ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.

Objective: To analyze the causes of abnormal blood agglutination caused by high-titer cold antibodies in blood donors from a serological perspective. Methods: The donor's blood type was identified using the tube method. Direct antiglobulin test (DAT), indirect antiglobulin test (IAT), and antibody titer detection were performed on the samples. Results: The blood type of the donor was type B, and the DAT was negative. No complement components were detected on the surface of the donor's red blood cells. The supernatant of the suspended red blood cells was clear without abnormal coloration, and the agglutinated clumps were intact and difficult to dissociate. The antibody was identified as an IgM-type anti-IH cold agglutinin. At 4℃, this antibody reacted with autologous red blood cells, adult group B red blood cells, adult group O red blood cells, cord blood group B red blood cells and cord blood group O red blood cells, with a stronger reaction intensity observed with group O cells than with B cells. The titers were 512, 128, 256, 32 and 128, respectively. Conclusion: High-titer anti-IH can cause abnormal agglutination of blood at low temperatures. During blood distribution and clinical use, the appearance of blood products shall be strictly inspected to prevent the release of non-conforming blood products.

AIM: To explore the factors influencing the efficacy of diabetic macular edema(DME)with conbercept and to construct a nomogram prediction model. METHODS:Retrospective analysis. Patients with DME admitted from January 2021 to October 2025 were selected. All patients received intravitreal conbercept injection once monthly for three consecutive months. Subjects were divided into a good response group and a poor response group according to the reduction in central macular thickness(CMT)at 3 mo after treatment. The clinical data of the patients were collected to analyze factors associated with poor response to conbercept therapy in patients with DME, and to construct a nomogram prediction model for identifying poor responders to conbercept treatment among DME patients.RESULTS:A total of 400 DME patients(400 eyes)were included in this study. The response group consisted of 312 patients(312 eyes), with 200 males and 112 females, with an average age of 64.85±5.13 y. The non-response group consisted of 88 patients(88 eyes), with 54 males and 34 females, with an average age of 65.14±4.93 y. There were no differences between the two groups in terms of gender, age, alcohol consumption, smoking status, duration of diabetes, edema classification, disease classification, low-density lipoprotein, HRF, ELM and/or EZ continuity interruption, and SRF(all P>0.05). However, there were differences in DR disease duration, pre-treatment BCVA, high-density lipoprotein, glycated hemoglobin, DRIL, and VMIA(all P<0.05). Multivariate Logistic regression analysis showed that DR disease duration ≥1 y(OR=2.351, 95%CI: 1.360-4.065), poor pre-treatment BCVA(OR=3.432, 95%CI: 1.581-6.988), high glycated hemoglobin(OR=1.656, 95%CI: 1.346-2.038), presence of DRIL(OR=3.115, 95%CI: 1.532-6.333), and presence of VMIA(OR=2.526, 95%CI: 1.445-4.415)were all risk factors for poor response to conbercept treatment in DME patients, while elevated high-density lipoprotein(OR=0.025, 95%CI: 0.004-0.163)was a protective factor for poor response to conbercept treatment in DME patients(P<0.05). ROC analysis showed that the area under the curve(AUC)of the nomogram model for predicting poor response to conbercept treatment in DME patients was 0.817(95%CI: 0.776-0.854), with a sensitivity of 73.86% and a specificity of 78.21%. When the threshold probability was >3%, the nomogram model for predicting poor response to conbercept treatment in DME patients was more favorable for all patient treatment plans. CONCLUSION:The nomogram prediction model constructed in this study is helpful for the clinical early identification of patients with DME who have a high risk of poor response to conbercept treatment, and can provide a reference for the early prevention of poor response to conbercept treatment.

