Objective To clarify the effectiveness of QS Nd ∶ YAG laser on melasma in Chinese patients.Methods A group (n=45) of patients previously diagnosed as facial melasma were treated with QS Nd ∶ YAG laser at approximately 1 week intervals.Eleven to twenty treatments were per formed for each patient.The treatment efficacy of QS Nd ∶ YAG laser was evaluated by patients and doctors,respectively,at various time point such as before treatment,5 weeks and 10 weeks after treatment and end of the treatment.The skin melanin index and the transepidermal water loss were e valuated by the skin multifunction tester at different time point,respectively.Results Compared with untreated,the melanin index of melasma areas decreased significantly after the laser treatment for 5 weeks,10 weeks and the end of treatment.But there was no significant difference in the melanin index of normal skin areas with or without laser treatment.Compared with untreated,the transpidermal water loss of melasma areas increased significantly after the laser treatment for 5 weeks,10 weeks and end of treatment.The patients' skin became smooth,delicate,pores shrink and more flexible.In 45 melasma patients treated by QS Nd ∶ YAG laser,8 cases basically cured (17.78 ％),25 cases were markedly effective (55.56 ％),12 cases improved (24.44 ％) and only 1 case was uneffective (2.22 ％).Theoverall effective rate was 73.33 ％.Conclnsions QSNd∶ YAG laser is a useful treatment modality for Chinese women who have melasma with precise efficacy,less side effects and high safety.

Objective To investigate the effect of diabetes mellitus (DM) on adenosine postcondi-tioning-induced reduction of myocardial ischemia-reperfusion (I∕R) injury in rats. Methods Adult male Sprague-Dawley rats, weighing 230-260 g, were used in the study. Type 2 DM was induced by high-fat diet and intraperitoneal l％ streptozocin 35 mg∕kg and confirmed by fasting blood glucose concentration>16. 7 mmol∕L 72 h later. Eighteen rats with type 2 DM were divided into 3 groups (n= 6 each) using a ran-dom number table: sham operation group (DS group), I∕R group (DI∕R group) and adenosine postcondi-tioning group (DAP group). Eighteen healthy nondiabetic rats were selected and randomly divided into 3 groups (n= 6 each): sham operation group (NS group), I∕R group (NI∕R group) and adenosine postcon-ditioning group (NAP group). Myocardial I∕R was induced by 30 min occlusion of the left anterior descend-ing branch of coronary artery followed by 2 h of reperfusion. Venous blood samples were collected from the femoral vein at 2 h of reperfusion for measurement of plasma cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) concentrations (by enzyme-linked immunosorbent assay). The rats were then sacrificed im-mediately after blood sampling for determination of the myocardial ischemic area and infarct size. Results The plasma cTnI and CK-MB concentrations were significantly increased, and the percentage of myocardial infarct size was increased after myocardial I∕R in nondiabetic and diabetic rats. Adenosine postconditioning significantly decreased plasma cTnI and CK-MB concentrations and percentage of myocardial infarct size in nondiabetic and diabetic rats (P<0. 05). Compared with group NAP, the plasma concentrations of cTnI and CK-MB were significantly increased, and the percentage of myocardial infarct size was increased in group DAP (P<0. 05). Conclusion DM can weaken cardioprotection induced by adenosine postcondition-ing in rats.

Objective To evaluate the radiosensitization effect of apatinib on esophageal cancer cell line Kyse-150, and to investigate the underlying mechanism. Methods Cells were divided into four groups:control group, apatinib treatment group, X-ray radiation group, and the combination group treated with X-rays plus apatinib. The effect of apatinib with different concentrations on the cell proliferative and radiosensitivity were evaluated by CCK-8 kit and colony formation assay. Flow cytometry method was adopted to detect the effect of apatinib on cell cycle progress and apoptosis induction. Results Apatinib inhibited the proliferation of Kyse-150 cells in time-and dose-dependent manners (r=0. 89-0. 96, P<0. 05). With the increase of apatinib concentration, D0, Dq and SF2 value of Kyse-150 cells decreased and SERD0 value increased. Compared with control group, apatinib alone group, and radiation alone group, the cell apoptosis rate significantly increased in the combination group (t=12. 36, 5. 99, 15. 47,P<0. 05). Compared with control group, the percentages of cells in G2/M phase were all significantly increased in apatinib group, radiation group and combination group (t=8. 81, 39. 69, 20. 61,P<0. 05). Compared with radiation alone group and control group, the percentage of cells in S phase significantly increased in apatinib alone group and combination group(t = 6.06, 3.82,8.81,6.24,P < 0.05). Conclusions Apatinib can increase radiosensitivity of esophageal cancer cell line Kyse-150 possibly by inhibiting cell proliferation, inducing cell apoptosis and causing redistribution of cell cycle.

