), and paclitaxel+ a specific inhibitor of necroptosis Necrostatin-1 group (P+ N group). In PTX group and P+ N group, paclitaxel 10 mg/kg (diluted to 5 mg/ml in anhydrous ethanol and castor oil [1∶1], and further diluted to 1 mg/ml in 0.9% normal saline before use) was intraperitoneally injected daily for 7 consecutive days to induce cognitive dysfunction. P+ N group received an intraperitoneal injection of Necrostatin-1 6.5 mg/kg (diluted to 10 mg/ml in dimethyl sulfoxide, and further diluted to 1 mg/ml in 0.9% normal saline before use) at 2 h before paclitaxel administration every other day, 4 times in total. Veh group received the equal volume of solvent at the matched time points as previously described in P+ N group. After establishment of the model, spontaneous locomotor activity was assessed using the open field test, followed by the novel object recognition test and the Morris water maze to evaluate the cognitive function. The animals were sacrificed after the end of the Morris water maze test, and the hippocampal tissues were collected for determination of the expression of necroptosis-related proteins receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3, mixed lineage kinase domain-like protein (MLKL), and phospho-MLKL (p-MLKL) (by Western blot analysis) and contents of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) (double immunofluorescence staining) and for observation of the localization of programmed necrosis cells (using enzyme-linked immunosorbent assay). Results:There were no significant differences in the total distance traveled and mean movement speed in the open field test or swimming speed in the Morris water maze test among the three groups ( P>0.05). Compared to Veh group, the time spent in the central zone in the open field and time spent in the original platform quadrant were significantly shortened, the discrimination index was decreased, the escape latency was prolonged, the number of crossing the original platform was reduced, the expression of RIPK1, RIPK3, MLKL and p-MLKL was up-regulated, the contents of TNF-α and IL-1β were increased, and the number of RIPK1-positive neurons was increased in PTX group ( P<0.05). Compared to PTX group, the time spent in the central zone in the open field test and time spent in the original platform quadrant were significantly prolonged, the discrimination index was increased, the escape latency was shortened, the number of crossing the original platform was increased, the expression of RIPK1, RIPK3, MLKL and p-MLKL was down-regulated, the contents of TNF-α and IL-1β were decreased, and the number of RIPK1-positive neurons was decreased in P+ N group ( P<0.05). Conclusions:Necroptosis in hippocampal neurons can lead to neuroinflammation, thus contributeing to paclitaxel-induced cognitive dysfunction in mice.

Objective To evaluate the interventional effects of virtual reality(VR)on cancer patients in pain,anxiety,cognitive function,upper limb function and quality of life.Methods Randomised controlled trials(RCTs)using VR technology on cancer patients were retrieved from databases of CNKI,Wanfang Database,SinoMed,VIP,PubMed,Web of Science,Embase,PsycINFO and Cochrane Library,from the inception of the databases to March 2023.Two reviewers independently examined and screened the literatures,followed by evaluation of the quality and extraction of relevant themes.Meta-analysis was conducted by using RevMan 5.3 to analyse the acquired data.Results A total of 9 RCTs involving 727 patients were included.The meta-analysis demonstrated that VR technology alleviated pain intensity in cancer patients[SMD=-1.31,95%CI(-1.96 to-0.66),P<0.001],relieved anxiety[SMD=-0.96,95%CI(-1.62 to-0.31),P=0.004],improved cognitive function[SMD=3.37,95%CI(1.74 to 5.00),P<0.001],and improved quality of life of cancer patients[SMD=0.67,95%CI(0.38 to 0.96),P<0.001].However,it posed unclear effect on upper limb function[SMD=-0.57,95%CI(-1.40 to 0.26),P=0.18].Conclusion VR technology shows potentials in alleviation of pain,reduction of anxiety and improvement of cognitive function and the quality of life in cancer patients,but it remains uncertain effect on upper limb function.However,due to heterogeneity in some of the results,more high-quality studies are required to validate the interventional effects of VR technology on cancer patients.

