In recent years, growing evidence indicates that the nervous system plays an indispensable role in tumor development and metastasis. Elucidating crosstalk between the nervous system and tumor progression has thrived as a hot topic and a new direction for understanding cancer pathogenesis. Notably, many novel discoveries have suggested that neurotransmitter receptors (NRs) are not only widely expressed in cancer cells, but also play key roles in regulating cancer initiation and progression by diverse approaches. In this review, we summarized the latest advance in cancer neuroscience, especially emphasizing the important roles of different NRs in cancer development and prevention. The exemplary studies presented herein illustrate the emerging view that NRs are profoundly influential, manifested in tumor growth, apoptosis, angiogenesis, metastasis, resistance to drugs, and participate in the formation of neural-cancer interactions. In addition, NRs also regulate cellular metabolic processes and tumor microenvironment (TME) remodeling. More importantly, numerous basic and clinical studies have suggested that NRs may be potential targets for cancer treatments, and corresponding agonists or antagonists have been identified effectively in controlling tumor growth and metastasis. In conclusion, NRs are emerging as novel targets for anti-cancer drug exploration and clinical cancer treatments, while trying to uncover deeper mechanisms and connections between NRs and cancer is of high clinical significance and translational value.
Humans ; Neoplasms/metabolism* ; Receptors, Neurotransmitter/physiology* ; Animals ; Tumor Microenvironment/physiology*

OBJECTIVES: To explore the efficacy of DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy for management of cancer pain and provide reference for its standardized clinical application. Methods and. RESULTS: Recommendations were formulated based on literature review and expert group discussion, and consensus was reached following expert consultation. The consensus recommendations are comprehensive, covering the entire treatment procedures from preoperative assessment and preparation, surgical operation process, postoperative management and traditional Chinese medicine treatment to individualized treatment planning. The study results showed that the treatment plans combining traditional Chinese with Western medicine effectively alleviated cancer pain, reduced the use of opioid drugs, and significantly improved the quality of life and enhanced immune function of the patients. Postoperative follow-up suggested good treatment tolerance among the patients without serious complications. CONCLUSIONS The formulated consensus is comprehensive and can provide reference for clinicians to use DSA-guided intrathecal drug delivery system combined with Zi Wu Liu Zhu Acupoint Therapy. The combined treatment has a high clinical value with a good safety profile for management of cancer pain.
Humans ; Medicine, Chinese Traditional ; Cancer Pain/therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Drug Delivery Systems ; Pain Management/methods* ; China

BACKGROUND:Although traditional screw fixation has been successful in treating ankle fractures,rigid fixation solutions tend to restrict ankle movement and delay fracture healing,whereas elastic fixation is more compatible with human mechanics and has unique advantages in patients with ankle fractures. OBJECTIVE:To compare the clinical effectiveness of elastic fixation and absolute fixation in repairing ankle fractures in the elderly with lower tibiofibular instability. METHODS:The clinical data of 108 elderly ankle fractures with lower tibiofibular instability in Hengshui People's Hospital from August 2019 to August 2021 were retrospectively collected.They were divided into screw group and elastic fixation group(n=54 per group)according to the surgical protocol,and traditional screw internal fixation and elastic internal fixation were performed respectively.The perioperative indicators,surgical results,economic benefits,and American orthopedic foot and ankle society scores were collected and compared between the two groups.Serum tumor necrosis factor-α,interleukin-8 levels,ankle cavity width,depth,and lower tibiofibular space were compared before and after surgery. RESULTS AND CONCLUSION:(1)The full weight-bearing time was shorter in the elastic fixation group than that in the screw group;the operating angle was greater in the elastic fixation group than that in the screw group,and the complication rate was lower in the elastic fixation group than that in the screw group(P<0.05).(2)Serum tumor necrosis factor-α and interleukin-8 levels in the elastic fixation group were lower than those in the screw group 3 days after surgery(P<0.05).(3)American orthopedic foot and ankle society scores in the two groups were higher than those before surgery at 6 and 12 months after surgery,and the depth and width of the inferior tibiofibular space and ankle cavity were lower than those before surgery(P<0.05);but no significant difference was detected between the two groups(P>0.05).(4)There was no significant difference in the excellent and good rate between the two groups at 12 months after surgery(P>0.05).(5)There was no significant difference in the comparison of direct non-medical costs,direct medical costs,and total costs between the two groups(P>0.05).(6)It is indicated that elastic fixation for the repair of ankle fractures with lower tibiofibular instability in the elderly can obtain effective outcomes,which can shorten the time of complete weight-bearing,diminish complications,and alleviate inflammatory stress.

