ObjectiveAs a second messenger in intracellular signal transduction, Ca²⁺ plays an important role in cell migration. Previous studies have demonstrated that extracellular Ca²⁺ influx can promote electric field-guided cell migration, known as electrotaxis. However, the effect of intracellular Ca²⁺ flow on electrotaxis is unclear. Therefore, in this study, we investigate the effect of Ca²⁺ flux on the electrotaxis of Dictyostelium discoideum. MethodsThe electrotaxis of Dictyostelium discoideum was investigated by applying a direct current (DC) electric field. Cell migration was recorded using a real-time imaging system. Calcium channel inhibitors, the extracellular Ca²⁺ chelator EGTA, Ca²⁺-free DB buffer, and caffeine were applied to investigate the impact of intra- and extracellular Ca²⁺ flow on electrotaxis. The involvement of G proteins and ERK2 in directed cell migration mediated by endoplasmic reticulum Ca²⁺ release was explored using mutants. ResultsDictyostelium discoideum migrated toward the cathode in the electric field in a voltage-dependent manner. The intracellular Ca²⁺ concentration of the cells was significantly increased in the electric field. Inhibition of both extracellular Ca²⁺ influx and intracellular Ca²⁺ release suppressed cell electrotaxis migration. Inhibition of endoplasmic reticulum Ca²⁺ release induced by caffeine significantly impaired the electrotaxis of Dictyostelium discoideum. Deletion of Gα2, Gβ, Gγ, and Erk2 notably reduced the electrotaxis of the cells. Enhancing Ca²⁺ release mediated by caffeine restored the electrotaxis of the Gα2^-, Gβ ^-, and Erk2^- mutant cells partially or completely, but did not restore electrotaxis in the Gγ^- mutant cells. ConclusionCa²⁺ release from the endoplasmic reticulum regulates electrotaxis migration in Dictyostelium discoideum and is involved in the regulation of cell electrotaxis by G proteins and ERK2.

ObjectiveTo explore the pathological mechanism-syndrome-treatment patterns of approved Chinese patent medicines （CPMs） that treat collateral disorders， providing a reference for the principle of "treating different diseases with the same therapy" in collateral pathology. MethodsCPMs that apply treatment strategies based on collateral disorders were identified from the Pharmacodia database by extracting information from the "efficacy" or "indications" sections of drug package inserts. A database was established to extract the names and compositions of the CPMs， as well as their indications， related traditional Chinese medicine （TCM） symptoms， disease locations （affected areas）， and pathological factors. Frequency statistics were performed. Using the Apriori algorithm， an association rule analysis was conducted on CPMs and disease-location combinations related to the top three most frequent pathological factor combinations. Core formulas for these combinations were identified and analyzed through drug network analysis and MCODE module clustering. ResultsA total of 660 CPMs targeting collateral disorders were retrieved， involving 299 indications， 323 TCM symptoms， 21 disease locations， 19 pathological factors， and 124 pathological factor combinations. The most frequent pathological factor combinations were blood stasis （involved in 109 CPMs， 16.52%）， exogenous wind （外风） -cold-dampness （involved in 43 CPMs， 6.52%）， and qi deficiency-blood stasis （involved in 42 CPMs， 6.36%）. Analysis of the core formulas for these combinations revealed common ingredients such as Honghua （Carthami Flos）， Chuanxiong （Chuanxiong Rhizoma）， Danggui （Angelicae Sinensis Radix）， and Dilong （Pheretima）. ConclusionCollateral disorders involve a wide range of pathogenesis and represent a fundamental mechanism in the onset and development of various diseases， characterized by obstruction and stagnation. The primary therapeutic principle is unblocking of the collaterals. Blood stasis obstructing the collaterals is the core pathological basis， and the strategy of activating blood circulation and resolving stasis to unblock the collaterals should be central to the treatment. The core medication pattern involves combining blood-activating and stasis-resolving herbs with insect-derived medicinals that unblock collaterals. Exogenous wind is often the initiating patholo-gical factor in colla-teral disorders， and the appropriate addition of wind-dispelling herbs can enrich the treatment strategies for such conditions.

