1.The Regulatory Mechanisms of Dopamine Homeostasis in Behavioral Functions Under Microgravity
Xin YANG ; Ke LI ; Ran LIU ; Xu-Dong ZHAO ; Hua-Lin WANG ; Lan-Qun MAO ; Li-Juan HOU
Progress in Biochemistry and Biophysics 2025;52(8):2087-2102
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.
2.Clinical efficacy of camrelizumab combined with apatinib versus camrelizumab combined with chemotherapy regimens as first-line treatment for advanced gastric cancer
Ran JU ; Qi MIAO ; Jun YANG ; Yonggui WANG ; Xiangning DONG
China Pharmacy 2025;36(18):2307-2311
OBJECTIVE To compare the clinical efficacy and safety of camrelizumab combined with apatinib versus camrelizumab combined with chemotherapy as first-line treatment for advanced gastric cancer. METHODS A prospective randomized controlled trial was conducted, enrolling 99 patients with advanced gastric cancer admitted to the Chuzhou First People’s Hospital from March 2022 to December 2024. Patients were randomly assigned using a random number table: 48 received camrelizumab plus chemotherapy (control group), and 51 received camrelizumab plus apatinib (observation group). Clinical efficacy, serum tumor marker[carcinoembryonic antigen(CEA),carbohydrate antigen(CA)724,CA199,CA242]levels, immune function indicators(CD3+,CD4+,CD8+,CD4+/CD8+) levels before and after treatment, and adverse drug reaction (ADR) during treatment were compared between the 2 groups. RESULTS A total of 2 patients in the observation group and 3 in the control group were lost to follow-up. The disease control rate and objective response rate in the observation group were 95.92% and 85.71%, respectively, both significantly higher than 80.00% and 55.56% in the control group (P<0.05). The median progression-free survival was 9.61 months in the observation group, significantly longer than 6.72 months in the control group (P=0.011). Before treatment, there was no statistically significant difference in the levels of serum tumor markers and immune function indicators between the 2 groups (P>0.05). After treatment, the levels of CEA, CA724, CA199 and CA242 in 2 groups were significantly lower than before treatment, while the levels of CD3⁺, CD4⁺ and CD4 ⁺/CD8 ⁺ were significantly higher than before treatment, with greater improvements in the observation group (all P<0.05). The overall incidences of ADR and severe ADR showed no statistically significant difference between the 2 groups (P>0.05). CONCLUSIONS Camrelizumab combined with apatinib as first-line therapy for advanced gastric cancer may offer advantages over camrelizumab plus chemotherapy in terms of clinical efficacy and immune function improvement of patients, with an acceptable safety profile.
3.AI-HIP system for prosthesis size,global femoral offset and osteotomy in total hip arthroplasty
Guo-Yuan SUN ; Yan-Kun JIANG ; Tong LI ; Xue-Feng CONG ; Cheng HUANG ; Ran DING ; Wei-Guo WANG ; Qi-Dong ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(9):848-854
Objective To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty(THA)and its influence on clinical outcomes.Methods A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system(AI-HIP group),including 16 males and 20 females,aged from 43 to 81 years old with an average of(62.2±10.9)years old.According to the matching principle,36 patients who were planned by the traditional template method at the same period were selected as the control group,including 16 males and 20 females,aged from 40 to 80 years old with an average of(60.9±12.1)years old.The accuracy between two groups of prostheses were compared,as well as the combined eccentricity difference between preoperative planning and postoperative practice,lower limb length difference,osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect.Harris score and visual analogue scale(VAS)were used to evaluate clinical efficacy.Results Both groups were followed up for 12 to 18 months with an average of(14.5±2.1)months.The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2%,100%,58.3%,88.9%,respectively,which were better than 44.4%,83.3%,33.3%,66.7%in control group(P<0.05).There was no statistical significance in planning of femoral head prosthesis size(P>0.05).The actual combined eccentricity difference and combined eccentricity difference(practical-planning)in Al-HIP group were 1.0(0.2,2.4)mm and 1.1(-2.1,3.2)mm,respectively;which were better than 3.0(1.4,4.9)mm and 3.5(-1.6,6.5)mm in control group(P<0.05).There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter(P>0.05).In AI-HIP group,the actual difference of lower extremity length after surgery,the difference of lower extremity length(practical-planning),osteotomy height from the upper margin of lesser trochanter(practical-planning),actual topshoulder distance after surgery,and topshoulder distance(practical-planning)were 1.5(0.2,2.8),1.1(-0.3,2.2),2.1(-2.3,4.1),(15.3±4.1),2.2(-4.8,0.3)mm,respectively;which were better than control group of 2.6(1.3,4.1),2.5(0.3,3.8),5.8(-2.4,7.7),(13.0±4.3),-5.7(-9.4,-2.2)mm(P<0.05).At final follow-up,there were no significant differences in Harris scores of pain,function,deformity,total scores and VAS between two groups(P>0.05).The range of motion score was 4.8±0.6 in AI-HIP group,which was higher than that in control group(4.4±0.8)(P<0.05).Conclusion Compared with traditional template planning,AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk,restor-ing joint eccentricity,planning lower limb length,osteotomy height and top shoulder distance on the first unilateral THA,and the clinical follow-up effect is satisfactory.