ObjectiveTo observe the effect of rehabilitation robot training on abdominal muscles thickness and balance ability in children with hemiplegia. MethodsFrom October, 2024 to December, 2025, 58 children with hemiplegia were admitted to Beijing Bo'ai Hospital and randomly divided into control group (n = 29) and experimental group (n = 29). Both groups received conventional rehabilitation treatment, and the experimental group received rehabilitation robot training in addition, for four weeks. The thickness of bilateral external oblique, internal oblique and transversus abdominis, Berg Balance Scale (BBS) score, the time of Timed Up and Go Test (TUGT), the center of pressure (COP) ellipse area, and self-selected walking speed (SWS) and maximum walking speed (MWS) of 10-meter walk test were compared before and after training. ResultsThree cases dropped out in each group. After training, the thickness of the external oblique, internal oblique and transverse abdominis on the hemiplegic side increased significantly in the experimental group (|t| > 7.280, P < 0.001, Cohen's d = 1.43~2.01), and was better in the experimental group than in the control group (|t| > 2.895, P < 0.01, Cohen's d = 0.80~1.60); the BBS score increased in both groups (|t| > 6.667, P < 0.001, Cohen's d = 1.30~4.06), and was better in the experimental group than in the control group (t = -2.721, P < 0.01, Cohen's d = 0.75). The time of TUGT decreased in both groups (t > 5.790, P < 0.001, Cohen's d = 1.14~2.68), and was better in the experimental group than in the control group (t = 2.290, P < 0.05, Cohen's d = 0.63). The SWS and MWS increased in both groups (|Z| > 2.910, P < 0.01, r = 0.40~0.68), and were better in the experimental group than in the control group (|Z| > 2.912, P < 0.05, r = 0.40~0.45), and the differences remained significant after correction. ConclusionRehabilitation robot training can improve the thickness of external oblique, the internal oblique and transversus abdominis muscles on the hemiplegic side in children with hemiplegia, and improve their balance and walking functions.

Cervical cancer (CC) is the fourth leading cause of cancer-related deaths among women worldwide in 2022, and conventional treatment modalities offer limited efficacy for patients with advanced or recurrent disease. Natural killer (NK) cells are a subset of lymphocytes capable of non-specifically eliminating tumor cells and virus-infected cells without prior sensitization, and have emerged as a research focus in the field of cancer immunotherapy. However, the systematic elucidation and in-depth analysis are required in the dual regulatory mechanisms of NK cells within the cervical cancer microenvironment and the bottlenecks hindering their clinical translation. This article reviews the application of NK cell-based immunotherapy in CC, summarizes the mechanisms of action and therapeutic advances of NK cells in CC, identifies the major obstacles to current clinical translation, and proposes corresponding solutions.

OBJECTIVE To investigate the mechanism by which resveratrol improves renal injury in rats with uric acid nephropathy （UAN） through inhibition of the protein kinase R-like endoplasmic reticulum kinase （PERK）/eukaryotic translation initiation factor 2α （eIF2α） pathway.METHODS A UAN rat model was established via oral administration of adenine plus potassium oxonate， and the rats were divided into a UAN model group， a positive control group （allopurinol 10 mg/kg）， a resveratrol group （100 mg/kg）， and a resveratrol+tunicamycin group [resveratrol 100 mg/kg+tunicamycin （PERK activator） 1 mg/kg]. A control group （without modeling） was also established， with 6 rats in each group. Rats in each group were administered the corresponding drug solution and/or normal saline via gavage or intraperitoneal injection once daily for 28 consecutive days. The contents of renal function-related parameters （24-hour urinary total protein， and uric acid， creatinine and blood urea nitrogen in serum）， the levels of inflammation-related markers [interleukin-6 （IL-6）， IL-18， tumor necrosis factor-α （TNF-α）， IL-10， and nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）]， and pathological changes in renal tissue were determined， and the score for tubular damage， the score for inflammatory infiltration， and the degree of mesangial proliferation were assessed. The mRNA expressions of neutrophil gelatinase-associated lipocalin （NGAL） and kidney injury molecule-1 （KIM-1）， as well as the expressions of proteins associated with the PERK/eIF2α pathway， were measured in renal tissue from each group.RESULTS Compared with the control group， rats in the UAN model group exhibited marked tubular damage， inflammatory cell infiltration， and mesangial proliferation. The contents of renal function-related parameters， levels of IL-6， IL-18， TNF-α and NLRP3， scores for tubular damage and inflammatory infiltration， degree of mesangial proliferation， mRNA expressions of NGAL and KIM-1， and phosphorylation levels of PERK and eIF2α， as well as the expressions of activating transcription factor 4 and C/EBP homologous protein， were all significantly increased or upregulated， while IL-10 levels were significantly decreased （ P ＜0.05）. Compared with the UAN model group， the resveratrol group and the positive control group showed significant improvements in all of the aforementioned parameters （ P ＜0.05）. Tunicamycin could significantly reverse the beneficial effects of resveratrol on all quantitative parameters （ P ＜0.05）.CONCLUSIONS Resveratrol can reduce inflammatory responses in renal tissue of UAN rats， and improve tubular damage and renal function. These effects may be related to the inhibition of endoplasmic reticulum stress mediated by the PERK/eIF2α pathway.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

