Immune checkpoint inhibitors(ICIs)mainly promote anti-tumor immunity by relieving tumor immune suppression.Interferon-γ(IFN-γ)plays an important role in increasing tumor antigen presentation,inducing immune cell infiltration,and directly inducing tumor cell apoptosis,becoming a key factor in improving the efficacy of immunotherapy.The abnormal signaling pathway of IFN-γ and its own effect on promoting tumor are the key mechanisms that trigger resistance to ICIs therapy.Immunotherapy,when combined with IFN-γ or IFN-γ inducers,can effectively restore the presentation ability of MHC-I,increase immune cell infiltration,and thus improve the efficacy of immunotherapy.In addition,domestic and foreign scholars have achieved certain therapeutic effects on clinical trials by normalizing the IFN-γ signaling pathway and combining ICIs with JAKi.This review mainly introduces the role of IFN-γ in the treatment of tumor ICIs,providing direction for potential treatment strategies to reverse ICIs resistance and further provi-ding theoretical basis for clinical application.

Objective:To investigate the correlation between hearing loss and microvascular complications in diabetes.Methods:This cross-sectional study conducted the data from 572 patients with diabetes hospitalized in the Endocrinology Department of the General Hospital of Southern Theater Command from September 2022 to July 2023. All participants underwent electrical audiometry and acoustic immittance in the ENY department. Based on the audiometric results, participants were categorized into normal hearing group and hearing loss group. Additionally, 572 non-diabetic patients from the outpatient department were enrolled as the non-diabetic group. The general information and laboratory results were collected and compared using t test, rank sum test or χ2 test. Binary logistic regression analysis was used to evaluate the association of diabetic hearing loss with diabetic kidney disease(DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results:Among 572 patients with diabetes, 429 suffered from hearing loss and 143 were normal. χ2 test showed significant differences in combined DKD and DPN between two groups, but not in DR. Multivariate binary logistic regression analysis identified DKD and DPN as risk factors for hearing loss, but no correlation was found with DR. Conclusion:Diabetic patients with DKD or DPN should be monitored for potential hearing loss. Early screening and treatment are crucial to prevent severe hearing impairment.

Diabetes mellitus (DM) is a major metabolic disease endangering global health, with diabetic nephropathy (DN) as a primary complication lacking curative therapy. Sporoderm-broken spores of Ganoderma lucidum (GLP), an herbal medicine, has been used for the treatment of metabolic disorders. In this study, DN was induced in Sprague-Dawley rats using streptozotocin (STZ) and a high-fat diet (HFD), and the protective mechanisms of GLP were investigated through transcriptomic, metabolomic, and network pharmacology (NP) analyses. Our results demonstrated that GLP intervention ameliorated renal damage and inflammation levels in DN rats. Integrative metabolomic and transcriptomic analysis revealed that GLP treatment modulated glucose and cellular energy metabolisms by regulating relevant genes. GLP significantly suppressed the inflammations by impacting glucose and energy metabolism-related gene expression (Igfbp1 and Angptl4) and enhanced metabolic biomarkers of 4-Aminocatechol. In addition, NP analysis further indicated that GLP may efficiently alleviate DN via immune-related pathways. In conclusion, this study provides supportive evidence of the anti-inflammatory effects of GLP supplements, highlighting their potential for promising clinical applications in treating DN.

Immune checkpoint inhibitors(ICIs)mainly promote anti-tumor immunity by relieving tumor immune suppression.Interferon-γ(IFN-γ)plays an important role in increasing tumor antigen presentation,inducing immune cell infiltration,and directly inducing tumor cell apoptosis,becoming a key factor in improving the efficacy of immunotherapy.The abnormal signaling pathway of IFN-γ and its own effect on promoting tumor are the key mechanisms that trigger resistance to ICIs therapy.Immunotherapy,when combined with IFN-γ or IFN-γ inducers,can effectively restore the presentation ability of MHC-I,increase immune cell infiltration,and thus improve the efficacy of immunotherapy.In addition,domestic and foreign scholars have achieved certain therapeutic effects on clinical trials by normalizing the IFN-γ signaling pathway and combining ICIs with JAKi.This review mainly introduces the role of IFN-γ in the treatment of tumor ICIs,providing direction for potential treatment strategies to reverse ICIs resistance and further provi-ding theoretical basis for clinical application.

