Objective The athletic performance and physiological indicators of two top seated cross-country skiers during simulated competitions were analyzed,and the characteristics of exercise intensity and pacing strategies in different terrains were explored,so as to provide a scientific basis for physical fitness allocation and speed rhythm optimization of the athletes.Methods Differential global positioning system and Momentum Technology MT-Sports T2 were used to test athlete A and athlete B with class of locomotor winter 10(LW 10),who were the first and second runners-up of Beijing Winter Paralympic mid-distance cross-country ski race.The athletes' real-time gliding speed and heart rate during five consecutive 15 km cross-country skiing time trials were collected,and the time spent on each section,speed and heart rate changes in each course were analyzed.Results The coefficient of variation(CV)of mean heart rate on uphill and flat terrain sections were significantly correlated with total scores.The average gliding speed and average heart rate as a percentage of maximum heart rate(HRmax)of the athletes in three terrains were significantly correlated with total scores.The correlation between the mean time spent on uphill and flat terrain and total performance was stronger than that between the mean time spent on downhill terrain and total scores.Both athletes used a cumulative acceleration speed rhythm.Conclusions Uphill and flat terrain time are critical to race performance.Athletes adopt a progressive pacing strategy,gradually increasing speed in the first half,maintaining stable output in the mid-race,and finishing the last lap at a high-speed.Heart rates are mainly distributed between 70％-90％HRmax,and balancing high-intensity efforts on uphills with recovery on downhills helps optimize energy expenditure.

Objective The athletic performance and physiological indicators of two top seated cross-country skiers during simulated competitions were analyzed,and the characteristics of exercise intensity and pacing strategies in different terrains were explored,so as to provide a scientific basis for physical fitness allocation and speed rhythm optimization of the athletes.Methods Differential global positioning system and Momentum Technology MT-Sports T2 were used to test athlete A and athlete B with class of locomotor winter 10(LW 10),who were the first and second runners-up of Beijing Winter Paralympic mid-distance cross-country ski race.The athletes' real-time gliding speed and heart rate during five consecutive 15 km cross-country skiing time trials were collected,and the time spent on each section,speed and heart rate changes in each course were analyzed.Results The coefficient of variation(CV)of mean heart rate on uphill and flat terrain sections were significantly correlated with total scores.The average gliding speed and average heart rate as a percentage of maximum heart rate(HRmax)of the athletes in three terrains were significantly correlated with total scores.The correlation between the mean time spent on uphill and flat terrain and total performance was stronger than that between the mean time spent on downhill terrain and total scores.Both athletes used a cumulative acceleration speed rhythm.Conclusions Uphill and flat terrain time are critical to race performance.Athletes adopt a progressive pacing strategy,gradually increasing speed in the first half,maintaining stable output in the mid-race,and finishing the last lap at a high-speed.Heart rates are mainly distributed between 70％-90％HRmax,and balancing high-intensity efforts on uphills with recovery on downhills helps optimize energy expenditure.

Objective:To evaluate the effect of selective cerebral mild hypothermia on the expression of histone deacetylase 1-3 (HDAC1-3) during focal cerebral ischemia-reperfusion (I/R) in rats.Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 240-260 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (S group), focal cerebral I/R group (I/R group), selective cerebral mild hypothermia group (SCH group), and normothermia group (N group). Only the cervical vessels were isolated in S group. In the other three groups, sutures were inserted into the internal carotid artery to block the middle cerebral artery for 2 h, and then the sutures were pulled out to restore perfusion for 24 h. A focal cerebral I/R model was prepared. Normal saline at 20 ℃ and 37 ℃ was infused into the internal carotid artery at a rate of 0.6 ml/min for 10 min starting from the time point immediately after removal of the sutures in SCH group and N group respectively. Cerebral temperature and rectal temperature were continuously monitored during the operation. The modified neurological severity score (mNSS) was assessed at 24 h of reperfusion. The rats were then sacrificed under deep anesthesia and brains were obtained for determination of cerebral infarct size (by TTC staining). The tissues of the cerebral ischemic penumbra were taken for determination of the apoptosis rate of neurons (by TUNEL method) and lactylation modification and expression of HDAC1-3 (by Western blot) and for observation of the morphology of neurons (by HE staining). Results:Compared with S group, the mNSS, cerebral infarct size and apoptosis rate of neurons were significantly increased, HDAC1-3 expression was down-regulated, and the lactylation modification was increased in the other three groups ( P<0.05). Compared with I/R and N groups, the mNSS, cerebral infarct size and apoptosis rate of neurons were significantly decreased, HDAC1-3 expression was up-regulated, and the lactylation modification was decreased in SCH group ( P<0.05). There was no statistically significant difference in the aforementioned parameters between I/R group and N group ( P>0.05). HE staining showed that the morphology of neurons was intact and well-defined in S group, a large number of cells with edema and irregularly solidified nuclei were found in I/R group and N group, and the nuclear shrinkage and morphological changes of neurons were alleviated in SCH group. Conclusions:The mechanism by which selective cerebral mild hypothermia alleviates cerebral I/R injury may be related to up-regulation of HDAC1-3 expression in rats.

