ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

ObjectiveMultiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS); however, its underlying neurological pathogenic mechanisms remain incompletely understood. Endogenous formaldehyde (FA), a metabolic byproduct of methylation-demethylation cycles, has recently been implicated in neurotoxicity, oxidative damage, and cognitive impairment. This study aimed to investigate whether excessive FA contributes to myelin sheath demyelination in mice and to evaluate the protective effects and mechanisms of two FA-elimination strategies: sodium bisulfite (NaHSO₃), a classical FA scavenger, and polyethylene glycol-modified astaxanthin nanoparticles (PEG-ATX@NPs), a brain-targeted nano-antioxidant formulation. MethodsA chronic demyelination model was established by feeding female C57BL/6J mice a diet containing 0.2% cuprizone (CPZ) for four weeks, followed by a two-week intervention period. Eighty mice were randomly assigned to four groups: NS (normal saline), CPZ+NS, CPZ+NaHSO₃, and CPZ+PEG-ATX@NPs. Behavioral tests, including open-field, Y-maze, and pole-climbing assays, were conducted to assess locomotor activity, motor coordination, and working memory. FA levels in serum, corpus callosum, and spinal cord were measured using an Na-FA fluorescent probe and quantified via in vivo and ex vivo fluorescence imaging. Neuroinflammatory responses were evaluated by measuring TNF-α, IL-1β, and IL-6 levels using ELISA, while oxidative stress was assessed by reactive oxygen species (ROS) fluorescence intensity. Demyelination was examined via Luxol fast blue staining, and microglial activation was analyzed by Iba1 immunofluorescence. Correlation analyses were performed to explore relationships among FA levels, inflammatory cytokines, ROS intensity, and behavioral parameters. ResultsCompared with the NS group, mice in the CPZ+NS group exhibited significant weight loss, impaired motor coordination and memory, and markedly reduced myelin regeneration (P<0.05). FA levels and pro-inflammatory cytokines were significantly elevated in serum, corpus callosum, and spinal cord (P<0.05). FA-associated fluorescence in brain and spinal tissues, as well as ROS intensity across all tissues examined, also increased substantially (P<0.05). CPZ treatment induced pronounced microglial activation and severe demyelination in the corpus callosum (P<0.01). Both NaHSO₃ and PEG-ATX@NPs effectively reduced FA accumulation in the brain and spinal cord, attenuated demyelination, suppressed microglial activation, decreased inflammatory cytokine levels, and improved motor and cognitive performance. These results confirm that CPZ induced severe demyelination accompanied by oxidative stress, neuroinflammation, and abnormal FA accumulation. Following intervention with either NaHSO₃ or PEG-ATX@NPs, endogenous FA levels in the CNS were substantially reduced. Both treatments alleviated demyelination and significantly decreased the number of activated microglia. Levels of TNF-α, IL-1β, and IL-6 in serum, corpus callosum, and spinal cord were downregulated. Behavioral performance improved significantly, as evidenced by enhanced locomotor activity, better coordination, and improved memory function. These findings indicate that both FA-scavenging agents mitigate CPZ-induced biochemical and behavioral abnormalities. ConclusionThis study demonstrates that excessive endogenous FA is closely associated with cognitive impairment, inflammatory dysregulation, and demyelination in a CPZ-induced chronic demyelination mouse model. Clearing abnormally elevated FA effectively reduces neuroinflammation, suppresses microglial overactivation, decreases oxidative stress, and alleviates demyelination, ultimately improving motor and cognitive outcomes in mice. These results suggest that targeting endogenous FA represents a promising therapeutic strategy for MS and other demyelinating disorders. Further investigations are warranted to explore the long-term safety, dosage optimization, and molecular pathways involved in FA-mediated neurotoxicity.

