OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Image 1.

Objective:To evaluate the development of fetal cerebral sulci and gyrus and the blood perfusion in pregnant women with gestational diabetes mellitus(GDM) by ultrasound.Methods:A total of 1 540 pregnant women with 28-34 weeks of pregnancy who underwent systematic screening in Henan Provincial People′s Hospital from January 2022 to October 2022 were prospectively selected, 100 pregnant women with GDM were selected as the GDM group. According to the effect of blood glucose control, the GDM group was divided into 2 groups: the satisfied control group (GDM group 1), and the dissatisfied control group (GDM group 2), with 50 cases in each group. At the same period, 50 healthy pregnant women at 28-34 weeks of gestation were enrolled as the control group. The differences of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci among the 3 groups were statistically analyzed. And the correlations between the deep of the brain cerebral sulci and gyrus and controlled blood glucose levels were evaluated. The umbilical artery pulsation index(UAPI), middle cerebral artery pulsation index(MCAPI) and ductus venosus pulsation index(DVPI) among the 3 groups were compared, and the differences in fetal blood perfusion among the 3 groups were evaluated.Results:There were no significant differences in the depths of the sylvian fissure, parietooccipital sulci, calcarine sulci and cinguli sulci between the control group and the GDM group 1 (all P>0.05), and they were larger than those of the GDM group 2 (all P<0.05). The depths of lateral fissure, parieto-occipital sulcus, cingulate sulcus and calcarine sulcus were negatively correlated with fasting blood glucose, 1 h and 2 h postprandial blood glucose (all P<0.05). There were no significant differences in MCAPI, UAPI and DVPI between the control group and GDM1 group (all P>0.05). The MCAPI in GDM 2 group was lower than that in the control group and GDM 1 group, and the UAPI and DVPI values were higher than those in the control group and GDM1 group(all P<0.05). Conclusions:The maturity of fetal cerebral sulci and gyrus in GDM pregnant women is related to the blood glucose control of pregnant women. The change of blood perfusion caused by persistent hyperglycemia in pregnant women and intrauterine hypoxia may cause the development retardation of cerebral sulci and gyrus.

Objective:To investigate the effects of carnosine(CAR)on the spatial learning and memory abilities of rats with vascular cognitive impairment(VCI),and to explore the roles of the Akt/mTOR pathway and autophagy in this process.Methods:Fifty male Sprague-Dawley(SD)rats were randomly divided into sham-operated(Sham)group,VCI group,VCI+CAR-L group,VCI+CAR-M group,and VCI+CAR-H group.The spatial learning and memory abilities of rats were evaluated by the Morris water maze experiment;Nissl staining was used to detect the damage in the hippocampal CA1 region;the nitroblue tetrazolium and thiobarbituric acid methods were used to measure the activities of superoxide dismutase(SOD)and malondialdehyde(MDA)content in hippocampal tissue;Western Blot was performed to determine the expression of p-Akt,p-mTOR,Beclin-1,and LC3B proteins,and immunofluorescent staining was con-ducted to detect changes in LC3B expression in the CA1 region.SH-SY5Y cells were divided into control group,oxy-gen-glucose deprivation/reperfusion(OGD/R)group,OGD/R+rapamycin(RAPA),OGD/R+CAR(1.2 mmol/L)group,and OGD/R+CAR+RAPA group.Methyl thiazolyl tetrazolium assay was used to detect neuronal survival rate;Western Blot was used to detect the levels of p-mTOR,Beclin-1,and LC3B in neuronal cells;immunofluorescent stai-ning was performed to assess the degree of autophagy.Results:CAR could improve the learning and memory abilities of VCI rats,reduce hippocampal tissue cell damage,and inhibit oxidative stress(P＜0.01).CAR increased the expres-sion of p-Akt,p-mTOR,and p62 proteins(P＜0.01 or P＜0.05)and decreased the expression of Beclin-1 and the ra-tio of LC3B Ⅱ/Ⅰ(P＜0.01 or P＜0.05).CAR significantly increased the survival rate of SH-SY5Y cells after OGD/R(P＜0.01)and inhibited autophagy in hippocampal neurons.Furthermore,the intervention with RAPA counteracted the therapeutic effect of CAR,reduced the survival rate of SH-SY5Y groups(P＜0.01),and enhanced autophagy.Conclusion:CAR can improve rat VCI injury,and its mechanism may involve inhibiting oxidative stress,activating the Akt/mTOR signaling pathway in neuronal cells,and thereby inhibiting excessive autophagy to exert a protective effect.