Objective:To observe the effect and underlying mechanism of down-regulation of VEGFA on the radiosensitivity of esophageal cancer ECA-109 cells.Methods:Esophageal cancer cells were divided into four groups: sh-VEGFA group, vector control group, X-ray plussh-VEGFA group and X-ray plus vector group. The expressions of VEGFA gene and protein were detected by qPCR and Western blot, respectively. Cell proliferation and survival was measured by CCK8 assay and cloning formation, respectively. Cell apoptosis was detected by flow cytometry, and γ-H2AX foci were detected by immune-fluorescence assay.Results:Compared with the vector group, the expression of VEGFA gene was decreased in sh-VEGFA group ( t=11.98, P<0.05), and the expression of VEGFA protein was also reduced( t=12.38, P<0.05). After VEGFA being down-regulated, the cell proliferation( A450)was obviously inhibited( t=2.78, 7.25, 21.93, 13.21, P<0.05), and the cell clone formation of the sh-VEGFA group was significantly decreased so that D0, Dqand SF2 of sh-VEGFA group were decreased( t=5.83, 8.56, 7.68, P<0.05), and SERD0and SERDqwere increased. Compared with the vector group, the apoptosis rate in the sh-VEGFA group and the X-ray group was significantly increased and further increased in the sh-VEGFA plus X-ray group( t=17.63, 22.48, 33.87, P<0.05), and the number of γ-H2AX foci in both sh-VEGFA and vector groups were significantly increased within 2 h after X-ray irradiation. At 24 h after irradiation, the number of γ-H2AX foci returned to normal level in the vector group but remained at a higher level in the sh-VEGFA group ( t=7.00, P<0.05). Conclusions:Down-regulation of VEGFA inhibits the proliferation and colony formation, promotes apoptosis and hence increases the radiosensitivity of esophageal carcinoma cells via a pathway related to DNA damage repair.

Objective:To investigate the clinical effects of acupuncture therapy on post-hemiplegia neck and shoulder pain.Methods:Eighty patients with post-stroke hemiplegia with neck and shoulder pain who received treatment in Department of Acupuncture, Massage and Physiotherapy, Zhejiang Provincial Armed Police Corps Hospital between December 2020 and June 2021 were included in this study. They were randomly assigned to undergo either conventional rehabilitation treatment and analgesic tablets (control group, n = 40) or conventional rehabilitation treatment, analgesic tablets and acupuncture therapy in combination (observation group, n = 40). Traditional Chinese medicine efficacy, western medicine efficacy, degree of neurological deficits, ability of daily living, and the incidence of adverse reactions were compared between the two groups. Results:After treatment, traditional Chinese medicine efficacy and western Chinese medicine efficacy in the observation group were significantly higher than those in the control group (87.50% vs. 52.50%, 82.50% vs. 55.00%), and the incidence of adverse reactions in the observation group was significantly lower than that in the control group (17.50% vs. 42.50%, χ2 = 21.48, 16.33, 9.12, all P < 0.05). In the control group, National Institutes of Health Stroke Scale (NIHSS) score measured after treatment was significantly lower than that measured before treatment [(7.58 ± 1.87) points vs. (14.87 ± 1.36) points, t = -9.58, P < 0.001], and Barthel Index (BI) measured after treatment was significantly higher than that measured before treatment [(53.78 ± 1.34) points vs. (37.92 ± 1.74) points, t = 6.35, P < 0.001]. In the observation group, NIHSS score measured after treatment was significantly lower than that measured before treatment [(5.44 ± 2.11) points vs. (14.51 ± 0.34) points, t = -12.69, P < 0.001], and BI measured after treatment was significantly higher than that measured before treatment [(62.02 ± 0.68) points vs. (37.73 ± 1.58) points, t = 7.45, P < 0.05]. BI post-measurement in the observation group was significantly higher than that in the control group [(62.02 ± 0.68) points vs. (53.78 ± 1.34) points, t = 4.35, P < 0.05]; NIHSS score post-measurement in the observation group was significantly lower than that in the control group [(5.44 ± 2.11) points vs. (7.58 ± 1.87) points, t = -8.48, P < 0.05]. Conclusion:Acupuncture treatment for post-hemiplegia neck and shoulder pain can markedly reduce pain in patients, improve prognosis and increase clinical efficacy.