AIM: To investigate the current incidence of retinopathy of prematurity(ROP)in Sichuan Province and analyze its risk factors, providing a scientific basis for establishing and improving the regional ROP screening and prevention system.METHODS: A retrospective study was conducted on premature infants who underwent fundus screening at the Departments of Ophthalmology and Neonatology of Sichuan Provincial Maternity and Child Health Care Hospital from January 20, 2017 to February 10, 2025. The incidence of ROP was calculated. The patients were divided into ROP group and non-ROP group according to whether ROP occurred, and the clinical characteristics of the two groups were compared. Multivariate Logistic regression was used to analyze risk factors for ROP.RESULTS:This study included a total of 861 premature infants, with 445 males(51.7%)and 416 females(48.3%).ROP occurred in 166 cases, with an incidence rate of 19.3%, and the non-ROP group consisted of 695 cases. The mean gestational age of the ROP and non-ROP groups was 30.24±2.20 and 33.06±1.90 wk(P<0.01), while the mean birth weight was 1438.94±389.66 and 1977.32±438.68 g(P<0.01). By comparing the clinical data of the two groups of preterm infants, the following factors were found to be associated with the occurrence of ROP: younger gestational age, low birth weight, history of oxygen therapy, respiratory distress syndrome, intracranial hemorrhage, neonatal anemia, bronchopulmonary dysplasia, patent ductus arteriosus, and sepsis(all P<0.01). Multivariate Logistic regression analysis revealed that gestational age(OR=0.685,95%CI:0.592-0.792,P<0.01), birth weight(OR=0.999,95%CI:0.998-0.999,P<0.01), and respiratory distress syndrome(OR=2.312,95%CI:1.313-4.070,P<0.01)were risk factors for ROP. Gestational age had the greatest impact.The younger the gestational age at birth, the higher the risk of ROP.CONCLUSION:The incidence of ROP in Sichuan Province is relatively high compared to multicenter results from China. Significant risk factors include younger gestational age, low birth weight, and respiratory distress syndrome. Screening criteria should be formulated based on the local incidence of ROP, and a screening, prevention, and treatment system for ROP should be established and improved.

OBJECTIVE: To explore the early changes in various liver function indicators in critically injured trauma patients assessed by intelligent calculation method, aiming to develop more advantageous diagnostic and treatment strategies for traumatic liver injury. METHODS: A retrospective study was conducted. Critically injured trauma patients [injury severity score (ISS) ≥ 16, age > 18 years old] admitted to the Emergency Medical Center of Tianjin Fifth Central Hospital from January 1, 2022, to December 1, 2023 were enrolled. ISS score and acute physiology and chronic health evaluation II (APACHE II) assessed by intelligent calculation method were collected upon patient admission to the emergency medical center. Trends in liver function indicators in fasting venous serum were analyzed at 6, 24 and 72 hours after admission, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), albumin (ALB), total bilirubin (TBil), prothrombin time (PT). Patients were grouped based on APACHE II scores into those with APACHE II < 15 and APACHE II ≤ 15, and liver function indicators within 6 hours of admission were compared between the two groups. RESULTS: A total of 112 critically injured trauma patients were included, with 83 males and 29 females, an average age of (47.78±14.84) years old. The median ISS score was 21.0 (18.0, 26.0). The most common cause of injury for critically injured trauma patients was road traffic accidents (68 cases, accounting for 60.71%), followed by falls from heights, compression injuries, heavy object injuries, knife stabs, and explosion injuries. The most common injured areas was the limbs and pelvis (97 cases, accounting for 86.61%), followed by chest injuries, surface skin and soft tissue injuries, abdominal and pelvic organ injuries, head injuries, and facial injuries. The proportion of elevated LDH, AST, and ALT within 6 hours of admission was 77.68%, 79.46%, and 52.68%, respectively, while the proportion of decreased ALB was 75.89%, the abnormal rates of ALP, GGT, TBil, and PT were all below 50%. The ALT and AST levels of patients at 24 hours and 72 hours after admission were significantly lower than those at 6 hours after admission [ALT (U/L): 37.0 (22.0, 66.0), 31.0 (21.2, 52.0) vs. 41.0 (25.0, 71.0), AST (U/L): 55.5 (30.0, 93.5), 40.0 (27.0, 63.2) vs. 69.5 (39.0, 130.8), all P < 0.05]. There was no statistically significant difference in ISS score between APACHE II > 15 group (45 cases) and APACHE II ≤ 15 group [67 cases; 21.0 (18.5, 26.5) vs. 20.0 (17.0, 22.0), P > 0.05]. Nevertheless, compared with patients with APACHE II ≤ 15, patients with APACHE II > 15 have a higher abnormality rate of ALT and AST within 6 hours of admission [ALT abnormal rate: 66.44% (29/45) vs. 44.78% (30/67), AST abnormal rate: 93.33% (42/45) vs. 70.15% (47/67), both P < 0.05], and the levels of ALT and AST were higher [ALT (U/L): 56.0 (30.0, 121.0) vs. 35.0 (21.0, 69.0), AST (U/L): 87.0 (48.0, 233.0) vs. 52.0 (31.0, 117.0), both P < 0.05]. CONCLUSIONS Severe trauma patients frequently exhibit a high incidence of reversible early liver function impairment. Based on intelligent calculation method, the utilization of both the ISS and APACHE II scores demonstrates a distinct advantage in the assessment of their early liver injury.
