Objective:To study the early predictors of refractory septic shock (RSS) in neonates.Methods:From July 2020 to December 2021, clinical data of neonates with septic shock admitted to the Neonatal Department of our hospital were retrospectively reviewed. According to the maximum septic shock score (SSS) during clinical course, the neonates were assigned into RSS group and non-RSS group. Perinatal data, laboratory results and hemodynamic parameters at diagnosis were compared between the two groups. Multiple logistic regression analysis was used to identify independent risk factors of RSS and septic shock-related death. Receiver operating characteristic (ROC) curve was constructed to evaluate the early predictors of poor prognosis.Results:A total of 130 neonates were enrolled, including 54 in RSS group and 76 in non-RSS group. Compared with the non-RSS group, the RSS group had significantly lower pH, base excess (BE), stroke volume index (SVI), cardiac output (CO) and cardiac index (CI).Meanwhile, the RSS group had significantly higher mean arterial pressure (MAP) to CI ratio (MAP/CI) and SSS [including bedside SSS (bSSS), computed SSS (cSSS) and modified version of cSSS (mcSSS)] (all P<0.05). Multiple logistic regression analysis showed that increased MAP/CI was an independent predictor of RSS. The cut-off value of MAP/CI was 11.6 [sensitivity 62%, specificity 87%, positive predictive value (PPV) 79% and negative predictive value (NPV) 77%], with an area under the curve (AUC) of 0.734. Increased mcSSS was an independent predictor of septic shock-related death. The cut-off value of mcSSS was 5.8 (sensitivity 83%, specificity 72%, PPV 21% and NPV 97%), with an AUC of 0.845. Conclusions:Increased MAP/CI (≥11.6) and mcSSS (≥5.8) may be early predictors of RSS and septic shock-related death in neonates.

Objective To analyze the occupational health status of radiation workers in Guangdong Province. Methods A total of 8 913 radiation workers who underwent occupational medical examination (OME) in Guangdong Province Hospital for Occupational Disease Prevention and Treatment in 2020 were selected as the exposure group, and 2 024 non-radiological workers who underwent health examination in the same hospital in the same period of time were selected as the control group using convenient sampling method. The study analyzed the prevalence of abnormalities in thyroid, eye lens, blood pressure, complete blood count and micronucleus in individuals of the two groups. Results The abnormal rates of eye lens, blood pressure and complete blood count in the radiation workers in the exposure group were higher than those in the control group (23.3% vs 8.0%, 18.6% vs 9.0%, 18.1% vs 8.5%, all P<0.01). However, there was no significant difference in the abnormal rates of thyroid and micronucleus in workers between these two groups (12.8% vs 11.5%, 0.1% vs 0.0%, all P>0.05). The abnormal rates of thyroid, eye lens and blood pressure in radiation workers increased with the exposure period of radiation (all P<0.05). Conclusion Long-term exposure to low-dose ionizing radiation have certain effects on the thyroid, eye lens, and blood pressure of radiation workers, with a time-effect relationship of years of radiation work.

BACKGROUND:Increased homocysteine level induces apoptosis of human umbilical vein endothelial cells,but the mechanism remains unclear. OBJECTIVE:To investigate the role of hsa-circ-0001360 in human umbilical vein endothelial cell apoptosis induced by homocysteine. METHODS:In vitro cultured human umbilical vein endothelial cells were divided into control group,homocysteine group,interference control group,interference control + homocysteine group,hsa-circ-0001360 interference group,hsa-circ-0001360 + homocysteine interference group,overexpression control group,overexpression control + homocysteine group,hsa-circ-0001360 overexpression group and hsa-circ-0001360 + homocysteine overexpression group.All groups were treated with 100 μmol/L homocysteine.After 72 hours of intervention,the expressions of apoptosis-related proteins Bax,Bcl-2,and Caspase-3 were detected by western blot assay.The apoptotic rate was detected by flow cytometry.Quantitative real-time PCR was used to detect the expression of hsa-circ-0001360. RESULTS AND CONCLUSION:(1)Compared with the control group,the expression of Caspase-3 and Bax was significantly increased(P<0.01),and the expression of Bcl-2 was significantly decreased(P<0.01),and the apoptotic rate was significantly increased(P<0.01)in the homocysteine group.(2)Compared with control group,the expression of hsa-circ-0001360 was significantly increased in the homocysteine group(P<0.01).(3)The expression of hsa-circ-0001360 was significantly higher in the cytoplasm than that in the nucleus(P<0.01).(4)Compared with the interference control C group and interference control + homocysteine group,the expressions of Caspase-3 and Bax were significantly decreased(P<0.01),while the expression of Bcl-2 was significantly increased(P<0.01);the apoptotic rate was significantly decreased(P<0.01)in sh-hsa-circ-0001360 interference group and sh-hsa-circ-0001360 + homocysteine interference group.(5)Compared with overexpression control group and overexpression control + homocysteine group,the expressions of Caspase-3 and Bax were significantly increased(P<0.01),while the expression of Bcl-2 was significantly decreased(P<0.01);the apoptotic rate was significantly increased(P<0.01)in the hsa-circ-0001360 overexpression group and the hsa-circ-0001360 + homocysteine overexpression group.(6)In conclusion,hsa-circ-0001360 can promote the apoptosis of human umbilical vein endothelial cells induced by homocysteine.