As a microbial therapy method, fecal microbiota transplantation (FMT) has attracted the attention of researchers in recent years. As one of the most direct and effective methods to improve gut microbiota, FMT achieves therapeutic benefits by transplanting functional gut microbiota from healthy human feces into the intestines of patients to reconstruct new gut microbiota. FMT has been proven to be an effective treatment for gastrointestinal diseases such as Clostridium difficile infection, irritable bowel syndrome, and inflammatory bowel disease. In addition, the clinical and basic research of FMT outside the gastrointestinal system is also emerging. It is worth noting that there is bidirectional communication between the gut microbial community and the central nervous system (CNS) through the gut-brain axis. Some gut bacteria can synthesize and release neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA) and dopamine. Imbalanced gut microbiota may interfere with the normal levels of these neurotransmitters, thereby affecting brain function. Gut microbiota can also produce metabolites that may cross the blood-brain barrier and affect CNS function. FMT may affect the occurrence and development of CNS and its related diseases by reshaping the gut microbiota of patients through a variety of pathways such as nerves, immunity, and metabolites. This article introduces the development of FMT and the research status of FMT in China, and reviews the basic and clinical research of FMT in neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), neurotraumatic diseases (spinal cord injury, traumatic brain injury) and stroke from the characteristics of three types of nervous system diseases, the characteristics of intestinal flora, and the therapeutic effect and mechanism of fecal microbiota transplantation, summarize the common mechanism of fecal microbiota transplantation in the treatment of CNS diseases and the therapeutic targets. We found that the common mechanisms of FMT in the treatment of nervous system diseases may include the following 3 categories through summary and analysis. (1) Gut microbiota metabolites, such as SCFAs, TMAO and LPS. (2) Inflammatory factors and immune inflammatory pathways such as TLR-MyD88 and NF-κB. (3) Neurotransmitter 5-HT. In the process of reviewing the studies, we found the following problems. (1) In basic researches on the relationship between FMT and CNS diseases, there are relatively few studies involving the autonomic nervous system pathway. (2) Clinical trial studies have shown that FMT improves the severity of patients’ symptoms and may be a promising treatment for a variety of neurological diseases. (3) The improvement of clinical efficacy is closely related to the choice of donor, especially emphasizing that FMT from healthy and young donors may be the key to the improvement of neurological diseases. However, there are common challenges in current research on FMT, such as the scientific and rigorous design of FMT clinical trials, including whether antibiotics are used before transplantation or different antibiotics are used, as well as different FMT processes, different donors, different functional analysis methods of gut microbiota, and the duration of FMT effect. Besides, the safety of FMT should be better elucidated, especially weighing the relationship between the therapeutic benefits and potential risks of FMT carefully. It is worth mentioning that the clinical development of FMT even exceeds its basic research. Science and TIME rated FMT as one of the top 10 breakthroughs in the field of biomedicine in 2013. FMT therapy has great potential in the treatment of nervous system diseases, is expected to open up a new situation in the medical field, and may become an innovative weapon in the medical field.

Objective To compare the fidelity of chronic obstructive pulmonary disease(COPD)models established using two methods:exposure to cigarette smoke(CS)and exposure to motor vehicle exhaust(MVE)in rats.Methods Twenty-four male SD rats were randomly divided into control,CS-exposed(CS),and MVE-exposed(MVE)groups,with 8 rats per group.Rats in CS and MVE groups were exposed to CS or MVE,respectively,to induce COPD models.After COPD model established,lung function of each group was assessed.Bronchoalveolar lavage fluid(BALF)was collected to measure inflammatory cell counts,levels of inflammatory cytokines interleukin-6(IL-6)and tumor necrosis factor(TNF)-α,and expression levels of mucin 5AC(MUC5AC).Lung tissue sections were stained with hematoxylin and eosin(HE)to observe pulmonary tissue and airway pathological changes.Periodic acid-Schiff(PAS)staining was used to detect goblet cell hyperplasia in airways.Results Compared with control group,rats in CS and MVE groups showed significantly increased inspiratory resistance(RI),total lung capacity(TLC),and lung static compliance(Cchord)(P<0.05),while expiratory flow parameters FEV50/FVC were significantly decreased(P<0.05).Compared with MVE group,rats in CS group had significantly higher RI,TLC,and Cchord(P<0.05),and lower FEV50/FVC(P<0.05).HE