Objective:To investigate the incidence and risk factors of hypertensive disorders in pregnancy (HDP) in high altitude areas and their influence on maternal and infant outcomes.Methods:This was a retrospective case-control study. A total of 220 newborns were selected as the high altitude group, who were born to 216 mothers with HDP and admitted to the Neonatal Intensive Care Unit of the Lhasa People's Hospital from June 1, 2018, to June 1, 2020. The low altitude group consisted of 235 newborns born to 231 mothers with HDP and admitted to the Department of Neonatology of the Children's Hospital Affiliated to Beijing Capital Institute of Pediatrics from January 1, 2018, to December 31, 2021. Differences in the types of HDP between the two groups and the risk factors for the high incidence of preeclampsia-eclampsia and early-onset preeclampsia in high altitude area were analyzed. The influences of HDP in high and low altitude areas on maternal and infant outcomes were compared. Statistical analysis was performed using t-test, Mann-Whitney U test, Pearson Chi-square test, or continuous correction Chi-square test, and univariate and multivariate logistic regression analysis. Results:Maternal age and the proportions of primiparae and women of advanced age or having irregular prenatal examination were greater in the high altitude group than those in the low altitude group (all P<0.05). Besides, the incidence of early-onset preeclampsia, eclampsia, preeclampsia-eclampsia, and chronic hypertension complicated by preeclampsia were also higher in the high altitude group (all P<0.05). Multivariate logistic regression analysis showed that high altitude was a risk factor for the development of preeclampsia-eclampsia ( OR=4.437, 95% CI:2.582-7.626). Adverse pregnancy history ( OR=2.576, 95% CI:1.217-5.452) and irregular prenatal examination ( OR=2.862, 95% CI:1.412-5.800) were independent risk factors for early-onset preeclampsia in pregnant women in high altitude areas. Twin-pregnancy was a protective factor for early-onset preeclampsia in pregnant women in high altitude areas ( OR=0.183, 95% CI: 0.054-0.623). The incidence of maternal heart failure [7.9% (17/216) vs 0.4% (1/231), χ2=15.98], placental abruption [7.9% (17/216) vs 3.5% (8/231), χ2=4.11], hemolysis, elevated liver function and low platelet count syndrome [14.4% (31/216) vs 1.7% (4/231), χ2=24.64], premature delivery [86.1% (118/216) vs 73.6% (170/231), χ2=10.79], fetal growth restriction [52.3% (115/220) vs 18.7% (44/235), χ2=56.26], fetal distress [18.2% (40/220) vs 8.1% (19/235), χ2=10.26], neonatal asphyxia [29.5% (65/220) vs 11.1% (26/235), χ2=24.26], severe asphyxia [8.6% (19/220) vs 2.6% (6/235), χ2=8.10] and the proportion of neonates requiring mechanical ventilation within 24 h after birth [69.5% (153/220) vs 42.6% (100/235), χ2=33.54] as well as neonatal death within 7 d after birth [5.5% (12/220) vs 1.3% (3/235), χ2=6.22] in the high altitude group were significantly higher than those in the low altitude group (all P<0.05). Conclusion:High altitude is a risk factor for preeclampsia-eclampsia, and the adverse effects of HDP on mothers and infants are more severe in high altitude areas.

Objective:To investigate an accurate and quantitative method to measure the eyeball morphological parameters of guinea pigs through a method that combines programmed digital techniques and mathematical geometric principles.Methods:Twenty-two three-week-old clean-grade male tricolor guinea pigs were selected and sacrificed by anesthesia overdose.Eyeballs were enucleated.The horizontal and sagittal images of the eyeball were taken with the high-speed photographic model of 13 million pixels macro meter, and the pictures were imported into pycharm programming software.Using the pre-written analysis program of Python 3.9, the conversion coefficient between the photo pixel and the actual length was obtained by a scale, and then the corneal surface was fitted by arc fitting and conic curve fitting.The results of arc fitting were converted to calculate the corneal radius of curvature.The corneal eccentricity was calculated according to the general conic equation (Ax 2+ Bxy+ Cy 2+ Dx+ Ey+ F=0). The corneal asphericity was evaluated by curve fitting between the central 3-mm and the whole cornea.The use and care of the animals complied with Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Shanghai Public Health Clinical Center (No.2022-A009-01). Results:The digital method of Python programming can show the corneal contour of guinea pigs completely and clearly.In the transverse plane, there was no significant difference in the corneal curvature measurements among the digital fitting in central 3-mm cornea, digital fitting in whole cornea and curvature meter ( F=1.693, P=0.190). In the sagittal plane, there was a significant difference in the corneal curvature measurements among the three methods ( F=3.500, P=0.030), and the corneal curvature measurements of the whole cornea measured by the curvature meter were significantly greater than those measured by the digital fitting ( P<0.05). There was no statistical significance in the measurements of corneal curvature radius among the three methods in the transverse plane and the sagittal plane ( F=1.817, P=0.170; F=2.050, P=0.133). The horizontal and sagittal corneal eccentricity measured by digital fitting in central 3-mm cornea were 0.55±0.15 and 0.53±0.17, which were lower than 0.66±0.10 and 0.64±0.14 measured by digital fitting in whole cornea, and the differences were statistically significant ( t=-4.860, -5.210; both at P<0.01). Conclusions:It is feasible to use Python programming digital method to measure the corneal curvature and eccentricity of guinea pigs.