Kunxian Capsule (KX) is a popular Chinese patent medicine for the treatment of rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus, Henoch-Schönlein purpura, ankylosing spondylitis, psoriatic arthritis and eczema. However, there is scarcity of comprehensive information on the significance of KX in the clinical application and its side effects. Hence, it is aimed to provide a review of the significance of KX, with a focus on the pharmacological effects, clinical applications, and its adverse reactions. This review was based on the published literatures in PubMed, China National Knowledge Infrastructure and WanFang database. The articles were collected by two independent authors with no time limits applied until November 30, 2022. The search term includes Kunxian Capsule and/or clinical effect, pharmacology, disease, therapy, adverse effects and quality control. KX has been shown to be effective in the treatment of autoimmune arthritis by inhibiting inflammatory responses and inducing apoptosis. Many studies suggest that KX has anti-inflammatory and analgesic properties that aid in the improvement of joint functions. KX dispels wind, removes dampness, invigorates the kidneys, and promotes blood circulation, thereby curing various diseases. However, studies also suggest KX-related adverse reactions in multiple systems. Overall, this review highlights the scientific basis of KX in curing or preventing various diseases and provides novel insights for further research and clinical applications.

Objective:To evaluate the effect of selective cerebral mild hypothermia on small ubiquitin-like modifier 2/3 (SUMO2/3) modification of dynamin-related protein 1 (Drp1) in a rat model of cerebral ischemia-reperfusion (I/R).Methods:Sixty clean-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 240-260 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (S group), cerebral I/R group (I/R group), selective cerebral mild hypothermia group (HT group) and normal temperature group (NT group). The operation was performed under the monitoring of cerebral temperature and rectal temperature.Only the cervical blood vessels were exposed in S group, while focal cerebral I/R was induced by 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in anesthetized animals in the other three groups.In HT group and NT group, 4 and 37 ℃ normal saline was perfused through the left internal carotid artery at a rate of 80 ml·kg -1·h -1 for 15 min, respectively. Modified neurological severity score (mNSS) was assessed at 24 h of reperfusion. Then the rats were sacrificed under deep anesthesia, brains were removed, brain tissues were obtained for determination of the percentage of cerebral infarct size (by TTC staining), and the ischemic penumbra tissues in the cerebral cortex were removed for examination of the ultra-structural changes of mitochondria (with a transmission electron microscope) and for determination of the SUMO2/3 modification of Drp1 (by CO-IP), expression of total Drp1 (T-Drp1) and total cytochrome c (T-Cytc) (by Western blot), and expression of mitochondrial outer membrane Drp1 (M-Drp1) and cytoplasmic Cytc (C-Cytc) (by Western blot) after isolation of mitochondria and cytoplasm. Results:Compared with S group, the mNSS and percentage of cerebral infarct size were significantly increased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was up-regulated, and SUMO2/3 modification of Drp1 in ischemic penumbra area was increased ( P<0.05), the fragmentation of mitochondria was aggravated, and cristae rupture and vacuolation were obvious in the other three groups. Compared with I/R group, the mNSS and percentage of cerebral infarct size were significantly decreased, the expression of M-Drp1, T-Drp1, C-Cytc and T-Cytc was down-regulated, SUMO2/3 modification of Drp1 was increased ( P<0.05), the fragmentation of mitochondria was significantly attenuated, and cristae rupture and vacuolation were weakened in HT group. There were no significant differences in these detection parameters between NT group and I/R group ( P>0.05). Conclusions:The mechanism by which selective cerebral mild hypothermia alleviates the cerebral I/R injury is related to increased SUMO2/3 modification of Drp1, decreased binding of Drp1 to mitochondrial outer membrane, and reduced mitochondrial excessive fission in rats.