Objective: To investigate the incidence trend of diabetes among children and adolescents in Ningbo City, Zhejiang Province from 2011 to 2021, so as to provide the basis for the prevention and control of diabetes among children and adolescents. Methods: Data on diabetes incidence among children and adolescents aged 0 to 18 years in Ningbo City were collected through the Diabetes Monitoring Platform of the Ningbo Chronic Disease Collaborative Management System from 2011 to 2021. Crude incidence rates were calculated and standardized using data from the Sixth National Population Census in 2010. The trend of incidence rates were analyzed by average annual percent change (AAPC). Results: A total of 701 cases of diabetes among children and adolescents were reported in Ningbo City from 2011 to 2021. The crude and standardized incidence rates were 6.86/105 and 7.27/105, respectively, showing upward trends (AAPC=5.886%, 7.147%, both P<0.05). The crude and standardized incidence rates of type 1 diabetes mellitus were 3.36/105 and 3.35/105, respectively, with no significant trend observed (AAPC=1.229%, 1.449%, both P>0.05). The crude incidence rate was higher in children and adolescents aged 10 to <15 years (4.56/105) than in other age groups (all P<0.05). The standardized incidence rate was higher in females than in males (3.49/105 vs. 3.04/105, P<0.05). The standardized incidence rate was higher in urban areas than in rural areas (3.60/105 vs. 3.15/105, P<0.05). The crude and standardized incidence rates of type 2 diabetes mellitus were 3.43/105 and 3.87/105, respectively, showing upward trends (AAPC=4.904%, 7.579%, both P<0.05). The crude incidence rate was higher in children and adolescents aged 15 to 18 years (10.53/105) than in other groups (all P<0.05). The crude incidence rates in children and adolescents who aged 10 to <15 years and 15 to 18 years showed upward trends (AAPC=15.030%, 6.637%, both P<0.05). The standardized incidence rate was higher in males than in females (4.01/105 vs. 3.57/105, P<0.05). The standardized incidence rate was higher in urban areas than in rural areas (4.57/105 vs. 3.34/105, P<0.05). Conclusions From 2011 to 2021, the incidence of type 2 diabetes mellitus showed an upward trend, with cases mainly concentrated in children and adolescents aged 15 to 18 years, males, and those living in urban areas. The incidence of type 1 diabetes mellitus remained stable, with cases mainly concentrated in children and adolescents aged 10 to <15 years, females, and those living in urban areas.

Objective:To observe the effects of rolling method massager on local tissue morphology, tissue and serum TNF-α and IL-1β in rabbits with skeletal muscle injury at different time points; To investigate the mechanism of temporal effect of rolling method action on skeletal muscle injury.Methods:Totally 72 New Zealand rabbits were divided into blank group, model group and rolling method treatment group according to random number table method, with 24 rabbits in each group. Rabbits in each group were divided into 1 d, 3 d, 5 d, 7 d, 9 d and 11 d subgroups according to the time point of injury, with 4 rabbits in each group. Blunt contusion was used to model the model group and the rolling method treatment group. Each subgroup of the rolling method treatment group was subjected to rolling method intervention for 3 d, using a homemade rolling method massager, 2 times/d, 3 min/time. At 24 h after the completion of the intervention, the histomorphological changes were observed by HE staining, and the TNF-α and IL-1β contents in serum and damaged skeletal muscle tissues were detected by ELISA.Results:Compared with the blank group, the inflammatory cell infiltration in the model group was obvious, edema was severe, and myofibers were broken; the inflammatory cell infiltration in the 1 d rolling method treatment group was intensified, myocytes were apoptotic, and myofibers were broken and necrosed more seriously; the inflammation in the 7 d rolling method treatment group was obviously improved with the best effect, and the difference with normal healthy muscle tissue was smaller. After modeling, TNF-α and IL-1β levels in skeletal muscle tissues and serum TNF-α levels were higher in the 3 d model group than in the 1 d model group ( P<0.05). Compared with the blank group, TNF-α and IL-1β levels in skeletal muscle tissues and serum increased in each subgroup of the model group and each subgroup of the rolling method treatment group ( P<0.01); Compared with the 1 d model group, TNF-α and IL-1β levels in skeletal muscle tissues and serum TNF-α levels increased in the 1 d rolling method treatment group. The levels of TNF-α and IL-1β in the 3 d, 5 d, 7 d, 9 d and 11 d rolling method treatment group were lower than those in the model group subgroup ( P<0.05). TNF-α and IL-1β levels in skeletal muscle tissues and serum TNF-α levels were higher in the 1 d, 3 d and 5 d rolling method treatment group than in the 7 d rolling method treatment group ( P<0.05). TNF-α levels in skeletal muscle tissues were higher in the 1 d and 3 d rolling method treatment group than in the 7 d rolling method treatment group ( P<0.05). Conclusion:The inflammatory factors in the rolling treated group were significantly higher at 1 d after skeletal muscle injury, indicating that treatment with the rolling method was inappropriate at this time; seven days after injury, the application of rolling method can reduce the inflammatory effect, accelerate the repair of skeletal muscle, and improve the quality of functional recovery.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.