Objective:To analyze the risk factors and clinical features of premature infants with bronchopulmonary dysplasia(BPD)at high altitude in Tibet and low altitude in Beijing.Methods:A retrospective case-control study was conducted.The clinical data of children with gestational age ≤32 weeks admitted to the Department of Neonatology of Lhasa People′s Hospital(altitude of 3 600 m)and the Department of Neonatology of Children′s Hospital Affiliated to Capital Institute of Pediatrics(altitude of 50 m)from January 1, 2018 to December 31, 2021 were collected.Cases were divided into BPD group and non-BPD group.Premature infants with BPD were divided into high altitude group and low altitude group according to different altitudes.The clinical characteristics and high risk factors of BPD were analyzed.Results:There were 379 premature infants with gestational age ≤32 weeks, 351 were included in the study, including 110 cases in group and 241 cases in non-BPD group.There were 48 cases in high altitude group and 62 cases in low altitude group.The incidence of BPD in high altitude areas(Lhasa)was 38.7%(48/124), among which mild, moderate and severe BPD accounted for 75.0%(36 cases), 18.8%(9 cases)and 6.3%(3 cases), respectively.The incidence rates of BPD were 100%(2/2), 86.7%(13/15)and 38.7%(33/107) in gestational age <28 weeks, 28 to 29 + 6 weeks and 30 to 32 weeks, respectively.There was a statistically significant difference among different gestational age groups( χ2=19.696, P<0.001). The incidence of BPD in low altitude areas(Beijing)was 27.3%(62/227), among which mild, moderate and severe BPD accounted for 74.2%(46 cases), 4.8%(3 cases)and 21.0%(13 cases), respectively.The incidence rates of BPD in gestational age<28 weeks, 28 to 29 + 6 weeks and 30 to 32 weeks were 100%(15/15), 45.6%(36/79)and 8.3%(11/133), respectively.There was a statistically significant difference among different gestational age groups( χ2=77.474, P<0.001). The incidence of BPD in high altitude areas was significantly higher than that in low altitude areas( χ2=4.841, P=0.028). Multivariate regression analysis showed that high altitude( OR 146.893, 95% CI 19.044-1 133.064), birth weight( OR 0.996, 95% CI 0.993-0.999), asphyxia( OR 4.187, 95% CI 3.020-21.670), non-invasive mechanical ventilation( OR 1.171, 95% CI 1.106-1.240)and invasive mechanical ventilation( OR 1.198, 95% CI 1.065-1.347)were significantly correlated with the occurrence of BPD.The gestational age at birth, small for gestational age infant, the fraction of inspired oxygen and the incidence of pregnancy induced hypertension in pregnant women in high altitude group were higher than those in low altitude group( P<0.05). The incidence of patent ductus arteriosus, the use time of noninvasive and invasive mechanical ventilation, the length of hospital stay, the age of mother, the application of prenatal hormone and the twin ratio in high altitude group were significantly lower than those in low altitude group( P<0.05). Conclusion:High altitude in Tibet is a high-risk factor for the occurrence of BPD in preterm infants.Strengthening maternal health care in high altitude areas of Tibet and doing a good job in asphyxia resuscitation in delivery room may be important measures to reduce BPD in preterm infants.