staining of lung tissues showed that mean linear intercept(MLI)was significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having higher MLI than MVE group(P<0.05).BALF analysis revealed that white blood cells,neutrophils,macrophages,lymphocytes,IL-6,and TNF-α levels were significantly higher in both CS and MVE groups compared with control group(P<0.05),and inflammatory cell counts,IL-6,and TNF-α levels were higher in CS group compared with MVE group(P<0.05).PAS staining of lung tissues indicated that goblet cells in large airways were significantly increased in both CS and MVE groups compared with control group(P<0.05),with CS group showing higher goblet cell counts than MVE group(P<0.05).Expression levels of MUC5AC in BALF were significantly higher in both CS and MVE groups compared with control group(P<0.05),with CS group having significantly higher MUC5AC levels than MVE group(P<0.05).Conclusions Exposure to CS or MVE can establish a rat model of COPD,with CS exposure better mimicking characteristics of acute exacerbation of COPD compared to MVE exposure.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective: There is controversy among different guidelines regarding the use of thermal ablation to treat clinical T1a renal cell carcinomas with tumor sizes ranging from 3.1–4 cm. Therefore, we compared oncological outcomes between heat-based thermal ablation (hTA) and cryoablation (CA) in patients with solid T1a renal cell carcinomas, including those with a tumor size ≤3 cm and a tumor size of 3.1–4 cm. Materials and Methods: Within the Surveillance, Epidemiology, and End Results database (2000–2019), we identified patients with clinical T1a renal cell carcinomas that were histologically confirmed and treated with hTA or CA. After propensity score matching using a 1:1 ratio, the overall survival (OS) and cancer-specific survival (CSS) were estimated and compared between the two methods. Cancer-specific mortality (CSM) was also analyzed, considering other-cause mortality as a competing risk. Results: Of the 3513 assessable patients, 1426 (40.6%) and 2087 (59.4%) were treated with hTA and CA, respectively. After propensity score matching, the hTA and CA groups included 1393 and 1393 patients, respectively. hTA was associated with shorter OS than CA with a hazard ratio of 1.17 (95% confidence interval, 1.04–1.32; P = 0.010). The hTA and CA groups did not reveal statistically significant differences in CSS with a hazard ratio of 1.07 (95% confidence interval, 0.76–1.50; P = 0.706). The hTA and CA groups did not show statistically significant differences in CSM (P = 0.849). However, the hTA group showed a significantly higher other-cause mortality (P = 0.011). Conclusion In patients with clinical stage T1a renal cell carcinomas, hTA was comparable to CA in terms of CSS and CSM.However, hTA resulted in a slightly shorter OS than CA. Large-scale randomized clinical trials are required to obtain more robust evidence.

Objective To analyze the relationship between diurnal temperature range (DTR) and the hospitalization of stroke in Lanzhou,so as to provide a scientific basis for probing into the mechanism of temperature changes in inducing stroke and formulating comprehensive prevention and control measures for stroke by relevant departments.Methods The information of the patients hospitalized due to stroke in Lanzhou during January 2014 to December 2019 and the air pollutants (PM₁₀,SO₂,and NO₂) and meteorological data in the same period were collected for statistical analysis.Spearman rank correlation analysis was performed to analyze the correlations between air pollutants and meteorological factors.The distributed lag nonlinear model was adopted to fit the relationship between DTR and the number of stroke inpatients,and three-dimensional diagrams and the correlation diagrams of DTR against stroke risk were established.The stratified analysis was performed according to gender and age (< 65 years and ≥65 years).Results From 2014 to 2019,a total of 92 812 stroke patients were hospitalized in Lanzhou,with a male-to-female ratio of 1.35:1.There was a nonlinear relationship between DTR and the number of stroke inpatients in Lanzhou,which presented a lag effect.The low DTR at 4.5 ℃ had the largest RR value of 1.25 (95%CI=1.16-1.35) for stroke inpatients at a cumulative lag of 18 d.The effect of high DTR (18.5 ℃) on the hospitalization of stroke patients peaked at a cumulative lag of 21 d,with an RR value of 1.09 (95%CI=1.01-1.18).The stratified analysis results suggested that low levels of DTR had greater effects on the hospitalization of male stroke patients and stroke patients <65 years.Conclusions Short-term exposure to different levels of DTR had an impact on the number of stroke inpatients,and low levels of DTR had a slightly greater impact on stroke inpatients than high levels of DTR.Importance should be attached to the protection of males and people aged <65 years at low levels of DTR.
Humans ; Male ; Female ; Temperature ; Stroke ; Cold Temperature ; Hot Temperature ; Air Pollutants ; China/epidemiology*