Objective:To evaluate the clinical value of intraoperative sliding CT in deep brain stimulation (DBS) for Parkinson's disease (PD).Methods:A total of 117 PD patients accepted DBS in Department of Neurosurgery, First Affiliated Hospital of Zhengzhou University from May 2019 to May 2023 were chosen; 46 patients had local anesthesia and 71 had general anesthesia. Bilateral subthalamic nucleus (STN) DBS was performed in 73 patients, bilateral medial globus pallidus (GPi) DBS was performed in 43 patients, and right GPi and left STN DBS was performed in 1 patient. Preoperative/intraoperative sliding CT images and preoperative MRI images were fused to calculate the spatial distance between the preoperative planned target and actual target (adjusting electrode position timely in case of spatial distance greater than 2 mm [electrode displacement]). Differences of spatial distance between preoperative planned target and actual target in patients accepted different types of anesthesia and surgical modalities were compared.Results:All 117 patients were successfully operated and 234 electrodes were implanted. No patients needed a second operation for misalignment of electrodes or poor efficacy. During CT scan, neither anesthesia extubation or mechanical collision nor intracranial hemorrhage complications occurred. Spatial distance between the preoperative planned target and actual target was (1.35±0.50) mm in 117 patients. Displacement was noted in 4 electrodes and immediately adjusted during the operation; and CT re-examination confirmed good electrode position. No statistical significance in spatial distance between the preoperative planned target and actual target was noted between the general anesthesia group and local anesthesia group, and between the STN group and GPi group ( P>0.05). Conclusion:Intraoperative sliding CT is simple, safe and effective, which helps to timely adjust the electrode position during operation, avoids second operation and complications, and improves the safety and efficacy of DBS.

Objective To analyze the interventional effect of high-flow nasal cannula oxygen (HFNC) therapy in patients with stable chronic obstructive pulmonary disease (COPD) combined with hypercapnia. Methods A total of 45 patients with stable COPD complicating with hypercapnia who require long-term oxygen therapy were selected as study subjects. They were divided into three groups based on different respiratory support modes: long-term home oxygen therapy (LTOT) group, non-invasive ventilation (NIV) group, and HFNC group, with 15 patients in each group. The general condition, blood gas index, lung function index, respiratory status, quality of life, and walking test results of the three groups were compared after discharge. Results During the follow-up period, the number of admission and acute exacerbation in the HFNC group and NIV group was lower than that in the LTOT group (P < 0.05). At 6 and 12 months after discharge, the arterial partial pressure of carbon dioxide [p_a(CO₂)] in the three groups was lower than before discharge, while the arterial partial pressure of oxygen[p_a(O₂)], pulse oxygen saturation (SpO₂), forced vital capacity (FVC), and forced expiratory volume in one second (FEV₁) were higher than before discharge. Moreover, the changes in the above indicators in the HFNC group were greater than those in the NIV group and LTOT group (P < 0.05). At 1-, 3-, 6-, and 12-month after discharge, the scores of dyspnea scale of the modified Medical Research Council (mMRC) and the St. George′s Respiratory Questionnaire (SGRQ) in the three groups gradually decreased, and the 6-minute walking distance (6MWD) gradually increased. Additionally, the changesin the above indicators in the HFNC group were greater than those in the NIV group and LTOT group (P < 0.05). Conclusion HFNC can effectively alleviate dyspnea symptoms, improve lung function, promote the recovery of blood gas indicators, enhance quality of life and exercise tolerance, and reduce re-hospitalization rates in patients with stable COPD combined with hypercapnia.