Objective:To explore the association between polygenic risk score (PRS) and age at onset and early-onset risk of gastric cancer (GC).Methods:Gastric cancer cases from existing genome-wide association study were included, and 112 single nucleotide polymorphisms associated with GC risk were used to derive individual PRS. Analysis of variance and Pearson correlation test was used to depict the relationship between PRS and GC onset age. Cases diagnosed before 50 years old were defined as early-onset gastric cancer. Cox proportional hazard model was used to test the association between PRS and early-onset GC risk with early-onset age as the timescale and low genetic risk (PRS ≤20%) as the reference group.Results:A total of 8 629 cases, including 6 284 males (72.82%) and 2 345 females (27.18%), were included, and the mean age was (60.61±10.80) years old. The PRS was negatively correlated with age of GC onset ( r=-0.05, P<0.001). The mean age of gastric cancer cases with low, intermediate, and high genetic risk were (61.68±10.33), (60.53±10.79), (59.80±11.20), respectively. PRS was significantly associated with the risk of early-onset GC in a dose-response manner (intermediate genetic risk: HR=1.19, 95% CI: 1.03-1.39, P=0.022; high genetic risk: HR=1.44, 95% CI: 1.20-1.71, P<0.001). Conclusions:PRS may contribute to the risk of both GC and early-onset GC. PRS can be used as a measurable indicator for risk prediction for occurrence and early-onset of GC.

Objective:To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods:MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results:Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SER D0 and SER Dq value increased. Compared with control group, the percentages of cells in G 2/M phase were increased ( tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G 0/G 1 phase were decreased ( tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased ( tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation ( t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group ( t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased ( tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased ( t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased ( tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased ( t=2.90, P<0.05) in the combination group. Conclusions:PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair.

Objective:To establish the normal reference range of the ratio of fetal umbilical venous flow rate to umbilical artery pulsatility index (VAI).Methods:A total of 816 normal fetuses underwent prenatal examination and delivery were randomly selected from October 2018 to December 2020 in Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region. Fetal weight was obtained by measuring fetal biparietal diameter, head circumference, abdominal circumference, and femoral length.Umbilical venous flow (Quv) was measured. Umbilical artery pulsatility index (UA-PI) was obtained in the free segment of amniotic fluid. Quv was standardized according to fetal size to calculate the umbilical venous flow rate (nQuv) and VAI. The association between Quv, nQuv, UA-PI, VAI and the fetal gestational week were analyzed using correlation analysis. VAI was presented as ± s, the upper limit of 95% reference value and the lower limit of 5% reference value were taken as the standards of VAI increase and decrease, respectively. Twenty-six fetuses whose VAI were lower than limit of 5% and 20 fetuse whose VAI were than limit of 95% were chosed as the case group. Results:①Fetal Quv was positively correlated with gestational week ( r=0.893, P<0.001), nQuv and UA-PI were negatively correlated with gestational week ( r=-0.552, -0.827; all P<0.001), and VAI had no significant correlation with gestational week ( r=0.000, P=0.758); ②The mean, standard deviation, lower 5% reference value, and upper 95% reference value of VAI were 195.81, 55.61, 105.95, and 293.33, respectively; ③In the cases with abnormal VAI, 26 fetuses with reduced VAI, of whom there were 16 cases of maternal hypertension, and 13 cases complicated by severe preeclampsia; 1 case with 40 turns of umbilical cord torsion, 3 cases of stillbirth, 16 cases of preterm delivery, 19 cases of low neonatal birth body weight, 4 cases of 1-min Apgar score ≤7, 6 cases of umbilical artery blood pH<7.2, and 1 case without abnormalities in fetus during pregnancy and follow-up newborn. Among the 20 fetuses with increased VAI, there were 10 cases of fetal severe thalassemia, 2 cases of thalassemia, 1 case of sacrococcygeal teratoma, 1 case of portal venous shunt, 3 cases of placental chorioangioma, and 3 cases without abnormalities in fetus during pregnancy and follow-up newborn. Conclusions:The measurement and calculation of fetal VAI is simple and easy to perform. As a comprehensive index, fetal VAI remains constant in mid and late pregnancy, facilitates the follow-up of abnormal fetuses, and has potential clinical application.