4.Chemical constituents from Lonicera japonica and their antioxidant activities
Yuan LU ; Yan ZHANG ; Ying WANG ; Jia-Xuan DONG ; Bao-Yu DU ; Yong-Qing ZHANG ; Ran YANG
Chinese Traditional Patent Medicine 2024;46(8):2638-2644
AIM To study the chemical constituents from Lonicera japonica Thunb.and their antioxidant activities.METHODS The extract from L.japonica was isolated and purified by D101 macroporous resin,silica gel column and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH free radical scavenging method.RESULTS Fifteen compounds were isolated and identified as dearabinosyl pneumonanthoside(1),5α-carboxystrictosidine(2),apigenin 7-O-glucoside(3),ethyl caffeate(4),isorhamnetin-3-O-β-D-glucopyranoside(5),luteolin 7-O-glucoside(6),quercetin 3-O-β-glucoside(7),luteolin 7-O-rutinoside(8),luteolin-7-O-neohesperidoside(9),hydnocarpin(10),methyl chlorogenate(11),(Z)-aldosecolohanin(12),kaempferol 3-O-β-D-glucoside(13),chlorogenic acid butyl ester(14),(-)-syringaresinol(15).The IC50 values of DPPH free radical scavenging of compounds 3,5-10,13-14 were 6.70-36.25 μmol/L.CONCLUSION Compounds 1-2,8,9-11 and 15 are isolated from genus Lonicera for the first time.Compounds 3,5-10,13-14 show good antioxidant activities.
5.Comparison of the diagnostic efficacy between fine needle aspiration needles and end-cutting fine needle biopsy needles in endoscopic ultrasound-guided tissue acquisition for solid pancreatic lesions
Yundi PAN ; Chunhua ZHOU ; Minmin ZHANG ; Taojing RAN ; Xianzheng QIN ; Kui WANG ; Yao ZHANG ; Tingting GONG ; Ling ZHANG ; Dong WANG ; Xiangyi HE ; Wei WU ; Benyan ZHANG ; Lili GAO ; Duowu ZOU
Chinese Journal of Digestive Endoscopy 2024;41(11):864-870
Objective:To compare the diagnostic efficacy of 22 G fine needle aspiration (FNA) needles and 22 G end-cutting fine needle biopsy (FNB) needles for solid pancreatic lesion using both cytological and histological examination.Methods:Clinical data of 116 patients who underwent endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNA/FNB) at the Digestive Endoscopy Center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from June 2022 to March 2023 were retrospectively analyzed. Sixty-three patients sampled with 22 G FNA needles were the FNA group, and 53 sampled with 22 G FNB needles were the FNB group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and cytological and histological diagnostic yield of FNA needles and FNB needles for solid pancreatic lesions were compared.Results:There were no significant differences in age, gender, lesion location, lesion size, or the number of passes between the FNA group and the FNB group ( P>0.05). There were no significant differences in the diagnostic accuracy [93.7% (59/63) VS 90.6% (48/53), P=0.730], sensitivity [93.0% (53/57) VS 90.2% (46/51), P=0.732], specificity [100.0% (6/6) VS 100.0% (2/2), P=1.000], positive predictive value [100.0% (53/53) VS 100.0% (46/46), P=1.000] and negative predictive value [60.0% (6/10) VS 28.6% (2/7), P=0.335] of combined cytology and histology in distinguishing benign and malignant lesions between the two groups. In the FNA group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [93.7% (59/63) VS 81.0% (51/63), P=0.008], and was higher than histology alone without statistical significance [93.7% (59/63) VS 87.3% (55/63), P=0.125]. In the FNB group, the diagnostic accuracy of combined cytology and histology was higher than cytology alone [90.6% (48/53) VS 69.8% (37/53), P=0.001], but not than histology alone [90.6% (48/53) VS 90.6% (48/53), P=1.000]. For solid masses located in pancreatic body/tail, the diagnostic accuracy for malignancy by histology using FNB needles tended to be higher than that of FNA needles [100.0% (17/17) VS 81.3% (26/32), P=0.080]. Conclusion:Both FNA needles and FNB needles exhibit adequate diagnostic yield for solid pancreatic masses when combining cytology and histology. FNB needles may offer a higher histological diagnostic yield.
