As China accelerates its efforts in deep space exploration and long-duration space missions, including the operationalization of the Tiangong Space Station and the development of manned lunar missions, safeguarding astronauts’ physiological and cognitive functions under extreme space conditions becomes a pressing scientific imperative. Among the multifactorial stressors of spaceflight, microgravity emerges as a particularly potent disruptor of neurobehavioral homeostasis. Dopamine (DA) plays a central role in regulating behavior under space microgravity by influencing reward processing, motivation, executive function and sensorimotor integration. Changes in gravity disrupt dopaminergic signaling at multiple levels, leading to impairments in motor coordination, cognitive flexibility, and emotional stability. Microgravity exposure induces a cascade of neurobiological changes that challenge dopaminergic stability at multiple levels: from the transcriptional regulation of DA synthesis enzymes and the excitability of DA neurons, to receptor distribution dynamics and the efficiency of downstream signaling pathways. These changes involve downregulation of tyrosine hydroxylase in the substantia nigra, reduced phosphorylation of DA receptors, and alterations in vesicular monoamine transporter expression, all of which compromise synaptic DA availability. Experimental findings from space analog studies and simulated microgravity models suggest that gravitational unloading alters striatal and mesocorticolimbic DA circuitry, resulting in diminished motor coordination, impaired vestibular compensation, and decreased cognitive flexibility. These alterations not only compromise astronauts’ operational performance but also elevate the risk of mood disturbances and motivational deficits during prolonged missions. The review systematically synthesizes current findings across multiple domains: molecular neurobiology, behavioral neuroscience, and gravitational physiology. It highlights that maintaining DA homeostasis is pivotal in preserving neuroplasticity, particularly within brain regions critical to adaptation, such as the basal ganglia, prefrontal cortex, and cerebellum. The paper also discusses the dual-edged nature of DA plasticity: while adaptive remodeling of synapses and receptor sensitivity can serve as compensatory mechanisms under stress, chronic dopaminergic imbalance may lead to maladaptive outcomes, such as cognitive rigidity and motor dysregulation. Furthermore, we propose a conceptual framework that integrates homeostatic neuroregulation with the demands of space environmental adaptation. By drawing from interdisciplinary research, the review underscores the potential of multiple intervention strategies including pharmacological treatment, nutritional support, neural stimulation techniques, and most importantly, structured physical exercise. Recent rodent studies demonstrate that treadmill exercise upregulates DA transporter expression in the dorsal striatum, enhances tyrosine hydroxylase activity, and increases DA release during cognitive tasks, indicating both protective and restorative effects on dopaminergic networks. Thus, exercise is highlighted as a key approach because of its sustained effects on DA production, receptor function, and brain plasticity, making it a strong candidate for developing effective measures to support astronauts in maintaining cognitive and emotional stability during space missions. In conclusion, the paper not only underscores the centrality of DA homeostasis in space neuroscience but also reflects the authors’ broader academic viewpoint: understanding the neurochemical substrates of behavior under microgravity is fundamental to both space health and terrestrial neuroscience. By bridging basic neurobiology with applied space medicine, this work contributes to the emerging field of gravitational neurobiology and provides a foundation for future research into individualized performance optimization in extreme environments.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired motility of cilia and flagella. Mutations in cilia- and flagella-associated protein 300 ( CFAP300 ) are associated with human PCD and male infertility; however, the underlying pathogenic mechanisms remain poorly understood. In a consanguineous Chinese family, we identified a homozygous CFAP300 loss-of-function variant (c.304delC) in a proband presenting with classical PCD symptoms and severe sperm abnormalities, including dynein arm deficiency and acrosomal malformation, as confirmed by transmission electron microscopy (TEM). Histological analysis revealed multiple morphological abnormalities of the sperm flagella in CFAP300 -mutant individual, whereas immunofluorescence demonstrated markedly reduced CFAP300 expression in the spermatozoa of the proband. Furthermore, tandem mass tag (TMT)-based quantitative proteomics showed that the CFAP300 mutation reduced key spermatogenesis proteins (e.g., sperm flagellar 2 [SPEF2], solute carrier family 25 member 31 [SLC25A31], and A-kinase anchoring protein 3 [AKAP3]) and mitochondrial ATP synthesis factors (e.g., SLC25A31, cation channel sperm-associated 3 [CATSPER3]). It also triggered abnormal increases in autophagy-related proteins and signaling mediator phosphorylation. These molecular alterations are likely to contribute to progressive deterioration of sperm ultrastructure and function. Notably, successful pregnancy was achieved via intracytoplasmic sperm injection (ICSI) using the proband's sperm. Overall, this study expands the known CFAP300 mutational spectrum and offers novel mechanistic insights into its role in spermatogenesis.