Objective:To investigate the safety and clinical effect of single-stage separation of 4-finger with contiguous gull wing flaps and preserving the dorsal metacarpal vein in Poland syndrome.Methods:From June 2013 to January 2018, 17 children with Poland syndrome were treated by contiguous gull wing flaps. Postoperative follow-up was conducted to observe the incidence of skin flap necrosis and finger vascular crisis. Morphology of the fingers web was evaluated by modified Withey score and Swanson hand function score. Paired t-test was used for intra group comparison. Results:The operation was successfully completed and there were no early complications such as vascular crisis and skin necrosis. All patients were followed up for 12-41 months, with an average of 23.1 months. All patients had a reconstruction depth of digital webbed at nearly 1/3 of the proximal phalanx. Both the appearance and function were satisfactory without conspicuous scar. The depth, width and slope of the webbed are normal without conspicuous scar. Withey score was 0-1, with an average score of 0.17. There was significant differences of Swanson hand function score between preoperative(16.3±1.4)% and postoperative(3.6±1.3)%( t=16.469, P<0.01). Conclusions:It is safe to treat the syndactyly deformity of Poland syndrome with single-stage separation of 4-finger with contiguous gull wing flaps and preserving the dorsal metacarpal vein. The clinical efficacy is reliable.

Objective:To investigate the safety and clinical effect of single-stage separation of 4-finger with contiguous gull wing flaps and preserving the dorsal metacarpal vein in Poland syndrome.Methods:From June 2013 to January 2018, 17 children with Poland syndrome were treated by contiguous gull wing flaps. Postoperative follow-up was conducted to observe the incidence of skin flap necrosis and finger vascular crisis. Morphology of the fingers web was evaluated by modified Withey score and Swanson hand function score. Paired t-test was used for intra group comparison. Results:The operation was successfully completed and there were no early complications such as vascular crisis and skin necrosis. All patients were followed up for 12-41 months, with an average of 23.1 months. All patients had a reconstruction depth of digital webbed at nearly 1/3 of the proximal phalanx. Both the appearance and function were satisfactory without conspicuous scar. The depth, width and slope of the webbed are normal without conspicuous scar. Withey score was 0-1, with an average score of 0.17. There was significant differences of Swanson hand function score between preoperative(16.3±1.4)% and postoperative(3.6±1.3)%( t=16.469, P<0.01). Conclusions:It is safe to treat the syndactyly deformity of Poland syndrome with single-stage separation of 4-finger with contiguous gull wing flaps and preserving the dorsal metacarpal vein. The clinical efficacy is reliable.