Objective:To investigate the relationship between the mechanism of exogenous hydrogen sulfide (H 2S)-induced reduction of apoptosis in neurons during focal cerebral ischemia-reperfusion (I/R) and PINK1/Parkin pathway-mediated mitochondrial autophagy in rats. Methods:Two hundred and sixteen healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 250-270 g, were divided into 4 groups ( n=54 each) using a random number table method: control group (group C), I/R group, H 2S group and H 2S plus 3-methyladenine (3-MA) group (H 2S+ 3-MA group). Focal cerebral ischemia was induced by middle cerebral artery occlusion in anesthetized rats.In group H 2S+ 3-MA, 3-MA 10 mg/kg was intraperitoneally injected at 15 min before the onset of reperfusion, while the equal volume of normal saline was given instead in the other groups.In H 2S and H 2S+ 3-MA groups, 0.25% NaSH (a donor of exogenous H 2S) 10 mg/kg was intraperitoneally injected at the onset of reperfusion, while the equal volume of normal saline was given instead in the other groups.At 1, 3 and 7 days of reperfusion, neural function was scored, and corner test (the percentage of left turn was calculated) was performed.Brains were removed and brain tissues were obtained for determination of the cerebral infarct size, Bax, Bcl-2 and caspase-3 positive cells, cell apoptosis, and expression of mitophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), PINK1 and Parkin (by Western blot). The percentage of cerebral infarct size, rate of Bax, Bcl-2 and caspase-3 positive cells and apoptosis rate were calculated.The ratio of LC3-Ⅱexpression to LC3-Ⅰexpression (LC3-Ⅱ/LC3-Ⅰ) was also calculated. Results:Compared with group C, the neural function score was significantly decreased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax, Bcl-2 and caspase-3 positive cells, apoptosis rate of neurons, and LC3-Ⅱ/LC3-Ⅰ were increased, and the expression of PINK1 and Parkin was up-regulated at each time point of reperfusion in group I/R ( P<0.05). Compared with group I/R, the neural function score and rate of Bcl-2 positive cells were significantly increased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax and caspase-3 positive cells, and apoptosis rate of neurons were decreased, the expression of PINK1 and Parkin was up-regulated, and LC3-Ⅱ/LC3-Ⅰ were increased at each time point of reperfusion in group H 2S ( P<0.05), and no significant change was found in the parameters mentioned above in group H 2S+ 3-MA ( P>0.05). Compared with group H 2S, the neural function score and rate of Bcl-2 positive cells were significantly decreased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax and caspase-3 positive cells, and apoptosis rate of neurons were increased, the expression of PINK1 and Parkin was down-regulated, and LC3-Ⅱ/LC3-Ⅰ was decreased at each time point of reperfusion in H 2S+ 3-MA group ( P<0.05). Conclusion:The mechanism by which exogenous H 2S inhibits apoptosis in neurons during focal cerebral I/R is related to enhancing mitochondrial autophagy mediated by the PINK1/Parkin pathway in rats.

The special nucleic acid fragments, 5' untranslated region (5' UTR) and internal ribosome entry site (IRES) of foot-and-mouth disease virus (FMDV), which interact with the capsid proteins, were selected as scaffolds to investigate the assembly efficiency of foot-and-mouth disease (FMD) virus-like particles (VLPs). The assembled product was characterized by evaluation of particle size, surface potential, gel retardation assay, nuclease digestion experiments, size-exclusion chromatography, transmission electron microscopy and circular dichroism analysis. The results confirmed that the 5' UTR and IRES of FMDV co-assembled with the FMD VLPs and facilitated the assembly efficiency of FMD-VLPs. It demonstrates that the assembly efficiency of 75S particles of VLPs-5'UTR was significantly higher than those of the VLPs (P<0.001) and VLPs-IRES group (P<0.01). Comparatively the assembly efficiency of 12S particles of VLPs-IRES was significantly higher than those of the VLPs (P<0.000 1) and VLPs-5'UTR (P<0.000 1). It showed that the 5' UTR represented more effective in facilitating the assembly of VLPs. This study proposes an optimized strategy for improving the assembly efficiency of VLPs for the development of VLPs vaccine.
5' Untranslated Regions ; Capsid Proteins/metabolism* ; Foot-and-Mouth Disease Virus/physiology* ; Internal Ribosome Entry Sites ; Nucleic Acids/metabolism* ; Virus Assembly

OBJECTIVE: To analyze the clinical presentation and gene of 2 pedigrees with suspected oculocutaneous albinism(OCA), and provide basis for clinical classification, genetic counseling and prenatal diagnosis. METHODS: Variants were identified using next-generation sequencing(NGS) and confirmed by Sanger sequencing in 2 pedigrees with suspected OCA. The pathogenicity of the variants was analyzed according to the American College of Medical Genetics and Genomics (ACMG) standard. RESULTS: Two compound heterozygous mutations of TYR and OCA2 genes were identified respectively in 2 pedigrees with suspected OCA. The mutation of c.819+3insATATGCC in TYR and the mutation of c.1870G>C in OCA2 are first reported in this study. The pathogenicity analysis shows that two novel mutations are likely pathogenic by combination of prediction of SIFT, Polyphen-2 and Human Splicing Finder. CONCLUSION The findings of this study expand the mutational spectrum of OCA. Compound heterozygous mutations in the TYR and OCA2 gene may be responsible for clinical manifestations of 2 pedigrees with suspected OCA.
Albinism, Oculocutaneous ; DNA Mutational Analysis ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Membrane Transport Proteins ; Monophenol Monooxygenase ; Mutation ; Pedigree ; Pregnancy