Humans ; Male ; Infertility, Male/pathology* ; Acrosome/pathology* ; Sperm Tail/pathology* ; Pedigree ; Spermatozoa ; Adult ; Loss of Function Mutation ; Ciliary Motility Disorders/genetics* ; Spermatogenesis/genetics* ; Female

OBJECTIVE: To investigate the clinical characteristics, curative effect and prognostic factors of patients with multiple myeloma (MM) complicated with light chain myocardial amyloidosis (AL-CA). METHODS: The data of 38 patients diagnosed with MM complicated with AL-CA in our hospital from January 2018 to December 2023 were retrospectively analyzed, and the data were comprehensively screened by multiple methods such as positive two-dimensional spot tracking echocardiography (2D-STE). Survival analysis was performed using the Kaplan-Meier method. Cox regression models were used to screen for independent prognostic factors. RESULTS: Among the 38 MM patients with AL-CA, 23 were male and 15 were female, with a median age of 60(50,75) years. The 1-year survival rate was 71.05%. Patients who underwent transplantation had significantly better survival outcomes than those who did not (P < 0.01). Additionally, the median survival time of patients with all-negative FISH results at the first visit was statistically different compared to patients with other mutations (P < 0.05). Multivariate Cox regression analysis showed that all negative FISH results at the first visit and the absence of autologous hematopoietic stem cell transplantation (ASCT) were not independent risk factor for the prognosis of patients with MM and AL-CA (P >0.05). CONCLUSION ASCT may improve the prognosis of MM patients with AL-CA, and negative FISH results may indicate poor prognosis, but the results still need to be verified by larger samples.
Humans ; Multiple Myeloma/complications* ; Retrospective Studies ; Aged ; Female ; Male ; Middle Aged ; Prognosis ; Hematopoietic Stem Cell Transplantation ; Amyloidosis/complications* ; Survival Rate ; Proportional Hazards Models

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia. However, the regulatory mechanisms governing this circuit necessitate further elucidation. We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin (5-HT) facilitation system on spinal PKCγ neurons. Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_2C receptors, disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia. Inhibiting spinal 5-HT_2C receptors restored the feedforward inhibitory circuit, effectively preventing neuropathic allodynia. These insights offer promising therapeutic targets for neuropathic allodynia management, emphasizing the potential of spinal 5-HT_2C receptors as a novel avenue for intervention.
Animals ; Neuralgia/physiopathology* ; Protein Kinase C/metabolism* ; Receptor, Serotonin, 5-HT2C/metabolism* ; Hyperalgesia/physiopathology* ; Mice, Transgenic ; Mice ; Spinal Cord/metabolism* ; Serotonin/metabolism* ; Male ; Neurons/metabolism* ; Mice, Inbred C57BL

Acute pancreatitis (AP) is a severe inflammatory disease characterized by self-digestion of pancreatic tissue and inflammatory responses. Recent studies have revealed a close connection between gut microbiota and AP. The gut microbiota community, a complex ecosystem composed of trillions of microorganisms, is closely associated with various physiological activities of the host, including metabolic processes, immune system regulation, and intestinal structure maintenance. However, in patients with AP, dysbiosis of the gut microbiota are believed to play a key role in the occurrence and progression of the disease. This dysbiosis not only impairs the integrity of the intestinal barrier, but may also exacerbate inflammatory responses through multiple mechanisms, thereby affecting the severity of the disease and patient' clinical prognosis. This article reviews the mechanisms of action of gut microbiota in AP, explores how gut microbiota dysbiosis affects disease progression, and evaluates current clinical treatment methods to regulate intestinal flora, including probiotic supplementation, fecal microbiota transplantation, antibiotic therapy, and early enteral nutrition. In addition, this article discusses the efficacy and safety of the aforementioned therapeutic approaches, and outlines future research directions, aiming to provide novel perspectives and strategies for the diagnosis, treatment and prognostic evaluation of AP. Through in-depth understanding the interaction between gut microbiota and AP, it is expected that more precise and personalized therapeutic regimens will be developed to improve patients' quality of life and clinical outcomes.