Objective:To investigate the effects of carnosine(CAR)on the spatial learning and memory abilities of rats with vascular cognitive impairment(VCI),and to explore the roles of the Akt/mTOR pathway and autophagy in this process.Methods:Fifty male Sprague-Dawley(SD)rats were randomly divided into sham-operated(Sham)group,VCI group,VCI+CAR-L group,VCI+CAR-M group,and VCI+CAR-H group.The spatial learning and memory abilities of rats were evaluated by the Morris water maze experiment;Nissl staining was used to detect the damage in the hippocampal CA1 region;the nitroblue tetrazolium and thiobarbituric acid methods were used to measure the activities of superoxide dismutase(SOD)and malondialdehyde(MDA)content in hippocampal tissue;Western Blot was performed to determine the expression of p-Akt,p-mTOR,Beclin-1,and LC3B proteins,and immunofluorescent staining was con-ducted to detect changes in LC3B expression in the CA1 region.SH-SY5Y cells were divided into control group,oxy-gen-glucose deprivation/reperfusion(OGD/R)group,OGD/R+rapamycin(RAPA),OGD/R+CAR(1.2 mmol/L)group,and OGD/R+CAR+RAPA group.Methyl thiazolyl tetrazolium assay was used to detect neuronal survival rate;Western Blot was used to detect the levels of p-mTOR,Beclin-1,and LC3B in neuronal cells;immunofluorescent stai-ning was performed to assess the degree of autophagy.Results:CAR could improve the learning and memory abilities of VCI rats,reduce hippocampal tissue cell damage,and inhibit oxidative stress(P＜0.01).CAR increased the expres-sion of p-Akt,p-mTOR,and p62 proteins(P＜0.01 or P＜0.05)and decreased the expression of Beclin-1 and the ra-tio of LC3B Ⅱ/Ⅰ(P＜0.01 or P＜0.05).CAR significantly increased the survival rate of SH-SY5Y cells after OGD/R(P＜0.01)and inhibited autophagy in hippocampal neurons.Furthermore,the intervention with RAPA counteracted the therapeutic effect of CAR,reduced the survival rate of SH-SY5Y groups(P＜0.01),and enhanced autophagy.Conclusion:CAR can improve rat VCI injury,and its mechanism may involve inhibiting oxidative stress,activating the Akt/mTOR signaling pathway in neuronal cells,and thereby inhibiting excessive autophagy to exert a protective effect.

Objective:To analyze the genetic etiology and prognosis in fetuses with increased nuchal translucency (NT) in order to assist in the clinical prenatal genetic counseling and diagnosis.Methods:This study retrospectively enrolled 1 658 cases of singleton pregnancy (<35 years old) receiving invasive prenatal diagnosis, including karyotype analysis and/or chromosome microarray analysis or copy number variation (CNV) sequencing, due to NT value ≥2.5 mm in the first trimester in Henan Provincial People's Hospital from August 2014 to December 2021. They were divided into different groups according to the thickness of NT (≥2.5-<3.0, ≥3.0-<3.5, ≥3.5-<4.5, ≥4.5-<5.5, ≥5.5-<6.5 and ≥6.5 mm groups) and abnormal ultrasound findings (isolated increased NT group, increased NT complicated by soft markers/non-severe structural abnormality group and increased NT complicated by severe structural abnormality group). The results of invasive prenatal diagnosis and pregnancy outcomes were compared between different groups using Chi-square test and trend Chi-square test. Results:The detection rates of numerical abnormalities of chromosomes were 15.8% (262/1 658) and 17.6% (252/1 431) when the NT thickness cut-off value were 2.5 mm or 3.0 mm, respectively. Overall, the detection rate of numerical abnormalities of chromosomes increased with thickness of NT ( χ2trend=180.75, P<0.001), ranging from 6.6% (44/671) in the NT≥2.5-<3.5 mm group to 45.6% (113/248) in the NT≥5.5 mm group. The incidence of pathogenic/likely pathogenic CNV(P/LP CNV) did not increased with NT thickness ( χ2trend=3.26, P=0.071), and the highest detection rate was observed in the NT≥4.5-<5.5 mm group (9.0%, 19/211). The detection rate of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥2.5-<3.0 mm group and NT≥3.0-<3.5 mm group were 5.3% (10/188) and 9.6% (36/375), respectively, however, the difference was not statistically significant ( χ2=3.06, P=0.080). The detection rates of numerical abnormalities of chromosomes plus P/LP CNV in the isolated NT≥3.5-<4.5 mm group and NT≥2.5-<3.0 mm complicated by soft markers/ non-severe structural abnormality group were 12.7% (52/410) and 24.1% (7/29), respectively, and the risk were 2.6 times (95% CI: 1.3-5.2) and 5.7 times (95% CI: 2.0-16.4) of the isolated NT≥2.5-<3.0 mm group, respectively. The pregnancy termination rate increased with the NT thickness ( χ2trend=304.42, P<0.001), ranging from 10.8% (23/212) in the NT≥2.5-<3.0 mm group to 90.7% (117/129) in the NT≥6.5 mm group. After exclusion of the pregnancies terminated due to numerical abnormalities of chromosomes and P/LP CNV, 87.6% (862/984) of the fetus with increased NT were born alive. Conclusions:The detection rate of numerical abnormalities of chromosomes increases with the thickness of NT. Invasive prenatal diagnosis is required for non-advance aged singleton pregnant women when fetuses present with isolated NT≥2.5 mm with or without soft markers/structural abnormalities.