[摘 要] 目的：采用基于中国人群单核苷酸多态性位点开发的同源重组缺陷（HRD）检测工具评估云南地区卵巢癌患者的HRD状态和BRCA1/2基因突变频率并探讨其临床意义。方法：共纳入2021年1月至2023年5月间在云南省肿瘤医院收治的卵巢癌患者248例，HRD状态采用基因组瘢痕评分法（GSS）（主要依据拷贝数的长度、类型、位置及基因组断片）或HRD评分法（杂合性缺失、端粒等位基因失衡及大片段移位等基因组不稳定事件的总和）进行评估，当组织样本的GSS≥50分或HRD评分≥42分者或检测到有害的BRCA1/2基因突变时HRD被定义为阳性。分析患者HRD状态与临床病理特征的关系。结果：248名卵巢癌患者中70.97%的患者HRD呈阳性，其中BRCA1/2基因突变率为30.65%。Ⅲ~Ⅵ期、高级别浆液腺癌的卵巢癌患者具有更高的HRD阳性率（均P<0.01），HRD评分更高的患者其合并其他基因突变的频率也越高（P<0.05）。HRD状态与卵巢癌的病理类型、临床分期和其他基因突变均有关联（均P<0.01）。结论：云南地区卵巢癌患者HRD阳性率较高，HRD阳性的卵巢癌患者可以从聚ADP核糖聚合酶（PARP）抑制剂治疗中获得更大的收益。

Shengmai Yin (SMY) is a Chinese herbal decoction that effectively alleviates the side effects of radio-therapy in various cancers and helps achieve radiotherapy's clinical efficacy.In this study,we explored the interaction mechanism among SMY,DNA methylation,and nasopharyngeal carcinoma (NPC).We identified differences in DNA methylation levels in NPC CNE-2 cells and its radioresistant cells (CNE-2R)using the methylated DNA immunoprecipitation array and found that CNE-2R cells showed genome-wide changes in methylation status towards a state of hypomethylation.SMY may restore its original DNA methylation status,and thus,enhance radiosensitivity.Furthermore,we confirmed that the dif-ferential gene Tenascin-C (TNC) was overexpressed in CNE-2R cells and that SMY downregulated TNC expression.This downregulation of TNC inhibited NPC cell radiation resistance,migration,and invasion.Furthermore,we found that TNC was hypomethylated in CNE-2R cells and partially restored to a hypermethylated state after SMY intervention.DNA methyltransferases 3a may be the key protein in DNA methylation of TNC.

Objective:To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment.Methods:Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital.Results:The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men ( P<0.001) and displayed a downward trend with age ( P=0.03). The mutation rate of ethnic minorities was higher than Han ( P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history ( P<0.001), and patients without drinking history was higher than patients with drinking history ( P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history ( P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types ( P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients ( P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples ( P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area ( P<0.001). Multivariate analysis showed that gender ( P<0.001), age ( P=0.036), smoking history ( P<0.001), pathological type ( P<0.001), specimen type ( P<0.001), and whether or not Xuanwei area ( P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area ( P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han ( P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities ( P=0.005). Conclusions:The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.