Objective To establish an allogeneic rat model of endometriosis and to evaluate the effects of gonadotropin-releasing hormone (GnRH) agonist GenSci006 on experimental rat endometriosis. Methods Endometrium from SPF grade donor female SD rats were transplanted onto the abdominal wall of recipient female rats to construct an allogeneic endometriosis model. The rats undergoing sham surgery were divided into the sham group. Three weeks later, the length, width and height of the ectopic endometrium were measured, and the volume of the endometrium (V₁) was calculated before drug administration. The modeling rats were randomly divided into four groups: model group, triptorelin group (0.25 mg/kg), GenSci006-1 group (0.125 mg/kg) and GenSci006-2 group (0.25 mg/kg). Each group had 16 rats and received a single dose of the corresponding drug. The sham group and model group were administered an equal volume of solvent. Three weeks after administration, ectopic endometrium was measured to calculate the volume V₂ and inhibition rate. The effect of GenSci006 on rat uterus and ovarian tissues was assessed by comparing organ coefficients and changes in pathological sections. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of serum estradiol (E₂), progesterone (P₄), follicle stimulating hormone (FSH), and luteinizing hormone (LH). Real-time fluorescent quantitative PCR was used to detect the expression of GnRH receptor (GnRHR) mRNA in the hypothalamus and pituitary. Western blot was used to detect the expression of estradiol receptor alpha (ERα), beta (ERβ) and progesterone receptor (PR) in ectopic endometrium. Results Three weeks after administration, compared with the model group, the body weight of rats in the triptorelin and GenSci006-2 groups significantly increased (P < 0.05), while the volume of ectopic endometrium significantly decreased (P < 0.05). Compared with the sham group, the model group showed no significant changes in uterine and ovarian organ coefficients or endometrial thickness (P > 0.05). Compared with the model group, the uterine organ coefficients and endometrial thickness were significantly reduced in the triptorelin and GenSci006-2 groups (P < 0.05). Compared with the sham group, the serum levels of E₂, P₄, FSH and LH in the model group showed no significant changes (P > 0.05). Compared with the model group, the ovarian organ coefficient and serum P₄ levels of rats in the Triptorelin, GenSci006-1, and GenSci006-2 groups were significantly reduced (P < 0.05), while the serum LH levels of rats in the GenSci006-1 group were significantly increased (P < 0.05). However, there were no significant changes in serum E₂ and FSH levels in each group (P > 0.05). Compared with the model group, the expression levels of GnRHR mRNA in the pituitary tissue of rats in the triptorelin and GenSci006-2 groups were significantly downregulated (P < 0.05), with no significantly changes in the hypothalamus (P > 0.05). There were no significant changes in the expression level of GnRHR mRNA in the hypothalamus or the protein levels of ERα, ERβ and PR in the ectopic endometrial tissue in any group (P > 0.05). Conclusion The allogeneic endometriosis rat model is a suitable animal model for screening and evaluating drugs for treating endometriosis. The volume of ectopic endometrium, inhibition rate, uterine and ovarian organ coefficients, and serum E₂ levels may serve as indicators for detecting drug efficacy.