Objective To observe the effect of transcutaneous electrical acupoint stimulation(TEAS)on circulation depression in patients underwent thoracoscopic radical resection of lung cancer under general anesthesia combined with thoracic paravertebral block(TPVB).Methods A total of 150 patients from Octomber 2021 to May 2022,58 males and 92 females,aged 19-64 years,BMI 18-30 kg/m2,ASA physical status Ⅰ or Ⅱ,underwent thoracoscopic radical resection of lung cancer under general anesthesia combined with TPVB were enrolled.According to random number table method,the patients were divided into two groups:the TEAS group and the control group,75 patients in each group.In the TEAS group,transcutaneous electrical acupoint stimulation was performed at Hegu,Neiguan,and Zusanli 30 minutes be-fore induction until the end of operation.In the control group,the electrodes were only connected at the same time point without electrical stimulation.HR,SBP,DBP,MAP,and BIS were recorded before stimu-lation(T0),10 minutes after TPVB(T1),the time of skin incision(T2),30 minutes after operation star-ted(T3),60 minutes after operation started(T4),the end of operation(T5),and 30 minutes after opera-tion(T6).The incidences of bradycardia,tachycardia,hypotension,and hypertension,and the usages of vasoactive drugs during operation were recorded.The dosages of propofol,sufentanil,and remifentanil in the operation were recorded.The VAS pain score 1,2,and 7 days after operation,the usages of analgesics used within 7 days after operation,postoperative adverse effects such as nausea and vomiting,dizziness,chest tightness,and shortness of breath,and the length of hospital stay were recorded.Results Compared with the control group,intraoperative infusion volume,incidence of hypotension,hypertension,and circulation depression,the usages of deoxyepinephrine,ephedrine,norepinephrine,and urapidil intraoperation,VAS pain scores 1 and 2 days after operation,and the usage of analgesics within 7 days after operation were sig-nificantly decreased(P＜0.05),length of hospital stay was significantly shortened(P＜0.05),SBP,DBP,and MAP were significantly increased at T1(P＜0.05),the dosagesof propofol,sufentanil,and remifentanil were significantly decreased in the TEAS group(P＜0.05).There were no significantly differ-ences of nausea and vomiting,dizziness,and shortness of breath between the two groups.Conclusion TEAS can improve the circulation depression,and reduce the incidences of intraoperative hypotension and hypertension,decrease the dosages of anesthetics and the rate of using vasoactive drugs during operation,improve early postoperative acute pain and shorten the length of hospital stay in patients undergoing thoraco-scopic radical resection of lung cancer under general anesthesia combined with TPVB.

Objective:To investigate the normal parameter values of transvaginal E-Cervix cervical elastography of primipara and explore the correlation between E-Cervix parameters and gestational age.Methods:A total of 301 primiparas underwent E-Cervix by transvaginal ultrasound in Henan Provincial People′s Hospital from March 2019 to January 2021, they were divided into 6 groups according to generational weeks: group A (11-13 + 6W), group B (14-17 + 6W), group C (18-21 + 6W), group D (22-25 + 6W), group E (26-29 + 6W), group F (30-33 + 6W). Real-time E-Cervix parameters were obtained, including elasticity contrast index (ECI), hardness ratio (HR), internal ostium (IOS), and external ostium (EOS), strain ratio of the internal and external cervical ostium (IOS/EOS), and the correlations between E-Cervix parameters and the gestational week were analyzed. Results:The normal reference ranges of parameters ECI, IOS, EOS, HR and IOS/EOS were obtained, their 95% reference values in groups A to F were as follows: ECI (1.84-3.38, 2.13-4.50, 2.25-4.12, 2.06-3.96, 2.04-5.15, 2.36-5.53), HR (85.85%-88.72%, 77.31%-80.92%, 74.41%-78.50%, 71.13%-74.35%, 64.49%-68.56%, 63.57%-68.23%), IOS (0.12-0.21, 0.14-0.34, 0.14-0.31, 0.19-0.40, 0.19-0.56, 0.21-0.49), EOS (0.12-0.30, 0.14-0.34, 0.16-0.41, 0.20-0.39, 0.22-0.58, 0.22-0.54), IOS/EOS (0.55-1.12, 0.52-1.45, 0.56-1.26, 0.54-1.38, 0.54-1.52, 0.65-1.46). The differences of ECI, HR, IOS and EOS in different groups were statistically significant (all P<0.05). Spearman correlation analysis results showed that ECI, IOS, and EOS were positively correlated with gestational week( rs=0.524, 0.689, 0.609; all P<0.01). HR was negatively correlated with gestational week ( rs=-0.755, P<0.01). The regression equations of ECI, HR, IOS and EOS were Y=0.06X+ 52.214, Y=99.25-1.07X, Y=8.63E-3X+ 0.05, Y=7.94E-3X+ 0.1, respectively. Conclusions:The normal parameters values of E-TVES are summarized.It provides effective support in data for cervical evaluation in the preterm prediction and success of labor induction.