Humans ; Gastrointestinal Microbiome ; Dysbiosis ; Pancreatitis/microbiology* ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use* ; Acute Disease ; Anti-Bacterial Agents/therapeutic use* ; Enteral Nutrition

Objective:To analyze the clinical characteristics of the Chikungunya fever outbreak in Shunde District, Foshan City, Guangdong Province in July 2025 and the risk factors associated with delayed viral RNA clearance.Methods:A total of 562 patients with Chikungunya fever admitted to three designated hospitals in Shunde District from July 10 to 30, 2025 were enrolled. Demographic data, clinical manifestations, and laboratory findings were collected. Patients were categorized into four age groups including minors (<18 years), young adults (18 to 39 years), middle-aged adults (40 to 64 years) and elderly adults (≥65 years). The differences of clinical characteristics among these age groups were analyzed. Intergroup comparisons were performed using chi-square test, one-way analysis of variance, or Kruskal-Wallis H test. Pairwise comparisons between groups were conducted using the Bonferroni or Games-Howell or Dunn method. Binary logistic regression was employed to analyze risk factors associated with delayed viral RNA clearance (>7 days). Results:The mean age of the 562 enrolled Chikungunya fever patients was (44.8±21.3) years. Fever, arthralgia and rash were the three core symptoms, with incidence rates of 87.5% (492/562), 88.4%(497/562) and 69.6%(391/562), respectively. At discharge, only 54.1%(304/562) of patients achieved complete symptom resolution, while 26.5%(149/562) still had arthralgia and 36.1%(203/562) had residual rash. Significant differences were observed among age groups in the incidence of fever ( χ2=9.43, P=0.024), peak body temperature ( F=6.54, P<0.001), incidence of arthralgia ( χ2=26.89, P<0.001), duration of arthralgia ( F=12.68, P=0.001), incidence of rash ( χ2=68.99, P<0.001), rate of residual rash at discharge ( χ2=32.37, P<0.001), lymphocyte count ( F=12.94, P<0.001), platelet count ( F=14.95, P<0.001), and C-reactive protein levels (CRP) ( H=94.18, P<0.001). Further pairwise comparisons revealed that compared to the middle-aged and elderly groups, the minor group had a higher incidence of fever and a lower incidence of arthralgia, and the duration of arthralgia was shorter than the elderly group (all P<0.008 3). Compared with the other three groups, the elderly group had lower incidence and residual rate of rash, and lower platelet counts (all P<0.008 3), and higher levels of CRP (all P<0.05). The elderly group had lower lymphocyte counts compared to the minor and young adult groups (both P<0.05). Significant differences were found among age groups in the time to viral RNA clearance ( F=5.77, P=0.003) and length of hospital stay ( F=11.64, P<0.001), with the elderly group having significantly longer duration for both compared to the other three groups (all P<0.05). Multivariate analysis showed that advanced age (odds ratio ( OR)=1.049, 95% confidence interval ( CI) 1.015 to 1.083), longer duration of fever ( OR=1.529, 95% CI 1.086 to 2.155) and longer duration of arthralgia ( OR=1.927, 95% CI 1.318 to 2.817) were independent risk factors for delayed viral RNA clearance (all P<0.05). Conclusions:Patients with Chikungunya fever in Shunde District primarily present with fever, arthralgia and rash. The incidence and characteristics of these three core symptoms show age-related variations. Elderly patients and those with longer durations of fever or arthralgia are more likely to experience delayed viral clearance.