Objective To investigate the effect of miR-22-3p on pyroptosis of vascular smooth muscle cells(VSMCs)induced by homocysteine(Hcy).Methods Human VSMCs were cultured in vitro and divided into a Control group(0 μmol/L Hey)and a Hey group(100 μmol/L Hey).After intervention,expression levels of pro Caspase-1,gasdermin D(GSDMD),N-GSDMD,and NLR family pyrin domain containing 3(NLRP3)were detected by Western blot.MiR-22-3p expression was determined by quantitative real-time reverse-transcription polymerase chain reaction.Interleukin(IL)-1 β and IL-18 levels in the supernatant were measured by enzyme-linked immunosorbent assay.Cells were also transfected with control miR-22-3p(miR-22-3p-NC),miR-22-3p-mimic,and miR-22-3p-inhibitor,to observe the effects on VSMC pyroptosis induced by Hcy.Results Expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs were increased(P＜0.05),IL-1 β and IL-18 levels were increased(P＜0.01),and the relative expression level of miR-22-3p was reduced(P＜0.01)in the Hcy group compared with the Control group.Transfection with miR-22-3p-mimic significantly decreased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01),and significantly decreased levels of IL-1β and IL-18(P＜0.01),while transfection with miR-22-3p-inhibitor significantly increased the expression levels of pro Caspase-1,GSDMD,N-GSDMD,and NLRP3 in VSMCs(P＜0.01)and significantly increased the levels of IL-1β and IL-18(P＜0.05).Conclusions MiR-22-3p may delay Hcy-induced VSMC pyroptosis.

Objective:To explore the effects of consecutively repeated application of emergency contraception pills (ECPs) containing levonorgestrel (LNG) on the female fertility and the health outcomes of F1 generation rats.Methods:Female SPF rats were intragastric administered with LNG-ECPs consecutively for 3 (P-3), 6 (P-6) and 12 (P-12) estrous cycles (three times in each estrous cycle), respectively. Under each administration schedule, rats were randomly divided into 2 groups according to body weight stratification using random numbers generated in Excel, i.e. LNG-ECPs group and solvent control group, administered with 0.12 mg/kg LNG-ECPs and corresponding volumes of 0.5% CMC-Na, respectively. Four hours after the last dosing, half of the animals (12-18) in each group were allotted randomly for dissection (6-9) and mating (6-9), respectively. The remaining half (12-18) were recovered for 3 estrous cycles, and then were randomly allocated for dissection (6-9) and mating (6-9). Organ coefficients were calculated. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, anti-Müllerian hormone (AMH) and free thyroid hormone 3 (fT3) were examined by enzyme linked immunosorbent assay (ELISA). Ovarian tissues were sectioned and stained with hematoxylin and eosin (HE) for follicle counting. In addition, the pregnancy rate and litter size of the female rats were recorded, and the growth indexes and behavioral parameters of the cubs were measured. Moreover, RNA sequencing (RNA-seq) of the ovarian tissues was performed to establish the differential expression gene profile of ovarian injury induced by LNG-ECPs. Then gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed.Results:1) After consecutive administration for 3 and 6 estrous cycles, LNG-ECPs showed no significant impact on the serum hormone levels and female fertility (all P>0.05), and the growth indexes and behavioral parameters of the F1 generation (all P>0.05). 2) After consecutive administration for 12 estrous cycles, the serum levels of FSH [(0.21±0.17) U/L], LH [(0.27±0.08) U/L] and progesterone [(0.68±0.23) μg/L] in LNG-ECPs group decreased significantly compared with those in solvent control group [(1.00±0.82) U/L, P=0.043; (1.00±0.50) U/L, P=0.006; (1.00±0.20) μg/L, P=0.027], while the level of estradiol [(2.24±1.03) μg/L] and testosterone [(1.25±0.25) μg/L] increased noticeably compared with those in solvent control group [(1.00±0.35) μg/L, P=0.019; (1.00±0.07) μg/L, P=0.044]. The number of primordial follicles (4.88±2.36) lost distinctly, while the number of atretic follicles (24.38±5.01) increased markedly in LNG-ECPs group compared with those in solvent control group (16.13±9.36, P=0.005; 19.13±2.30, P=0.018). In addition, the weight-loaded swimming (WLS) time of the F1 generation rats from the LNG-ECPs group [(157.13±32.29) s] reduced obviously compared with those from the solvent control group [(198.06±40.01) s, P=0.003]. Moreover, after recovering for 3 estrous cycles, LNG-ECPs significantly increased the levels of FSH [(2.48±1.18) U/L], LH [(1.60±0.41) U/L], testosterone [(1.37±0.23) μg/L] and the ratio of FSH/LH (1.61±0.41) compared with those in solvent control group [(1.00±0.67) U/L, P=0.024; (1.00±0.27) U/L, P=0.014; (1.00±0.18) μg/L, P=0.011; 1.00±0.49, P=0.042], respectively. Additionally, the serum levels of estradiol [(0.49±0.15) μg/L] and AMH [(0.79±0.15) μg/L] were significantly lower than those in solvent control group [(1.00±0.37) μg/L, P=0.011; (1.00±0.10) μg/L, P=0.016]. In addition, the number of primordial follicles in rats of LNG-ECPs group (6.25±5.06) were obviously less than that in solvent control group (12.00±5.56, P=0.048). Furthermore, the total distance in open field [(89.85±36.98) m] and the swimming time in WLS [(112.00±29.52) s] in rats treated with LNG-ECPs both decreased distinctly compared with those in solvent control group [(147.55±23.13) m, P<0.001; (137.69±25.85) s, P=0.014]. 3) According to transcriptomic analysis, Cd5, Cxcr1, Lexm, Fga, Mybphl and Gstm5 were the significant differential expressed genes (DEGs) in the ovarian tissues of rats. These DEGs were involved in pathways related to steroid hormone biosynthesis, including terpenoid backbone biosynthesis, ovarian steroidogenesis, cortisol synthesis and secretion. Additionally, these genes were involved in metabolic processes, such as carbon metabolism, butanoate metabolism, cysteine and methionine metabolism. And the genes were also involved in immunoregulatory processes including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptors. Conclusion:Consecutively repeated administering LNG-ECPs to the female rats in a short-term period (<12 cycles) did not demonstrate significant adverse effects on female fertility and the growth and development and the behaviors of their F1 generation cubs. However, long-term repeated treatment with LNG-ECPs (12 cycles) caused ovarian injury on female rats and showed negative impacts on the health of the F1 generation cubs, and no significant improvement was observed after recovering for 3 estrous cycles.