Objective: To compare the consistency of thyroid stimulating hormone (TSH) results from four chemiluminescence assays. Methods: A total of 102 fresh serum samples from Peking Union Medical College Hospital during March 2018 and April 2018 were collected for precision evaluation and methodological comparison referring to CLSI EP15-A2 and EP9-A2 protocols. The levels of serum TSH were detected by Abbott i2000 (system A), Beckman DXI800 (system B), Siemens ADVIA Centaur XP (system C) and Roche e601 (system D) automatic chemiluminescence analyzers and their matching reagents, respectively. The obtained results were compared with the passing-bablok and Bland Altman methods. Taking 0.27 μIU/mL and 5.33 μIU/mL as the medical decision level, the expected bias of each detection system was compared. Results: The precisions of systems A,B,C and D were 1.7%-3.3%， 2.3%- 3.9%，0.7%-2.3% and 0.6%-1.5%,respectively. The median (P 25,P 75) of TSH concentrations detected by systems A,B,C and D were 1.898 (0.518,4.809)μIU/mL, 2.819 (0.719,7.020)μIU/mL,2.502 (0.692,6.888)μIU/mL and 3.105 (0.886, 7.905)μIU/mL, respectively. The coefficients of determination (R 2 ) of regression equation were above 0.975 for 4 detection systems. The correlation coefficients (r), intercepts and slopes of 4 detection systems were 0.993 5-0.997 1, 0-0.06 and 0.59-1.15, respectively, and systems B and C had the best correlations with 1.02 of slope and 0 of intercept. The deviation plot showed that the bias% of 4 detection systems was between -48.1% and 17.3%. Among them, systems A and D had the largest bias, while systems B and C had the lowest bias. The expected bias of 4 detection systems at the medical decision level was -40.7%-37.2%. Conclusion The consistency between Beckman and Siemens TSH detection systems is good, while those of Roche and Abbott TSH detection systems are different from the other two.

Objective To explore the value of sonohysterography (SHG) in diagnosis of post-cesarean scar diverticulum.Methods Totally 28 patients with post-cesarean scar diverticulum suspected clinical underwent SHG and conventional transvaginal ultrasound (TVS).The sizes of the diverticulum and the thickness of muscular layer were observed and the diagnostic value of SHG and TVS were compared.All patients underwent hysteroscopy,and the results were considered as diagnostic standard.Results Twenty diverticulums were found by hysteroscopy,20 diverticulums by SHG and 17 diverticulums by TVS.Taking hysteroscopy as diagnostic standard,the accuracy of SHG,TVS in diagnosis of diverticulums were 100％ (20/20) and 89.29％ (17/20) respectively.Superoinferior diameter ([9.17 ± 2.63] mm),left-right diameter ([11.76± 5.67]mm) of diverticulum and thickness of muscular layer ([3.29 ± 1.01]mm) measured by TVS had statistical differences compared with those measured by SHG (superoinferior diameter:[12.01± 4.04]mm,left-right diameter:[12.37±6.14]mm,thickness:[2.85±1.30]mm,all P＜0.05).The altitude of diverticulum measured by TVS and SHG had no statistial difference ([5.62±± 2.13]mm vs [5.50±2.34]mm,P＞0.05).Five patients with intra uterine adhesions,4 with endometrial polyps and 1 with submucosal myoma were detected by SHG.Conclusion SHG has clinical value in di agnosis of post-cesarean scar diverticulum..