OBJECTIVES: The prevalence of overweight and obesity among children and adolescents continues to rise, becoming one of the most serious global public health issues of the 21st century. Given the differing growth and development environments between urban and rural children, associated risk factors also vary. This study aims to explore the distribution characteristics and influencing factors of overweight and obesity among urban and rural primary and secondary school students in Hunan Province, providing scientific evidence for targeted interventions. METHODS: A stratified, randomized cluster sampling method was used to select participants. A total of 197 084 students from primary and secondary schools across 14 prefectures in Hunan Province underwent physical examinations and questionnaire surveys. Population and spatial distribution characteristics of overweight and obesity were analyzed. Spatial distribution maps and spatial autocorrelation analyses were conducted using ArcGIS. Multivariate Logistic regression was used to identify influencing factors for overweight and obesity. RESULTS: The overall overweight and obesity rates among students in Hunan Province were 14.7% and 10.9%, respectively. Both rates were higher in urban areas than in rural counties (16.0% vs 13.9% for overweight; 12.1% vs 10.2% for obesity). Among both urban and rural students, boys had higher rates of overweight and obesity than girls. Higher-grade students had a higher overweight rate but a lower obesity rate than lower-grade students. In urban areas, the overweight and obesity rates of Han Chinese primary and secondary school students are lower than those of ethnic minority students (both P<0.05). In rural areas, the obesity rate of Han primary and secondary school students is lower than that of ethnic students (P<0.05). Across cities and prefectures, urban overweight and obesity rates ranged from 14.7% to 18.7% and 8.4% to 20.6% respectively, while rural rates ranged from 10.9% to 17.2% and 6.6% to 13.7% respectively. Spatial autocorrelation analysis revealed high-value clusters of overweight/obesity in urban areas of Changde and Zhangjiajie, and in rural areas of Loudi, Huaihua, and Shaoyang. Multivariate Logistic regression showed that gender, school stage, ethnicity, frequency of fresh vegetable intake, and sleep duration were associated with overweight and/or obesity in both urban and rural students. In urban students, frequency of fried food and fresh fruit intake, breakfast habits, physical activity on weekdays and holidays, and screen time on computers were also significant. In rural students, TV viewing time and sedentary duration were additional relevant factors. CONCLUSIONS The situation of overweight and obesity among primary and secondary school students in Hunan Province remains concerning. Greater attention should be paid to regions with high-value clusters of overweight/obesity, and targeted interventions should be developed based on urban-rural differences in influencing factors.
Humans ; China/epidemiology* ; Adolescent ; Male ; Female ; Rural Population/statistics & numerical data* ; Child ; Overweight/epidemiology* ; Students/statistics & numerical data* ; Urban Population/statistics & numerical data* ; Risk Factors ; Prevalence ; Obesity/epidemiology* ; Surveys and Questionnaires ; Pediatric Obesity/epidemiology* ; Schools

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.