Objective: To investigate the position and the size of ureteral stone in patients before treated with ureteroscopic lithotripsy or percutaneous nephrolithotomy (PCNL), as well as the dilatation of ureter caused by stone, which may be helpful for better understanding of pathogenesis of ureteral stone and improvement of the diagnosis and treatment in clinic.Methods: A total of 129 cases with ureteral stone for endourologic lithotripsy in Peking University People''s Hospital from Aug.2016 to Mar.2017 were included for the retrospective review.The CT data of the ureteral stones and the ureteral dilatation were collected, including the position of stone, the transverse and longitudinal diameter of stone, and the transverse diameter of dilated upper ureter and ureteropelvic junction (UPJ).The distribution of ureteral stones and dilatation in different parts of ureter were compared and analyzed.Results: All of the 129 cases of ureteral stone, stones were located at UPJ in 9 cases (7.0%), proximal ureter in 75 (58.0%), ureter crossing external iliac vessel (UEIV) in 6 (4.7%), distal ureter in 26 (20.2%), and ure-terovesical junction (UVJ) in 13 (10.1%).The mean transverse diameter of proximal ureteral stones was greater than that of distal ureteral stones [(8.47±2.36) mm vs.(6.74±1.99) mm, P<0.001], as the same as the mean longitudinal diameter [(11.00±4.41) mm vs.(7.50±4.28) mm, P<0.001].In 114 cases of dilated ureter for stone, the UPJ had a greater transverse diameter compared with the upper ureter [(14.39±6.09) mm vs.(11.45±3.85) mm, P<0.001].Conclusion: The most common location of stone is the proximal ureter in patients for endourologic lithotripsy, as the location in UEIV is rare.Both transverse and longitudinal diameters of stone in proximal ureter are greater than those in distal ureter.For dilated ureter, it is more severe in UPJ than in upper ureter.Traditionally, it is accepted that the stones lodge at 3 sites of natural narrowing in ureter, which may be questioned.

Objectives To identify and characterize 10 strains of Francisella philomiragia-like organisms isolated from blood samples and environmental water.Methods The 10 clinical and environmental isolates were identified by traditional morphological examination and biochemical characterization,matrix-assisted laser desorption/ionization time of flight(MALDI-TOF) mass spectrometry(MS) systems and sequencing based on 16S rRNA gene.The minimum inhibitory concentrations were tested by E-test methods.Results All the 10 isolates were gram-negative coccobacilli appearing tiny and faint counterstain of safranin,negative for urease,nitrate reduction and X and/or V factor requirement,but positive for oxidase and catalase.The isolates grew rapidly in sheep blood agar,chocolate agar and BCYE plate forming white opaque,colorless transparent or gray smooth colonies with about 2-mm diameters,but did not grow in M-H agar and MacConkey agar.The sequencing for 16S rRNA gene indicated that the 10 isolates shared more than 99.6％ similarity to Francisella philomiragia,and fell into the same clusters of Francisella philomiragia on phylogenetic tree.The MALDI-TOF MS analysis also showed the typical peaks with 6 153 m/z,5 180 m/z,7 757 m/z and 9 392 m/z which were similar to Francisella philomiragia ATCC 25015.However,they may be misidentified to be Sphingomonas paucimobilis by using Vitek 2 GN cards,Neisseria cinerea by using Vitek 2 NH cards,Myroides odoratimimus by using API 20NE strips and Haemophilus by using API NH cards.The results of antimicrobial susceptibility showed that they were all sensitive to chloramphenicol,doxycycline,tetracycline,gentamicin,ofloxacin and ciprofloxacin.Conclusion The 10 isolates could be identified as Francisella philomiragia,so we should pay more attention to the infrequent pathogen for its inactive biochemical reaction and the misidentification by commercial detection systems.