Humans ; Retrospective Studies ; Liver/physiopathology* ; Risk Assessment ; APACHE ; Wounds and Injuries ; Adult ; Injury Severity Score ; Male ; Middle Aged ; Female ; Liver Function Tests ; Alanine Transaminase/blood* ; Young Adult ; Aspartate Aminotransferases/blood*

OBJECTIVE: To explore clinical efficacy of different technical combinations in treating ischemic diabetic foot (DF). METHODS: A retrospective analysis was conducted on 35 patients with DF who were treated with vascular interventional opening technique, periosteal distraction technique and bone cement coverage technique from January 2024 to November 2024. They were divided into comprehensive group and periosteal distraction group according to whether the vascular interventional opening technique was used in combination or not. There were 5 patients in comprehensive group, including 4 males and 1 female, aged from 59 to 73 years old with an average of (64.40±5.46) years old;the duration of diabetes ranged from 0.17 to 30.00 years with an average of (14.63±12.02) years;the courses of DF ranged from 30 to 150 days with an average of (84.00±61.48) days;2 patients were grade 2, 2 patients were grade 3, and 1 patient was grade 4 according to Wagner classification;combined vascular interventional opening, periosteal distraction and bone cement coverage surgery for treatment. There were 30 patients in periosteal stretch group, including 22 males and 8 females, aged from 58 to 86 years old with an average of (72.63±7.84) years old;the duration of diabetes was 10.00 (6.75, 16.75) years;the courses of DF was 30.00 (15.00, 37.50) days;14 patients were grade 2, 11 patients were grade 3, and 5 patients were grade 4 according to Wagner classification; combined periosteal distraction and bone cement coverage surgery for treatment. Changes of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT), toe skin temperature, peripheral capillary oxygen saturation (SpO₂), and visual analogue scale (VAS) for pain were compared between two groups before operation and 1 week after operation. The number of operations, healing period, healing number, toe amputation number, preoperative fever situation and the number of complications were compared between two groups. RESULTS: Both groups were followed up for at least 6 months. There were no statistically significant differences in the number of operations, healing period, toe amputation rate, wound healing rate and complications between two groups (P>0.05). Before operation, the toe skin temperature of comprehensive group (26.98±0.88) ℃ was lower than that of periosteal distraction group (28.17±1.45) ℃, and the difference was statistically significant (P<0.05);while there were no statistically significant difference in CRP, IL-6, PCT, toe SpO2 and VAS between two groups (P>0.05). At 1 week after operation, IL-6, toe skin temperature, toe SpO₂ and VAS in comprehensive group were 12.29(7.92, 22.15) pg·ml-1, (36.02±0.23) ℃, (95.80±0.84) % and(1.40±0.55) respectively, while those in periosteal distraction group were 5.49(4.36, 7.45) pg·ml^-1, (31.36±1.57) ℃, (84.53±6.38) %, (2.20±0.81);and there were statistically significant differences between two groups(P<0.05). CRP, IL-6 and VAS at 1 week after operation in both groups were decreased compared with those before operation, and the differences were statistically significant(P<0.05). The toe skin temperature and SpO₂ were increased compared with those before operation, and the differences were statistically significant(P<0.001). CONCLUSION The multi-technique combination therapy, including vascular interventional opening technique, periostealdistraction technique and bone cement covering technique, could protect each other, enhance efficacy, effectively promote the wound healing of ischemic diabetic foot ulcer, and reduce the toe amputation rate. For moderate to severe ischemic DF, the combined use of periosteal distraction and bone cement coverage techniques has a satisfactory effect. For extremely severe ischemic DF with inflow tract lesions, vascular interventional opening techniques need to be added.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/surgery* ; Retrospective Studies ; Aged, 80 and over ; Ischemia/surgery* ; Interleukin-6/metabolism*