Objective:To explore the transcriptional regulation mechanism of transforming growth factor β 1 (TGF-β 1) on Meox1 and its effect on cell migration of adult human dermal fibroblasts (HDF-a). Methods:(1) HDF-a cells were cultured in RPMI 1640 complete medium (hereinafter referred to as routinely cultured). The cells were divided into TGF-β 1 stimulation group and blank control group. The cells in TGF-β 1 stimulation group were stimulated with 10 μL TGF-β 1 in the mass concentration of 1 mg/μL, while the cells in blank control group were stimulated with the equal volume of phosphate buffer solution. After 72 hours in culture, partial cells in both groups were collected for transcriptome sequencing. The genes with differential expression ratio greater than or equal to 2 and P<0.01 between the two groups were selected to perform enrichment analysis and analysis of metabolic pathways of the Kyoto Gene and Genome Encyclopedia with, and the expression value of Meox1 per million transcripts (TPM) was recorded ( n=3). Partial cells from the two groups were used to detect the Meox1 mRNA expression by real-time fluorescent quantitative reverse transcription polymerase chain reaction (RT-PCR) ( n=3). (2) Cultured HDF-a cells in the logarithmic growth phase (the same growth phase of cells below) were divided into empty plasmid group, Smad2 overexpression (OE) group, Smad3 OE group, and Smad4 OE group, which were transfected respectively with 2 μg empty pcDNA3.1 plasmid and pcDNA3.1 plasmids separately carrying Smad2, Smad3, and Smad4 for 6 hours, and then were routinely cultured for 48 hours. The Meox1 mRNA expression in the transfected cells of each group was detected by real-time fluorescent quantitative RT-PCR ( n=3). (3) HDF-a cells were routinely cultured and grouped the same as in experiment (1). After 72 hours in culture, the enrichment of Smad2, Smad3, and Smad4 protein on the Meox1 promoter in the cells of each group was detected by chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) ( n=3). (4) HDF-a cells were routinely cultured and divided into negative interference group, small interference RNA (siRNA)-Smad2 group, siRNA-Smad3 group, siRNA-Smad4 group, empty plasmid group, Smad2 OE group, Smad3 OE group, and Smad4 OE group, which were transfected respectively with 50 μmol/L random siRNA, siRNA-Smad2, siRNA-Smad3, siRNA-Smad4, 2 μg empty pcDNA3.1 plasmid and pcDNA3.1 plasmids separately carrying Smad2, Smad3, and Smad4 for 6 hours and then routinely cultured for 48 hours. The enrichment of Smad2, Smad3, and Smad4 protein on the Meox1 promoter in the cells of corresponding group was detected by ChIP-qPCR ( n=3). (5) Two batches of HDF-a cells were cultured and divided into negative interference group, siRNA-Meox1 group, empty plasmid group, and Meox1 OE group, which were transfected respectively with 50 μmol/L random siRNA, siRNA-Meox1, 2 μg empty pcDNA3.1 plasmid and pcDNA3.1 plasmid carrying Meox1 for 6 hours and then routinely cultured for 24 hours. One batch of cells were subjected to scratch test with the scratch width being observed 24 hours after scratching and compared with the initial width for scratch wound healing; the other batch of cells were subjected to Transwell assay, in which the migrated cells were counted after being routinely cultured for 24 hours ( n=3). (6) From January 2018 to June 2019, 3 hypertrophic scar patients (2 males and 1 female, aged 35-56 years) were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University) 8-12 months after burns. The scar tissue and normal skin tissue along the scar margin resected during surgery were taken, and immunohistochemical staining was performed to observe the distribution of Meox1 protein expression. Data were statistically analyzed with one-way analysis of variance and independent sample t test. Results:(1) After 72 hours in culture, a total of 843 genes were obviously differentially expressed between the two groups, being related to tissue repair, cell migration, inflammatory cell chemotaxis induction process and potential signaling pathways such as tumor necrosis factor, interleukin 17, extracellular matrix receptor. The TPM value of Meox1 in the cells of blank control group was 45.9±1.9, which was significantly lower than 163.1±29.5 of TGF-β 1 stimulation group ( t=6.88, P<0.01) with RNA-sequencing. After 72 hours in culture, the Meox1 mRNA expression levels in the cells of blank control group was 1.00±0.21, which was significantly lower than 11.00±3.61 of TGF-β 1 stimulation group ( t=4.79, P<0.01). (2) After 48 hours in culture, the Meox1 mRNA expression levels in the cells of Smad2 OE group, Smad3 OE group, and Smad4 OE group were 198.70±11.02, 35.47±4.30, 20.27±2.50, respectively, which were significantly higher than 1.03±0.19 of empty plasmid group ( t=31.07, 13.80, 13.12, P<0.01). (3) After 72 hours in culture, the enrichment of Smad2, Smad3, and Smad4 protein on the promoter of Meox1 in the cells of TGF-β 1 stimulation group was significantly higher than that of blank control group respectively ( t=12.99, 41.47, 29.10, P<0.01). (4) After 48 hours in culture, the enrichment of Smad2 protein on the promoter of Meox1 in the cells of negative interference group was (0.200 000±0.030 000)%, significantly higher than (0.000 770±0.000 013)% of siRNA-Smad2 group ( t=11.67, P<0.01); the enrichment of Smad2 protein on the promoter of Meox1 in the cells of empty plasmid group was (0.200 000±0.040 000)%, significantly lower than (0.700 000±0.090 000)% of Smad2 OE group ( t=8.85, P<0.01). The enrichment of Smad3 protein on the promoter of Meox1 in the cells of negative interference group was (0.500 0±0.041 3)%, significantly higher than (0.006 0±0.001 3)% of siRNA-Smad3 group ( t=17.79, P<0.01); the enrichment of Smad3 protein on the promoter of Meox1 in the cells of empty plasmid group was (0.470 0±0.080 0)%, which was significantly lower than (1.100 0±0.070 0)% of Smad3 OE group ( t=9.93, P<0.01). The enrichment of Smad4 protein on the promoter of Meox1 in the cells of negative interference group was similar to that of siRNA-Smad4 group ( t=2.11, P>0.05); the enrichment of Smad4 protein on the promoter of Meox1 in the cells of empty plasmid group was similar to that of Smad4 OE group ( t=0.60, P>0.05). (5) Twenty-four hours after scratching, the scratch healing width of cells in siRNA-Meox1 group was narrower than that of negative interference group, while that of Meox1 OE group was wider than that of empty plasmid group. After 24 hours in culture, the number of migration cells in negative interference group was significantly higher than that in siRNA-Meox1 group ( t=9.12, P<0.01), and that in empty plasmid group was significantly lower than that in Meox1 OE group ( t=8.99, P<0.01). (6) The expression of Meox1 protein in the scar tissue was significantly higher than that in normal skin of patients with hypertrophic scars. Conclusions:TGF-β 1 transcriptionally regulates Meox1 expression via Smad2/3 in HDF-a cells, thus promoting cell migration.