Objective: To evaluate the effects of percutaneous nephrolithotomy (PNL) in the treatment of medullary sponge kidney with calculi. Methods: A total of 77 patients (91 renal units) of medullary sponge kidney with calculi (MSK group) and 77 patients (77 renal units) with common kidney stone (control group) received PNL at Department of Urology in Peking University People′s Hospital from September 2006 to February 2016 were analyzed retrospectively. The MSK group included 33 males and 44 females with a mean age of (42.1±13.2) years, the mean stone burden was (3.9±1.8) cm. The control group included 36 males and 41 females with a mean age of (45.3±13.0) years, the mean stone burden was (3.6±1.5) cm. The numbers of tracts, the time of operation, the drop of hemoglobin, the change of creatine, the time of hospitalization, the stone free rate and major complications were compared between the two groups. The measurement data and numeration data were compared with t test and χ² test. Results: There were no significant differences in sex, age, preoperative urinary tract infection, stone type, and stone burden between the two groups (all P>0.05). The proportion of bilateral renal calculus in MSK group was higher (18.2% vs. 0, χ²=15.400, P=0.000). There were 159 percutaneous channels were established in MSK group while 90 percutaneous channels were established in control group. Compared with the control group, the operation time ((88.1±37.5) minutes vs. (68.5±30.1) minutes, t=3.543, P=0.000) and hospitalization time ((15.1±8.3) days vs. (10.1±3.6) days, t=4.816, P=0.000) were longer, the creatinine level increased ((101.2±62.6) μmol/L vs. (71.3±23.6) μmol/L, t=3.777, P=0.000), the rate of stone free decreased (27.5% vs. 83.1%, χ²=51.840, P=0.000) and the rate of complications increased (29.9% vs. 11.7%, χ²=8.114, P=0.004) in MSK group. There was no statistically difference in hemoglobin drop ((12.5±13.2) g/L vs. (13.0±10.9) g/L, t=-0.260, P=0.795). Conclusions Using PNL for patients of MSK with calculi has a lower stone free rate and a higher complications. It is an effective method for patients of MSK with large and complex calculi.

Objective To analyze the clinic-pathological data and peritubular capillary (PTC) injuries of malignant nephrosclerosis (MN) patients and their correlations with the long term renal survival.Methods This was a retrospective cohort study of 52 MN patients in Peking Union Medical College Hospital from January 2003 to March 2012.Their clinical data and renal biopsy samples were carefully studied.CD34 staining was performed to evaluate the PTC area,using Benign nephrosclerosis (BN,n=17) patients and glomerular minimal lesions (GML,n=19) patients as controls.Multivariate Cox proportional hazard model was used to identify the potential independent risk factors for long term renal survival.Results Fifty-two MN patients were enrolled.The sex ratio of male to female was 12:1 and the average age was (34.0±8.2) years.The maximum blood pressure (SBP/DBP) was (230.4 ± 25.0)/(156.4 ± 20.6) mmHg,companied with significant loss of eGFR and proteinuria.Glomerular sclerosis index,tubular atrophy and interstitial fibrosis correlated with eGFR and proteinuria (P ＜ 0.05).After aggressive treatment,BP control rate improved significantly (76.9％ vs 3.7％,P ＜0.01),Scr [(376.4±263.8) μmol/L vs (486.8±375.7) μmol/L,Wilcoxon test,P＜ 0.01] and proteinuria [(1.10±0.70) g/24 h vs (2.04± 1.26) g/24 h,P ＜ 0.01,n=21] also improved.PTC area in MN patients was significantly lower than those in BN patients and GML patients,and it correlated well with Scr (r=-0.553,P=0.001) and eGFR (r=0.476,P=0.004).The median follow-up time was 74 months,the cumulative renal survival rate at 1 year,5 year and 10 year was 90％,64％ and 23％,respectively.Kaplan-Meier analysis showed that the patients with higher PTC area had longer renal survival time [(114.8± 12.4) months vs (63.0±8.3) months, x2=5.312,P ＜ 0.05].Univariate Cox proportional hazard model found that unsatisfied BP control,eGFR ＜ 30 ml · min-1 · (1.73 m2)-1 upon discharge,lower PTC area,severer tubular-interstitial damage and anemia were associated with poor renal outcome.Multivariate Cox model showed that unsatisfied BP control (RR=3.89,95％ CI 1.75-8.65,P=0.001),eGFR ＜ 30 ml · min-1 · (1.73 m2)-1 upon discharge (RR=4.27,95％ CI 1.40-13.09,P=0.011) were independent risk factors for long-term renal survival.Conclusions The correlation between PTC area and renal functions in MN patients are much better than that of classic vascular changes.Unsatisfied BP control and eGFR ＜ 30 ml · min-1 · (1.73 m2)-1 upon discharge are independent risk factors for long-term renal survival.