6.Treatment of uncontrolled motion faults of TiRobot surgery robot:Four case reports
Ran GAO ; Da-Wei GUO ; Zhen-Wei WANG ; Wei GUO ; Dong-Yan LIU
Chinese Medical Equipment Journal 2024;45(11):117-120
The composition and working principle of TiRobot surgery robot were introduced.Four cases of uncontrolled motion faults of the robot in image alignment of the main control trolley,precision of the navigation and positioning instruments,positional offset of the robotic arm and initialization of the optical tracking system were explored in terms of phenomenon,cause and treatment.References were provided for medical engineers to treat similar faults.[Chinese Medical Equipment Journal,2024,45(11):117-120]
7.Protective effect of racanisodamine on radiation-induced lung epithelial cell injury
Haochun GUO ; Jiajia CHEN ; Ran YU ; Hanxu YU ; Lei DONG ; Wanpeng WANG ; Haijun ZHANG
Chinese Journal of Radiation Oncology 2024;33(8):753-759
Objective:To investigate the protective effect of racanisodamine (654-2) on lung epithelial cell injury induced by X-ray in mice and unravel the underlying mechanism.Methods:Mouse alveolar epithelial cells MLE-12 were used to establish radiation-induced lung injury (RILI) model in vitro and divided into 4 groups as follows: control (no irradiation), radiation (16 Gy radiation), treatment 1 (16 Gy radiation + 2 μmol/L 654-2), treatment 2 (16 Gy radiation + 10 μmol/L 654-2), and inhibitor (16 Gy radiation + 10 μmol/L 654-2 + 2 μmol/L ML385), respectively. Cells were sampled at different time points after radiation. Cell senescence was detected with senescence-associated β-galactosidase (SA-β-Gal) staining. Cell colony-forming ability was detected to observe the recovery capability of cells after treatment. The expression levels of p21, p16, phosphorylated histone H2AX(γH2AX), nuclear factor erythroid-2 related factor 2 (Nrf2), Nrf2 Ser40 site phosphorylation (p-Nrf2), p62, heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1) proteins were measured by Western blot. Cell apoptosis and the production of intracellular reactive oxygen species (ROS) were determined by flow cytometry. The expression levels of glutathione (GSH) and superoxide dismutase (SOD) were detected according to the manufectuer instructions. The expression levels of glutamate-cysteine ligase catalytic subunit (GCLC) and glutamate-cysteine ligase modifier subunit (GCLM) mRNA were determined by real time reverse transcription PCR. Measurement data were expressed as Mean ±SD. Comparison between two groups was conducted by independent sample t-test, and comparison among multiple groups was performed by one-way ANOVA. Results:Compared with the radiation group, the proportion of cells with positive staining of SA-β-Gal was significantly lower and cell senescence were alleviated in the treatment 1 and 2 groups (all P<0.001). Compared with the radiation group, the expression level of γH2AX protein was significantly down-regulated ( P=0.037), cell apoptosis rate was significantly decreased ( P=0.026), the proliferation capacity of MLE-12 was enhanced ( P=0.004), GSH ( P=0.002) and SOD ( P<0.001) activity was enhanced and ROS production was declined ( P=0.001) in the treatment 2 group. The expression levels of Nrf2 and p-Nrf2 in total protein were up-regulated over the time of 654-2 intervention. Meanwhile, the expression levels of antioxidant proteins of NQO1 and HO-1 were up-regulated and that of GCLC and GCLM mRNA was also up-regulated. There were no significant differences in the number of cells with positive staining of SA-β-Gal ( P=0.145) and ROS production ( P=0.317) between the inhibitor and radiation groups after supplement of ML385, small-molecule inhibitor of Nrf2. Conclusion:654-2 can activate the Nrf2 pathway, enhance cell antioxidant capacity and inhibit cell senescence, thereby playing a protective role on radiation- induced lung injury.
8. Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy
Ying-Dong ZHOU ; Meng-Xian ZHANG ; Qing-Ling WANG ; Hao-Ran KANG ; Zhi-Cheng ZHANG ; Xiang-Dong GUO ; Qing-Lin WANG ; Ya-Min LIU
Chinese Pharmacological Bulletin 2024;40(3):455-461
Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by
9.Imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses and efficacy and safety of intravascular interventional therapy in them
Tengfei LI ; Qi TIAN ; Shuailong SHI ; Jie YANG ; Ye WANG ; Zhen CHEN ; Yuncai RAN ; Baohong WEN ; Dong GUO ; Shaofeng SHUI ; Xinwei HAN ; Xiao LI ; Ji MA
Chinese Journal of Neuromedicine 2024;23(1):42-47
Objective:To summarize the imaging features of severe unilateral transverse sinus and sigmoid sinus thromboses, and evaluate the efficacy and safety of intravascular interventional therapy in them.Methods:Thirty-seven patients with severe unilateral transverse sinus and sigmoid sinus thromboses clinically mainly manifested as intracranial hypertension and accepted endovascular intervention in Department of Interventional Radiology, First Affiliated Hospital of Zhengzhou University from June 2012 to September 2022 were chosen; their clinical data were retrospectively analyzed and imaging features were summarized. Short-term efficacy was evaluated according to blood flow restoration degrees and pressure gradient reduction in the occlusive sinus and modified neurological symptoms before and after endovascular intervention. Hospitalized complications were observed; safety and long-term efficacy were evaluated according to postoperative clinical follow-up and imaging results 6-12 months after endovascular intervention.Results:(1) Preoperative brain MRI and (or) CT showed different degrees of swelling of the brain tissues, with the affected side as the target; mixed signals/density shadow could be seen in the blocked transverse sinus and sigmoid sinus; venous cerebral infarction or post-infarction cerebral hemorrhage could be combined in some patients. MRV, CTV and DSA showed poor or completely occluded transverse sinus and sigmoid sinus while normal in the contralateral side; obvious thrombus filling-defect was observed in the occluded venous sinus after mechanical thrombolysis. (2) Occlusive sinus blood flow was restored in all patients after endovascular intervention, and pressure gradient of the occlusive segment decreased from (16.6±3.3) mmHg before to (2.8±0.8) mmHg after endovascular intervention. Before discharge, clinical symptoms of all patients were significantly improved (modified Rankin scale [mRS] scores of 0 in 30 patients, 1 in 5 patients, 2 in 1 patient and 3 in 1 patient), and 2 patients had unilateral limb movement disorder (muscle strength grading III and IV, respectively). All patients received clinical follow-up for (9.6±3.0) months. At the last follow-up, neurological function obviously improved compared with that before endovascular intervention, without new neurosystem-related symptoms (mRS scores of 0 in 30 patients, 1 in 6, and 2 in 1 patient). In 34 patients received MRV or DSA follow-up, 28 had complete recanalization of occlusive sinus and 6 had partial recanalization, without obvious stenosis or recurrent occlusion.Conclusions:Severe unilateral transverse sinus and sigmoid sinus thrombosis can cause local intracranial venous blood stasis, and then cause "increased regional venous sinus pressure", which is manifested as unilateral brain tissue swelling and even venous cerebral infarction or post-infarction cerebral hemorrhage. Early diagnosis and endovascular intervention can obviously improve the prognosis of these patients, enjoying good safety.
10.Protective effects of Ginkgo biloba extract on presbycusis in the rat model via autophagy pathway
Qing-Ling WANG ; Meng-Xian ZHANG ; Ying-Dong ZHOU ; Hao-Ran KANG ; Xiang-Dong GUO ; Qing-Lin WANG
Chinese Traditional Patent Medicine 2024;46(1):65-71
AIM To investigate the effects of Ginkgo biloba extract on hearing function,cochlear morphology and autophagy-related protein expression in a rat model of presbycusis.METHODS Forty-five rats were randomly divided into the control group,the model group and the low,medium and high dose G.biloba extract groups(10,20 and 30 mg/kg),with 9 rats in each group.The rat model of presbycusis was established by intraperitoneal injection of 500 mg/kg D-galactose(D-gal).Eight weeks after the corresponding administration,the rats had their changes of hearing threshold detected by the auditory brainstem evoked potential(ABR);their morphological changes of cochlear hair cells,stria vascularis(SV)and spiral ganglion cells observed by HE staining;their number of hair cells inside and outside the cochlea detected by immunofluorescence staining;their ultrastructure changes of cochlear hair cells observed by transmission electron microscopy;and their expression of autophagy-related proteins in cochlea tissue detected by Western blot.RESULTS Compared with the control group,the model group displayed increased ABR threshold(P<0.01);more severely damaged inner and outer hair cells,spiral ganglion cells and SV,decreased SV thickness and numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.01);decreased protein expressions of Beclin1 and LC3 Ⅱ and ratio of LC3 Ⅱ/LC3 Ⅰ in cochlear tissue(P<0.01),and higher P62 protein expression(P<0.01).Compared with the model group,the medium and high dose G.biloba extract groups shared decreased ABR thresholds(P<0.01);improved morphology of inner and outer hair cells and SV in the cochlea,normalized,morphology of spiral ganglion cells,and increased SV thickness and the numbers of spiral ganglion cells,inner and outer hair cells and autophagosomes(P<0.05,P<0.01);increased protein expressions of Beclin1 and LC3 Ⅱ and the ratio of LC3 Ⅱ/LC3 Ⅰ in the cochlea(P<0.01),and decreased P62 protein expression(P<0.01).CONCLUSION The protective effects G.biloba extract on hearing function and cochlear cells in the rat model of presbycusis may be associated with the up-regulated expression of Beclin1 and LC3 Ⅱ proteins and down-regulated P62 protein expression in cochlear tissues.

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