ObjectiveTo explore sleep disturbance in preschool children with autism spectrum disorder (ASD) and analyze the relationship between sleep disturbance and social behavior. MethodsFrom December, 2020 to December, 2022, 221 preschool children with ASD from Beijing Bo'ai Hospital and other two institutes, and 246 healthy preschool children socially recruited were investigated with Children's Sleep Habits Questionnaire (CSHQ). A total of 47 ASD children and 47 healthy children were selected from them to wear a sleep monitoring watch for seven days, while the ASD children were evaluated with Gesell Development Diagnosis Scale (GDDS), Psychoeducational Profile-Third Edition (PEP-3), Autism Diagnostic Observation Schedule-2 (ADOS), Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS). ResultsAll the factor-scores were more in the ASD children than in the healthy children (t > 2.491, P < 0.05), except that of daytime sleepiness. The prevalence of sleep disturbance (CSHQ ≥ 41) was 89.6% in ASD children, which was more than that of the healthy children (76.8%) (χ² = 13.360, P < 0.001). The sleep problems in ASD children included bedtime resistance, sleep anxiety, sleep duration, sleep onset delay, parasomnias and sleep disordered breathing. ASD children were shorter in total bedtime, shorter in total sleep time, longer in sleep latency, longer in awake time and lower in sleep efficiency (|t| > 2.001, P < 0.05), compared with those of healthy children. For ASD children, the total bedtime negatively correlated with GDDS-language, PEP-3-expressive language, PEP-3-communication and PEP-3-maladaptive behaviors (r < -0.300, P < 0.05); the sleep efficiency negatively correlated with total score of CARS (r = -0.365, P < 0.05); sleep latency correlated with GDDS-social, PEP-3-cognitive, PEP-3-expressive language, PEP-3-receptive language, PEP-3-visual-motor imitation, PEP-3-characteristic verbal behaviors, PEP-3-communication, original score of ADOS, ADOS-social affect, and total score of CARS (|r| > 2.90, P < 0.05); and total awake time positively correlated with total score of CARS (r = 0.406, P < 0.05). ConclusionSleep disturbance is prevalent and various in preschool ASD children, and influence their social behaviors.

Objective To quantitatively analyze the risk indicators of re-introduction of imported malaria in China and their weighting coefficients, so as to investigate the difference in the contribution of risk indicators included in the current risk assessment framework for re-introduction of imported malaria in China to the risk assessment of re-introduction of imported malaria. Methods Publications pertaining to the risk assessment framework for re-introduction of imported malaria in China that reported the risk indicators and their weighting coefficients were retrieved in PubMed, Web of Science, CNKI, Wanfang Data, and VIP with terms of “malaria”, “re-introduction/re-transmission/re-establishment”, “risk assessment/risk evaluation/risk prediction” from the inception of the database through 3 August 2023, and literature search was performed in Google Scholar to ensure the comprehensiveness of the retrieval. Basic characteristics of included studies were extracted using pre-designed information extraction forms by two investigators, and data pertaining to risk indicators of re-introduction of imported malaria were cross-checked by these two investigators. The risk indicators included in the risk assessment framework for re-introduction of imported malaria in China and their weighting coefficients were visualized with the Nightingale’s rose diagrams using the software R 4.2.1, and the importance of risk indictors was evaluated with the frequency of risk indicators included in the risk assessment framework and the ranking of weighting coefficients of risk indicators. In addition, the capability of risk indicators screened by different weighting methods was compared by calculating the ratio of the maximum to the minimum of the weighting coefficients of the risk indicators screened by different weighting methods. Results A total of 2 138 publications were retrieved, and following removal of duplications and screening, a total of 8 publications were included in the final analysis. In these 8 studies, 8 risk assessment frameworks for re-introduction of imported malaria in China and 52 risk indicators of re-introduction of imported malaria were reported, in which number of imported malaria cases (n = 8) and species of malaria vectors were more frequently included in the risk assessment frameworks (n = 8), followed by species of imported malaria parasites (n = 6) and population density of local malaria vectors (n = 6), and species of local malaria vectors (n = 6), number of imported malaria cases (n = 5) and species of imported malaria parasites had the three highest weighting coefficients (n = 4). The weighting methods included expert scoring method, combination of expert scoring method and analytic hierarchy process, and combination of expert scoring method and entropy weight method in these 8 studies, and the ratios of the maximum to the minimum of the weighting coefficients of the risk indicators screened by the expert scoring method were 1.143 to 2.241, while the ratios of the maximum to the minimum of the weighting coefficients of the risk indicators screened by combination of the expert scoring method and analytic hierarchy process were 34.970 to 162.000. Conclusions Number of imported malaria cases, species of imported malaria parasites, species of local malaria vectors and population density of local malaria vectors are core indicators in the current risk assessment framework for re-introduction of imported malaria in China. Combination of the expert scoring method and analytic hierarchy process is superior to the expert scoring method alone for weighting the risk indicators.