Objective:To analyze the expressions of non-small-cell lung cancer (NSCLC) driver genes and their mutation distribution characteristics in the Yunnan-Kweichow plateau, and to provide evidences for personalized molecular targeted therapy of lung cancer in high-incidence areas.Methods:A retrospective analysis was performed on the medical records of patients with NSCLC who underwent combined lung cancer 8 gene detection, including epidermal growth factor receptor (EGFR), rat sarcoma viral oncogene (RAS), anaplastic lymphoma kinase (ALK), RET proto-oncogene (RET), v-Raf murine sarcoma viral oncogene homolog (BRAF), ROS proto-oncogene 1 (ROS1), human epidermal growth factor receptor-2 (HER-2), and cellular-mesenchymal to epithelial transition factor (MET), from January 2016 to August 2019 in Yunnan Cancer Hospital. Besides, we analyzed the expressions of NSCLC driver genes and their mutation distributions.Results:The positive rate of NSCLC driver genes in Yunnan was 67.05%(1 508/2 249). The mutation rates in Xishuangbanna (76.92%), Yuxi (72.38%), Xuanwei (71.88%), Qujing (71.24%), and Honghe (71.79%) were significantly higher than other areas. The mutation rates of Hui (84.38%), Hani (85.00%), Zhuang (75.00%), Buyi (100%), Manchu (100%), Tujia (100%) and Achang (100%) are significantly higher than the minority national average. Driver gene mutations were related to gender ( P<0.001), smoking history ( P<0.001), age ( P<0.001), pathological type ( P<0.001), and whether the Xuanwei area ( P=0.027), but not related to the nationality ( P=0.748) and family history of lung cancer ( P=0.676). The mutation rates of EGFR, RAS, BRAF, HER-2 and MET genes were 44.46%, 10.98%, 1.24%, 0.89% and 0.76%, and the rearrangement rates of ALK, RET and ROS1 genes were 4.67%, 1.29% and 0.89%, respectively.The mutation rate of EGFR in females was 56.67%, which was higher than 33.19% in males ( P<0.001). The mutation rate of RAS in males was 12.66%, which was higher than 9.17% in females ( P=0.010). The mutation rate of RAS in the Han was 11.49%, which was higher than 7.17% in the minority ( P=0.032). The rate of RAS mutation in Xuanwei patients was 24.74%, significantly higher than 8.15% in non-Xuanwei area ( P<0.001), and the EGFR mutation rate was 40.63%, which was lower than 45.25% in non-Xuanwei area ( P=0.045). The rate of ALK rearrangement in Xuanwei patients was 1.56%, which was significantly lower than 5.31% in the non-Xuanwei area ( P<0.001), and no HER-2 mutation patients were detected in Xuanwei area. The mutation rate of EGFR in patients with non-smoking history was 51.10%, significantly higher than 29.70% of patients with smoking history ( P<0.001). Meanwhile, the rate of ALK rearrangement with non-smoking history patients was 5.35%, which was also higher than 3.16% of patients with smoking history ( P<0.001). The rate of RAS mutation in patients with non-smoking history was 9.34%, lower than 14.63% of patients with smoking history ( P=0.008). Conclusions:The positive rate of driven gene expression in NSCLC patients from the Yunnan-Kweichow Plateau is slightly lower than the national average. The rates of EGFR and RAS mutations are similar to the domestic average. The rates of ROS1, ALK and RET genes rearrangements and the rates of BRAF, HER2 and MET gene mutations are slightly lower than the national average. EGFR, RAS and ALK genes in the NSCLC patients from Yunnan-Kweichow Plateau have high positive rates, and display different demographic and clinical characteristics, which are of great significance in the selection of targeted therapy populations.

Objective:To analyze the EGFR mutation profile of lung cancer patients in Yunnan, and to provide evidence for clinical personalized treatment.Methods:Demographic and clinical data of 2 967 lung cancer patients undergoing EGFR identification were collected and analyzed from January 2014 to August 2019 in Yunnan Cancer Hospital.Results:The proportion of EGFR mutation in 2 967 patients with lung cancer was 46.2%. Univariate analysis showed that the proportion of EGFR mutation in women was higher than that in men ( P<0.001) and displayed a downward trend with age ( P=0.03). The mutation rate of ethnic minorities was higher than Han ( P=0.012). Mutation rate in patients without smoking history was higher than those with smoking history ( P<0.001), and patients without drinking history was higher than patients with drinking history ( P<0.001). Mutation rate in patients without family history of lung cancer was higher than those with family history ( P=0.008). The mutation rate of adenocarcinoma was higher than other pathological types ( P<0.001). The mutation rate was different among stages, and it was higher in early patients than that in advanced patients ( P<0.001). The mutation rate of tissue specimens was higher than those of cytology and peripheral blood samples ( P<0.001). The mutation rate of Xuanwei area was lower than that in non-Xuanwei area ( P<0.001). Multivariate analysis showed that gender ( P<0.001), age ( P=0.036), smoking history ( P<0.001), pathological type ( P<0.001), specimen type ( P<0.001), and whether or not Xuanwei area ( P<0.001) were the independent factors of EGFR mutation.The EGFR mutation was more common in female, non-smokers, adenocarcinoma, non-Xuanwei area, tissue specimen and young lung cancer patients.The mutation types of EGFR in 1 370 cases mainly included 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area was L858R, while in non-Xuanwei area was 19-Del.The mutation rates of G719X, G719X+ L861Q, G719X+ S768I, and S768I in Xuanwei were higher while the mutation rates of 19-Del, L858R, and 20-ins were lower than non-Xuanwei area ( P<0.05). The 19-Del mutation rate of ethnic minorities is higher than that of Han ( P<0.001). The combined mutation rate of G719X, L861Q in Han was higher than that of ethnic minorities ( P=0.005). Conclusions:The EGFR mutation rate in lung cancer patients in Yunnan is similar to Asian and Chinese, and higher in female, non-smokers, adenocarcinomas, young and non-Xuanwei area patients. The most common types of EGFR mutation in Yunnan are 19-Del and L858R. The predominant mutation of EGFR in Xuanwei area is L858R, while in non-Xuanwei area is 19-Del. The mutation rates of G719X, G719X+ L861Q, G719X+ S768I and S768I are higher in Xuanwei patients than those in non-Xuanwei patients. The combined mutation rate of G719X and L861Q in Han nationality is higher than that of ethnic minorities.