OBJECTIVE: To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation, joint destruction, and functional impairment. Angiogenesis plays a key role in the pathological progression of RA with dysfunction of endothelial cells to promote synovial inflammation, sustain pannus formation, subsequently leading to joint damage. Colquhounia Root Tablets (CRT), a Chinese patent drug, has shown a satisfying clinical efficacy in treating RA, while the underlying mechanism by which CRT inhibits RA-associated angiogenesis remains unclear. In this study, we applied a research approach combining transcriptomic data analysis, bio-network mapping, and in vivo and in vitro experiments to explore the molecular mechanisms of CRT in suppressing angiogenesis in RA. Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences (ratification number: IBTCMCACMS21-2307-06). Network analysis identified that key genes such as nucleotide-binding oligomerization domain-containing protein 2 (NOD2), SMAD family member 3 (SMAD3), and vascular endothelial growth factor A (VEGFA) significantly enriched in pathways related to NOD-like receptor signaling and VEGF signaling, indicating that CRT may inhibit angiogenesis by regulating vascular endothelial cell function with modulating angiogenesis-related pathways. In vivo data showed that CRT significantly reduced the positive expression of CD31 and VEGF in the ankle joint of adjuvant-induced arthritis (AIA) rats. In vitro data further confirmed that CRT effectively inhibited VEGF-induced migration, invasion, and tube formation in HUVECs, while significantly reduced the expression of angiogenesis-related factors VEGF/CD31/Ang-1, as well as the positive expression of VEGF and CD31 in HUVECs. Furthermore, CRT markedly decreased the protein expression of NOD2, VEGFA, and SMAD3. In conclusion, these findings indicate that CRT may inhibit the RA-related angiogenesis by targeting the NOD2/SMAD3/VEGF signaling axis to improve endothelial cell function, enriching the scientific connotation of CRT in inhibiting pathological angiogenesis in RA and also offer new insights for clinical prevention and treatment of RA.

This study was a single-center cross-sectional investigation aimed at identifying risk factors for cognitive dysfunction in patients undergoing maintenance hemodialysis (MHD), with the goal of providing a basis for improving patient prognosis. Patients receiving MHD in the Blood Purification Center of Hainan Provincial People's Hospital from June 1 to June 30, 2023, were enrolled. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and potential risk factors for cognitive impairment were analyzed by using Logistic regression. A total of 278 patients were included, 69 patients (24.8%) of whom had cognitive impairment. Multivariate Logistic regression analysis indicated that the history of cerebrovascular disease ( OR=3.109, 95% CI 1.310-7.378, P=0.010), old age ( OR=1.077, 95% CI 1.040-1.115, P<0.001), low dialysis frequency ( OR=0.270, 95% CI 0.120-0.606, P=0.001), low academic qualification (using college/university as the control group: primary school group OR=26.960, 95% CI 7.519-96.673, P<0.001; Junior high school/technical secondary school group OR=4.264, 95% CI 1.330-13.650, P=0.015; High school group OR=9.554, 95% CI 2.861-31.904, P<0.001), high β2-microglobulin ( OR=1.609, 95% CI 1.044-2.480, P=0.031) and high C-reactive protein/albumin ( OR=2.672, 95% CI 1.226-5.826, P=0.013) were independent risk factors for cognitive impairment in MHD patients.