Objective To evaluate the relationship between different levels of central venous pres-sure (CVP) and blood loss during pediatric living donor liver transplantation (LDLT). Methods Pediat-ric patients underwent LDLT in Renji Hospital from 2006 to August 10, 2016 were retrospectively reviewed. The patients were divided into 2 groups according to the different CVP levels before peritoneum closure:central venous pressure<10 mmHg group ( group L) and CVP≥10 mmHg group ( group H) . The primary outcome measure was intraoperative blood loss. The secondary outcome measures were duration of mechani-cal ventilation in intensive care unit (ICU), duration of ICU stay, length of postoperative hospital stay, intraoperative blood loss, intraoperative blood transfusion, intraoperative volume of liquid infused, opera-tion time and anesthesia time. Results A total of 442 pediatric patients were enrolled in this study, with 209 cases in group L and 233 cases in group H. Compared with group H, the intraoperative blood loss was significantly decreased, the anesthesia time, operation time and length of postoperative hospital stay were shortened ( P<0. 05) , and no significant change was found in intraoperative blood transfusion, intraopera-tive volume of liquid infused, duration of mechanical ventilation in ICU or duration of ICU stay in group L ( P>0. 05) . Conclusion Maintaining intraoperative CVP<10 mmHg can markedly reduce the blood loss during LDLT and is helpful for postoperative recovery in pediatric patients.

Objective: To evaluate the outcome of long-term cognitive function after liver transplantation in children and the role of age factor. Methods: Ninety-five pediatric patients, aged 2 yr and 6 months to 6 yr and 11 months at test, at least 1 yr after liver transplantation, were selected.The children′s cognitive function was assessed using Chinese Wechsler Intelligence Scale for Children.The patients were divided into 2 groups according to the age at transplantation: ≤1 yr group (L1 group, n=65) and > 1 yr group (M1 group, n=22). Results: Compared with the normal value, the scores of verbal comprehension and total intelligence quotient (IQ) were significantly decreased, and the proportion of children who had above-average IQ was decreased 1 yr after liver transplantation, the scores of verbal comprehension were decreased, and the proportion of children who had above-average IQ was decreased in group L1, and the scores of verbal comprehension, visual space and total IQ were significantly decreased, the proportion of children who had above-average IQ was reduced, and the proportion of children who had below-average IQ was increased in group M1(P<0.05). Compared with L1 group, the total IQ score was significantly decreased, the proportion of children who had above-average IQ was reduced, and the proportion of children who had below-average IQ was increased in group M1 (P<0.05). Conclusion The long-term cognitive function of children after liver transplantation is lower than that of normal children, and the long-term cognitive function of children ≤1 yr is better than that of children >1 yr.