OBJECTIVE To evaluate the cost -effectiveness of tislelizumab in the second -line treatment of advanced or metastatic esophageal squamous cell carcinoma （ESCC）in China .METHODS A three -state Markov model was constructed to assess the cost -effectiveness of tislelizumab versus chemotherapy in the second -line treatment of advanced or metastatic ESCC and programmed death receptor 1（PD-L1）positive patients . The cycle length of the model was 1 month，and the time horizon of the model was set as 10 years. The discount rate of cost and utility was 5%. One-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base -case analysis results . RESULTS The results of the base-case analysis showed that compared with chemotherapy ，the incremental cost -effectiveness ratio （ICER）of tislelizumab in the second-line treatment of advanced or metastatic ESCC and PD -L1-positive patients were 26 864.01 yuan/QALY and 37 510.07 yuan/QALY，respectively，which was much lower than 1 time per capita gross domestic product （GDP）in 2021（80 976 yuan）. Results of scenario analysis showed that the ICER was less than 1 times per capita GDP ，regardless of the chemotherapy regimens（paclitaxel，docetaxel or irinotecan ）used. With the extension of the simulation time limit ，the ICER of tirelizumab regimen gradually decreased ，and the reduction rate gradually E-mail：lishunping@sdu.edu.cn decreased，but they were all less than 1 time China ’s per capita GDP in 2021. The results of the one -way sensitivity analysis showed that the 3 parameters with the most significant impact on the ICER were progression -free survival of tislelizumab group ，price of tislelizumab ，and the proportion of patients receiving follow-up treatment in the tislelizumab group . The results of the probability sensitivity analysis showed that the probability of tislelizumab with cost -effectiveness in the treatment of advanced or metastatic ESCC patients and PD -L1-positive patients were 99.09% and 99.94%，respectively，when using 3 times per capita GDP as the willingness -to-pay threshold . CONCLUSIONS Tislelizumab has economic advantages over chemotherapy alone in the second -line treatment of advanced or metastatic ESCC patients.

Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.

Objective:The purpose of this study was to investigate the characteristics of viral pathogen spectrum and the epidemiological characteristics of each viral pathogen in hospitalized cases associated with severe acute respiratory infection (SARI) in Luohe City, Henan Province from 2017 to 2019.Methods:Based the SARI Case Surveillance Platform, SARI cases were collected in Central Hospital of Luohe City, Henan Province from November 2017 to February 2019. In the end, 783 SARI cases were included, whose throat swabs were taken within 24 h of admission, as well as their demographic characteristics, onset time, clinical characteristics and other information recorded. At the same time, viral identification was performed, and the age and time distribution of each virus were analyzed.Results:The age of 783 SARI cases shown as M ( P 25, P 75) was 3 (1, 5) years old, ranging from 1 month to 95 years old. Children under 5 years old were the majority (71.01%). The males (61.81%) were more than females (38.18%). Among the 783 SARI cases, a total of 9 kind of viruses were identified with 64.88% (508/783) of the throat swabs tested positive for at least one virus. The positive rate of influenza virus and human respiratory syncytial virus were both 20.18% (158 cases), which was the highest among all the detected respiratory virus. The co-infection rate was 15.84% (124/783), among which double infection was the most common, accounting for 85.48% (106/124) of the co-infected cases. And human respiratory syncytial virus, human rhinovirus and influenza virus were the most common pathogen in co-infection cases. Moreover, the viral positive rate was 68.71% in children aged 5 years and 63.27% in people aged 60-95 years. Influenza and human respiratory syncytial virus dominated in winter and spring, while human parainfluenza virus was the main infection in summer. Conclusion:Influenza virus and human respiratory syncytial virus were the main viruses in throat swabs of SARI cases from 2017 to 2019 in Luohe City, Henan Province. There were differences in the age and seasonal epidemiological characteristics of each virus.