Objective:To analyze post-discharge coping difficulty of delivery women based on social ecosystem theory.Methods:From March to May 2022, 23 delivery women from Affiliated Hospital of Guilin Medical University were selected as research objects by the purpose sampling method. The phenomenological research method was used to conduct face-to-face semi-structured interview. The content analysis method was used to analyze the data and extract the theme.Results:A total of 3 themes and 11 sub-themes were extracted. The micro level included 1 theme, namely care stress and self recovery problems coexist, including difficulty in breastfeeding, feeling powerless to raise children, anxiety, disturbance in body recovery of delivery women, prominent sense of sleep deprivation, insufficient knowledge of infant care and body recovery. The mesoscopic level included 1 theme, namely changes in life atmosphere, including caregiver relationship conflict, lack of family support and sense of connection. The macro level included 1 theme, namely interaction of social environment, including living environment not meeting expectations, sense of economic burden, expectation of instant professional guidance.Conclusions:The post-discharge coping difficulty of delivery women is complex and varied. Medical staff should use information technology, family synchronous empowerment, social worker intervention and other methods to meet the needs of delivery women, reduce their post-discharge coping difficulties.

Objective:To explore the clinical value of preconception expanded carrier screening (PECS) in Chinese Han population of childbearing age.Methods:The gene detection results of infertile couples with PECS in the Reproductive Medicine Center of the Second Affiliated Hospital of Zhengzhou University from September 2019 to May 2022 were analyzed retrospectively. The carrier rate of pathogenic gene, the detection rate of high-risk couples and the clinical outcome of high-risk couples were counted and analyzed.Results:A total of 1 565 patients received PECS and they were all Chinese Han. A total of 504 patients received the 108 extended monogenic diseases testing, including 420 females and 84 males, the overall carrier rate of the target genes was 30.75% (129/420), and the detection rate of high-risk couples was 1.19% (1/84), the higher carrier rates of the tested genes were MMACHC [2.58% (13/504)], ATP7B [2.38% (12/504)], SLC22A5 [2.18% (11/504)], GALC [1.79% (9/504)], PAH [1.79% (9/504)] and MLC1 [1.19% (6/504)], the rest are less than 1%. There were 555 patients accepted FMR1 gene detection, and 5 patients with FMR1 gene mutation, accounting for 0.90%. Testing for direct relatives of patients with complete mutations, her mother is a pre mutation carrier with a CGG repeat count of 105. A total of 502 patients accepted SMN1 gene testing. Totally 14 femals and 2 males were found to be SMN1 gene carriers in this study, with a carrier rate of 3.19%. Conclusion:The carryier rate of single gene recessive disorder is high in the population. Screening before pregnancy can provide birth health guidance for patients, help them to choose preimplantation genetic testing for monogenic/single gene disorders (PGT-M) and prenatal diagnosis, to avoid the birth of silk children.

Background: Studies have shown that transient receptor potential (TRP) channels play important roles in gastroesophageal reflux disease (GERD), however, the relationship between TRPV1 and TRPM8 in reflux esophagitis (RE) remains unclear. Aims: To investigate the expressions of TRPV1, TRPM8 and their correlation in guinea pigs with RE. Methods: Thirty male guinea pigs aged 3⁃4 weeks were randomly divided into 3 groups: blank control group, negative control group and model group, with 10 animals in each group. Guinea pigs in model group and negative control group were given esophageal perfusion with 0.1 mol/L HCl containing 0.5% pepsin and normal saline, respectively, once a day for 14 days; guinea pigs in blank control group were free to drink sterile water for 14 days. On day 15, the esophagus was dissected for macroscopic and histopathological examination, and Western blotting and/or real⁃time PCR were used to detect the expression levels of TRPV1, TRPM8, GNAQ (an isoform of G protein), and the tight junction proteins and proinflammatory cytokines in esophageal tissue. The co⁃localization of TRPV1 and TRPM8 was assessed by immunofluorescence. Results: Esophageal mucosal congestion, hyperplasia of esophageal epithelial cells, infiltration of inflammatory cells, as well as up⁃regulation of proinflammatory cytokines and down⁃regulation of tight junction proteins were observed in esophageal tissue of guinea pigs in model group, which indicated the successful RE model construction. As compared with the negative control group, expression levels of TRPV1 and GNAQ mRNA and protein were significantly increased, while expression levels of TRPM8 mRNA and protein were significantly reduced in esophageal tissue of guinea pigs in model group (all P<0.05). TRPV1 and TRPM8 channels were co ⁃ localized in the lamina propria of esophageal mucosa. Conclusions: There is a certain equilibrium mechanism between TRPV1 and TRPM8 channels in RE models. G protein⁃coupled receptor signaling pathway and the downstream TRPV1/TRPM8 might be involved in the occurrence and development of GERD.