Objective To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods The esophageal cancer cells, KYSE?150 and ECA?109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol／L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR?2 was measured by real?time quantitative PCR (qRT?PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme?linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p?MEK, p?ERK, JAK2, STAT3 and p?STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor?bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively.Tumor inhibition rates of different groups were calculated.And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results In the presence of 20 μmol／L and 40 μmol／L of apatinib for 24 hours, the migration cell numbers of KYSE?150 and ECA?109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33± 26.84, respectively, that were significantly lower than control group ( P＜0.05 for all). In addition, after treatment with 10 μmol／L, 20 μmol／L and 40 μmol／L of apatinib for 7 days on KYSE?150 and ECA?109, the colony formation rates were ( 65.12± 25.48)%, ( 58.19± 24.73)% and (29.10± 22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol／L and 40 μmol／L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P＜0.05). The cell cycle ratio of G2／M phase and apoptosis rate of control group and 20 μmol／L apatinib group in KYSE?150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65± 1.54)%, respectively. The corresponding ratios in ECA?109 cells were (3.44±0.57)% and (6.31±1.43)%as well as (22.64±2.36)% and (49.26± 1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G2／M phase and induced cell apoptosis in both KYSE?150 and ECA?109 cells (P＜0.05 for all). In the presence of 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the relative levels of VEGF mRNA were (42.57± 10.43)% and ( 25.69± 1.24)%, and those of VEGF?2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P＜0.05 for all). For ECA?109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P＜0.05 for all). Moreover, after treatment with 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the VEGF concentrations were ( 766.48± 114.27) pg／ml and ( 497.40± 102.18) pg／ml, which were significantly decreased compared to control group [(967.41± 57.75) pg／ml, P＜0.05)]. The results in ECA?109 were consistent (P＜0.05). Furthermore, after treatment with 40 μmol／L of apatinib in KYSE?150 and ECA?109, the relative expression of p?MEK and p?ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66± 0.07 as well as 1.03±0.20 and 1.76±0.20; P＜0.05). The relative expression of STAT3, p?STAT3 in control group and experimental group were 0.96 ± 0.15 and 0.85 ± 0.16 as well as 0.62 ± 0.09 and 0.36 ± 0.13, respectively. The results showed that the protein levels of STAT3 and p?STAT3 were significantly lower than the control group (P＜0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg／ml, (16.40 ± 2.81) pg／ml and ( 15.04 ± 4.88) pg／ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras／Raf／MEK／ERK pathway and JAK2／STAT3 pathway.

Objective To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods The esophageal cancer cells, KYSE?150 and ECA?109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol／L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR?2 was measured by real?time quantitative PCR (qRT?PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme?linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p?MEK, p?ERK, JAK2, STAT3 and p?STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor?bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively.Tumor inhibition rates of different groups were calculated.And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results In the presence of 20 μmol／L and 40 μmol／L of apatinib for 24 hours, the migration cell numbers of KYSE?150 and ECA?109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33± 26.84, respectively, that were significantly lower than control group ( P＜0.05 for all). In addition, after treatment with 10 μmol／L, 20 μmol／L and 40 μmol／L of apatinib for 7 days on KYSE?150 and ECA?109, the colony formation rates were ( 65.12± 25.48)%, ( 58.19± 24.73)% and (29.10± 22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol／L and 40 μmol／L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P＜0.05). The cell cycle ratio of G2／M phase and apoptosis rate of control group and 20 μmol／L apatinib group in KYSE?150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65± 1.54)%, respectively. The corresponding ratios in ECA?109 cells were (3.44±0.57)% and (6.31±1.43)%as well as (22.64±2.36)% and (49.26± 1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G2／M phase and induced cell apoptosis in both KYSE?150 and ECA?109 cells (P＜0.05 for all). In the presence of 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the relative levels of VEGF mRNA were (42.57± 10.43)% and ( 25.69± 1.24)%, and those of VEGF?2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P＜0.05 for all). For ECA?109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P＜0.05 for all). Moreover, after treatment with 20 μmol／L and 40 μmol／L of apatinib in KYSE?150 cells, the VEGF concentrations were ( 766.48± 114.27) pg／ml and ( 497.40± 102.18) pg／ml, which were significantly decreased compared to control group [(967.41± 57.75) pg／ml, P＜0.05)]. The results in ECA?109 were consistent (P＜0.05). Furthermore, after treatment with 40 μmol／L of apatinib in KYSE?150 and ECA?109, the relative expression of p?MEK and p?ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66± 0.07 as well as 1.03±0.20 and 1.76±0.20; P＜0.05). The relative expression of STAT3, p?STAT3 in control group and experimental group were 0.96 ± 0.15 and 0.85 ± 0.16 as well as 0.62 ± 0.09 and 0.36 ± 0.13, respectively. The results showed that the protein levels of STAT3 and p?STAT3 were significantly lower than the control group (P＜0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg／ml, (16.40 ± 2.81) pg／ml and ( 15.04 ± 4.88) pg／ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras／Raf／MEK／ERK pathway and JAK2／STAT3 pathway.