Objective:To compare the clinical effects of 4 kinds of neurocutaneous perforator flap with vascular anastomosis for repair of hand and foot wounds.Methods:From January, 2005 to September, 2019, 112 patients with hand and foot wounds were treated, there were 78 cases of fingers, 11 cases of first web, 5 cases of palm, 6 cases of hand and 12 cases of foot. The defect area was 2.0 cm×1.5 cm-21.0 cm×12.0 cm. All 112 cases were repaired by neurocutaneous perforator flaps anastomosed with blood vessels. Types of flap were applied: Radial collateral artery perforator flap (with posterior cutaneous nerve of forearm) in 30 cases. The flap area was 5.0 cm×2.0 cm-13.0 cm×6.0 cm. Superficial peroneal artery flap (without superficial peroneal nerve) anastomosed with blood vessels in 15 cases. The flap area was 2.5 cm×2.0 cm-9.0 cm×6.0 cm. Lateral superficial sural artery perforator flap (with superior sural cutaneous nerve) in 26 cases. The flap area was 2.5 cm×1.8 cm-7.0 cm×5.0 cm. Peroneal artery perforator flap (with middle and lower sural nerve) in 41 cases. The flap was harvested with area of 2.5 cm×1.8 cm-23.0 cm ×14.0 cm to repair the wounds of feet, back of hands, first web, palm and fingers. CTA images were observed in 40 clinical patients, and the occurrence rate of radial collateral artery, superficial peroneal artery, superficial lateral sural artery, and peroneal artery were measured. Anastomosis cutaneous nerve in 97 cases, and no cutaneous nerve anastomosis 15 cases (superficial peroneal artery flap).Results:The peroneal artery perforator flap (41 cases) and radial collateral artery perforator flap (30 cases) were harvested. The incidence of perforator vessels was both 100%, and incidence of superficial sural artery was 80.8% (21/26 cases). In the other 19.2% (5/26 cases), the superficial medial sural artery was replaced by too thin vessels. The utilization rate of superficial peroneal artery was 60.0% (9/15 cases), the other 40.0% (6/15 cases) were converted to peroneal artery perforator flap. All flaps survived except 1 case of superficial perforator flap of lateral sural artery, which underwent necrosis at the distal end and healed after dressing change. One hundred and one cases were followed-up, including 90 cases for repairing soft tissue defects in hands and 11 cases in feet. The followed-up time ranged from 12 to 120 months, with an average of 36.6 months. There were 40 cases with excellent function, 45 cases with good function and 5 cases with fair function. There were 78 cases of cutaneous nerve anastomosis of hand flap, and the sensory function was above S 3 level. There were 12 cases without anastomosis of cutaneous nerve of hand flap, and the sensory function reached S 3 level in 3 cases and S 2 level in 9 cases. In 11 cases, the cutaneous nerve was anastomosed to repair the soft tissue defect of the foot, and the sensory function was above S 3 level. The radial collateral artery perforator flaps were relatively bulky and needed to be treated by fat removal. The other 3 kinds of three flaps were not bulky. Conclusion:The perforating vessels of peroneal artery and radial accessory artery have larger diameter and easy to harvest. The superficial peroneal artery and the lateral superficial sural artery are relatively small in caliber, especially the superficial peroneal artery. Among the 4 kinds of cutaneous nerve nutrient vascular flaps, the radial accessory artery perforator flap was the most bloated. Sensory nerve innervation flaps were found in the upper segment of lateral sural cutaneous nerve, posterior forearm cutaneous nerve and middle and lower segment of sural nerve. The superficial peroneal artery perforator flap was accompanied by superficial peroneal nerve that did not send cutaneous branches into the flap. The upper segment of superficial peroneal nerve was only a passing nerve.