Objective:To establish a three-dimensional navigation process for design and resection of perforator flaps based on multi-detector computed tomography angiography (MDCTA) and to explore its clinical application effects.Methods:This study was a retrospective observational study. From January 2021 to October 2023, 7 patients and 6 patients with post-traumatic skin and soft tissue defects in extremity and conformed to the inclusion criteria were admitted to the Affiliated Hospital of Jiangsu University and Wuxi No. 9 People's Hospital, respectively. There were 8 males and 5 females, aged 21 to 68 years. Nine patients had wounds on the hand and 4 patients had wounds on the foot. The wound area after debridement ranged from 8.0 cm×6.0 cm to 18.0 cm×17.0 cm. Through the three-dimensional navigation process based on MDCTA, 14 perforator flaps were designed and resected, including 11 free anterolateral thigh perforator flaps and 3 pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain, with flap size ranging from 9.0 cm×6.0 cm to 20.0 cm×15.0 cm. Six wounds in the flap donor sites were directly sutured, and eight wounds in the flap donor sites were transplanted with skin grafts. The consistency of the location, type, and source of the perforators was compared between the preoperative navigation display and actual intraoperative detection. Immediately after surgery, the coverage of wound by the flap was evaluated according to the self-made criteria. The postoperative flap survival was observed. The occurrence of complications was observed during follow-up. At the last follow-up, the appearance of the flaps was observed, the blood supply of the flaps and the hand function of the 9 patients with hand trauma were evaluated according to the trial standards for evaluation of partial function of upper extremity by the Hand Surgery Society of Chinese Medical Association, and the foot function of the 4 patients with foot trauma was assessed using the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Scoring System.Results:The location, type, and source of the perforators displayed in preoperative navigation were consistent with the actual intraoperative detection. Immediately after surgery, the coverage of the wounds by 11 flaps was rated as excellent, and that of 3 flaps was rated as moderate. Postoperatively, 13 flaps survived completely, and 1 flap had partial necrosis, which healed after a full-thickness skin grafting from the thigh. Patients were followed up for 4 to 24 months postoperatively, one patient developed a hematoma under the flap, and one patient had local infection. At the last follow-up, the flaps of all patients were good in color and texture, and 5 patients with bloated flaps post operation had good appearance after thinning surgery; the blood supply was excellent in 12 flaps and was good in 2 flaps; among patients with hand trauma, the hand function was rated as excellent in 2 cases, good in 4 cases, and poor in 3 cases; among patients with foot trauma, the foot function was rated as excellent in 3 cases and good in 1 case.Conclusions:The three-dimensional navigation process for design and resection of perforator flaps based on MDCTA realizes precise evaluation of perforator vessels in flap donor sites and skin and soft tissue defects in the recipient sites. Guided by the three-dimensional navigation process, the application of free anterolateral thigh perforator flaps and pedicled peroneal artery perforator flaps with sural nerve nutritional vessel chain in repairing skin and soft tissue defects in extremity realizes precise surgery, reducing flap donor site injury and achieving excellent clinical outcomes.

Objective:To observe the diuretic effects of Zhuling Decoction on mice with adriamycin nephropathy (ADRN); To explore its mechanism.Methods:Totally 32 SPF male C57BL/6 mice were divided into a blank group of 7 mice and a model group of 25 mice using a random number table method. ADRN model was prepared by single tail vein injection of 0.01 g/kg of amphotericin. Two weeks later, the successfully modeled mice were divided into a model group (7 mice), a furosemide group (8 mice), and a Zhuling Decoction group (8 mice). The blank group and model group mice were given equal volumes of injection water by gavage. The furosemide group was given 2.6 mg/kg of furosemide by gavage, and the Zhuling Decoction group was given 6.5 g/kg of Zhuling Decoction by gavage, once a day, for 8 consecutive weeks. Changes in body weight and urine output of mice were observed. A biochemical analyzer was used to detect 24-hour urinary protein quantification and blood potassium and SCr levels in mice. HE staining was used to observe pathological changes in mouse kidneys, and immunohistochemistry and Western blot were used to detect the homology of cyclin dependent kinase 18 (CDK18), STIP1, and the expressions of U-box protein 1 (STUB1) and aquaporin 2 (AQP2) in mouse kidney tissue cells.Results:Compared with the model group, both the furosemide and Zhuling Decoction groups exhibited increased 24-hour urine output ( P<0.05); compared with the model group and furosemide group, Zhuling Decoction group showed reduced average optical density values and protein expressions of CDK18 and AQP2 ( P<0.05) and increased STUB1 average optical density value and protein expression ( P<0.05). Conclusion:Zhuling Decoction can increase 24-hour urine output in ADRN mice, and the mechanism may be related to down-regulation of CDK18 and AQP2 protein expressions and up-regulation of STUB1 protein expression, thereby modulating the CDK18/STUB1/AQP2 pathway and reducing water reabsorption.