Objective:To explore the effects of consecutively repeated application of emergency contraception pills (ECPs) containing levonorgestrel (LNG) on the female fertility and the health outcomes of F1 generation rats.Methods:Female SPF rats were intragastric administered with LNG-ECPs consecutively for 3 (P-3), 6 (P-6) and 12 (P-12) estrous cycles (three times in each estrous cycle), respectively. Under each administration schedule, rats were randomly divided into 2 groups according to body weight stratification using random numbers generated in Excel, i.e. LNG-ECPs group and solvent control group, administered with 0.12 mg/kg LNG-ECPs and corresponding volumes of 0.5% CMC-Na, respectively. Four hours after the last dosing, half of the animals (12-18) in each group were allotted randomly for dissection (6-9) and mating (6-9), respectively. The remaining half (12-18) were recovered for 3 estrous cycles, and then were randomly allocated for dissection (6-9) and mating (6-9). Organ coefficients were calculated. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, anti-Müllerian hormone (AMH) and free thyroid hormone 3 (fT3) were examined by enzyme linked immunosorbent assay (ELISA). Ovarian tissues were sectioned and stained with hematoxylin and eosin (HE) for follicle counting. In addition, the pregnancy rate and litter size of the female rats were recorded, and the growth indexes and behavioral parameters of the cubs were measured. Moreover, RNA sequencing (RNA-seq) of the ovarian tissues was performed to establish the differential expression gene profile of ovarian injury induced by LNG-ECPs. Then gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were analyzed.Results:1) After consecutive administration for 3 and 6 estrous cycles, LNG-ECPs showed no significant impact on the serum hormone levels and female fertility (all P>0.05), and the growth indexes and behavioral parameters of the F1 generation (all P>0.05). 2) After consecutive administration for 12 estrous cycles, the serum levels of FSH [(0.21±0.17) U/L], LH [(0.27±0.08) U/L] and progesterone [(0.68±0.23) μg/L] in LNG-ECPs group decreased significantly compared with those in solvent control group [(1.00±0.82) U/L, P=0.043; (1.00±0.50) U/L, P=0.006; (1.00±0.20) μg/L, P=0.027], while the level of estradiol [(2.24±1.03) μg/L] and testosterone [(1.25±0.25) μg/L] increased noticeably compared with those in solvent control group [(1.00±0.35) μg/L, P=0.019; (1.00±0.07) μg/L, P=0.044]. The number of primordial follicles (4.88±2.36) lost distinctly, while the number of atretic follicles (24.38±5.01) increased markedly in LNG-ECPs group compared with those in solvent control group (16.13±9.36, P=0.005; 19.13±2.30, P=0.018). In addition, the weight-loaded swimming (WLS) time of the F1 generation rats from the LNG-ECPs group [(157.13±32.29) s] reduced obviously compared with those from the solvent control group [(198.06±40.01) s, P=0.003]. Moreover, after recovering for 3 estrous cycles, LNG-ECPs significantly increased the levels of FSH [(2.48±1.18) U/L], LH [(1.60±0.41) U/L], testosterone [(1.37±0.23) μg/L] and the ratio of FSH/LH (1.61±0.41) compared with those in solvent control group [(1.00±0.67) U/L, P=0.024; (1.00±0.27) U/L, P=0.014; (1.00±0.18) μg/L, P=0.011; 1.00±0.49, P=0.042], respectively. Additionally, the serum levels of estradiol [(0.49±0.15) μg/L] and AMH [(0.79±0.15) μg/L] were significantly lower than those in solvent control group [(1.00±0.37) μg/L, P=0.011; (1.00±0.10) μg/L, P=0.016]. In addition, the number of primordial follicles in rats of LNG-ECPs group (6.25±5.06) were obviously less than that in solvent control group (12.00±5.56, P=0.048). Furthermore, the total distance in open field [(89.85±36.98) m] and the swimming time in WLS [(112.00±29.52) s] in rats treated with LNG-ECPs both decreased distinctly compared with those in solvent control group [(147.55±23.13) m, P<0.001; (137.69±25.85) s, P=0.014]. 3) According to transcriptomic analysis, Cd5, Cxcr1, Lexm, Fga, Mybphl and Gstm5 were the significant differential expressed genes (DEGs) in the ovarian tissues of rats. These DEGs were involved in pathways related to steroid hormone biosynthesis, including terpenoid backbone biosynthesis, ovarian steroidogenesis, cortisol synthesis and secretion. Additionally, these genes were involved in metabolic processes, such as carbon metabolism, butanoate metabolism, cysteine and methionine metabolism. And the genes were also involved in immunoregulatory processes including cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptors. Conclusion:Consecutively repeated administering LNG-ECPs to the female rats in a short-term period (<12 cycles) did not demonstrate significant adverse effects on female fertility and the growth and development and the behaviors of their F1 generation cubs. However, long-term repeated treatment with LNG-ECPs (12 cycles) caused ovarian injury on female rats and showed negative impacts on the health of the F1 generation cubs, and no significant improvement was observed after recovering for 3 estrous cycles.

Objective To investigate the"Precision Treatment for Oncology"course,which is offered by Peking Union Medical College.The course is aiming for collecting students'opinions and suggestions to optimize the course setting and improve the teaching quality.Methods This investigation collected data by questionnaire survey and in-terviewing from Dec.2021 to Feb.2022.The questionnaire data and interview data were analysed.Results Thirty-six quantitative questionnaires and five qualitative questionnaires were included.Improving professional knowledge and personal interests were two main reasons for students to choose courses,which existed statistical differences on different aspects of course evaluation.The overall score evaluated by medical students was 9.22 and 94.4%of the students thought the course achieved the desired goal.The scores of teachers'teaching attitude,frontier and practi-cality of course content were 9.81,9.08 and 8.86 points respectively.The students hoped to increase the case analysis practice and thematic discussion activities to enrich the teaching form.Conclusions This elective course for graduate is recognized and accepted by students.More efforts are needed in future to optimize curriculum set-tings,innovate teaching methods,improve teaching quality and explore new pathways for medical graduate educa-tion matching the needs of students.

Objective:To explore the effect of quality improvement of hemodynamic monitoring on fluid overload (FO) and outcome in newborns with septic shock.Methods:Non-invasive cardiac output monitoring and functional cardiac ultrasound quality improvement program was started during January 2020 in our hospital. Neonates with septic shock admitted before and after the program were retrospectively analyzed. From January 2018 to December 2019 was pre-improvement period when fluid resuscitation was routinely performed and vasoactive drugs was selected empirically. From January 2020 to December 2021 was post-improvement period when fluid resuscitation and/or use and adjustment of vasoactive drugs were guided by hemodynamic parameters. The 24 h, 48 h, 72 h FO, duration of invasive respiratory support, vasoactive-inotropic score, septic shock score, incidences of complications and all-cause mortality were compared between the two groups.Results:A total of 284 eligible cases were enrolled, including 136 cases in pre-improvement group and 148 cases in post-improvement group. Post-improvement group had significantly lower gestational age (GA), birth weight (BW) and body weight at disease onset than pre-improvement group ( P<0.05). Incidences of 48 h and 72 h FO, fluid resuscitation volume within 72 h, pulmonary hemorrhage and periventricular leukomalacia (PVL) were significantly lower in the post-improvement group ( P<0.05). No significant differences existed in 24 h FO, other complications and all-cause mortality between the two groups ( P>0.05). No significant differences existed in GA and BW for neonates with pulmonary hemorrhage and PVL between the two groups ( P>0.05). Conclusions:Quality improvement of hemodynamic monitoring can effectively improve FO and reduce the incidences of pulmonary hemorrhage and PVL.

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.