Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.

Objective:To investigate the mechanism of trigger point deactivation induced by pressing manipulation in a rat model and to explore its potential regulation of the inflammatory response through the extracellular signal-regulated kinase(ERK)/nuclear factor-κB(NF-κB)pathway. Methods:Fifty male Sprague-Dawley rats were randomly divided into a blank group,a model group,a pressing manipulation group,an ERK agonist group,and a pressing manipulation+ERK agonist group,with 10 rats in each group.Except for the blank group,rats in other groups were used to establish the trigger point rat model using the blunt blow combined with the eccentric exercise method.The pressing manipulation group underwent pressing manipulation intervention at the trigger points.The ERK agonist group received an injection of recombinant human epidermal growth factor via the tail vein.The pressing manipulation+ERK agonist group received interventions from both the pressing manipulation and ERK agonist groups.The pressure pain threshold(PPT)was measured by a mechanical pain threshold detector before and after the intervention.The histological changes were evaluated by hematoxylin-eosin staining after the intervention;the expression levels of ERK,phosphorylated ERK(p-ERK),NF-κB p65(p65),phosphorylated NF-κB p65(p-p65),and phosphorylated NF-κB inhibitor(p-IκB)were detected by Western blotting;the levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay. Results:The PPT increased(P<0.05);the inflammatory cells disappeared;the ratios of p-ERK/ERK,p-p65/p65,and p-IκB/β-actin,also the levels of IL-1β,IL-6,and TNF-α all decreased in the pressing manipulation group after the intervention compared with the model group(P<0.05).The PPT decreased significantly(P<0.05),the inflammatory cell presence increased,and the ratios of p-ERK/ERK and p-p65/p65 were elevated(P<0.05);additionally,the levels of IL-6 and TNF-α were significantly higher in the pressing manipulation+ERK agonist group compared with the pressing manipulation group(P<0.05).The PPT was significantly lower(P<0.05),the inflammatory cell count was higher,the ratios of p-ERK/ERK and p-IκB/β-actin and the levels of IL-1β and TNF-α were significantly higher in the ERK agonist group compared with the pressing manipulation+ERK agonist group(P<0.05). Conclusion:Pressing manipulation can effectively alleviate inflammation and pain in trigger point model rats,potentially by inhibiting the ERK/NF-κB signaling pathway.

Objective: To explore the present situation and epidemiological characteristics of pesticide poisoning in Chengdu City from 2012 to 2021, and to provide scientific evidence for further prevention and control. Methods: In January 2022, the pesticide poisoning report cards of Chengdu City from 2012 to 2021 were collected from the China Disease Control and Prevention Information System. The data of the report card was reorganized and the distribution characteristics of pesticide poisoning such as time, region, gender, age and pesticide types were analyzed. Results: 14326 cases of pesticide poisoning were reported in Chengdu City from 2012 to 2021, 651 deaths, and the fatality rate was 4.54%. The cases of productive pesticide poisoning and unproductive pesticide poisoning were 504 and 13822, respectively. The fatality rates of productive and unproductive pesticide poisoning were 1.39% and 4.66%, which were significant different (χ(2)=11.99, P=0.001). The highest reported cases of pesticide poisoning was in 2013 (1779) and the lowest in 2021 (1047). The number of reported cases showed a downward trend year by year (t=-12.30, P<0.001), and the fatality rates also showed a downward trend year by year (χ(2)(trend)=25.48, P<0.001). The fluctuation range of unproductive pesticide poisoning cases in each month of the year was small, and the productive pesticide poisoning mainly occurred from May to August. The regions with the largest number of reported poisoning cases were Pengzhou (1620), Jianyang (1393), Jintang (1266) and Qionglai (1158). The high incidence of poisoning was among 25-54 years old (50.21%, 7193/14326). The fatality rate in the age group 75-96 years old was the highest (8.98%, 95/1058), and the fatality rates increased gradually with age (χ(2)(trend)=186.03, P<0.001). The pesticides causing poisoning were mainly insecticide (43.86%, 6284/14326) and herbicides (35.75%, 5121/14326). Herbicides paraquat had the highest fatality rate (9.54%, 286/2998) . Conclusion: Pesticide poisoning in Chengdu City is mainly unproductive poisoning. Health education should be carried out for key areas and people, and the control of highly toxic pesticides such as insecticide and herbicides should be strengthened.
Humans ; Aged ; Aged, 80 and over ; Adult ; Middle Aged ; Insecticides ; Pesticides ; Herbicides ; Paraquat ; Cities ; Poisoning/epidemiology*

Objective: To investigate the effect of root canal therapy (RCT) on inflammatory cytokines level in peripheral blood, anxiety, and depression in patients with pulpitis. Methods : A total of 155 patients with pulpitis admitted to the Stomatology Hospital of the Fourth Military Medical University from June 2021 to June 2022 were treated with root canal therapy. Another 155 persons who received health examinations during the same period were selected as the control group. The Generalized Anxiety Disorder-7 (GAD-7) scores and the Patient Health Questionnaire-9 (PHQ-9) scores of the two groups were compared. The GAD-7, PHQ-9 and pain scores of the test group before treatment and 3 and 6 weeks after treatment were compared. Pain was assessed with a visual analog scale (VAS). Inflammatory cytokine [interleukin-8 (IL-8), interleukin-1 β (IL-1β), tumor necrosis factor-α (TNF-α), c-reactive protein (CRP)] levels in the test group before treatment and 3 and 6 weeks after treatment were compared. Results : The GAD-7 and PHQ-9 scores in the test group were higher than those in the control group before treatment (P<0.05). The GAD-7 and PHQ-9 scores in the test group at 3 and 6 weeks after treatment were lower than those before treatment (P<0.05); there was no significant difference between the GAD-7 and PHQ-9 scores at 3 and 6 weeks after treatment(P>0.05). The pain scores of the experimental group at 3 and 6 weeks after treatment were lower than those before treatment (P<0.05), and the pain scores 6 weeks after treatment were lower than those at 3 weeks after treatment (P<0.05). The levels of IL-8, IL-1β, TNF-α and CRP in the peripheral blood of the experimental group were lower 3 and 6 weeks after treatment than before (P<0.05), and the levels of IL-8 and IL-1β in the peripheral blood at 6 weeks after treatment were significantly lower than at 3 weeks after treatment (P<0.05). The levels of TNF-α and CRP in the peripheral blood at 6 weeks after treatment were not significantly different from those at 3 weeks after treatment (P>0.05). Conclusion The peripheral blood of patients with pulpitis has a high level of inflammatory cytokines, and the patients suffer from obvious anxiety and depression. Root canal therapy can relieve their anxiety and depression by reducing their level of inflammatory cytokines in peripheral blood.

This study aims to explore the influence of Polygonati Rhizoma on the pyroptosis in the rat model of diabetic macroangiopathy via the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate specific proteinase-1(caspase-1)/gasdermin D(GSDMD) pathway. The rat model of diabetes was established by intraperitoneal injection of streptozotocin(STZ) combined with a high-fat, high-sugar diet. The blood glucose meter, fully automated biochemical analyzer, hematoxylin-eosin(HE) staining, enzyme-linked immunosorbent assay, immunofluorescence, immunohistochemistry, and Western blot were employed to measure blood glucose levels, lipid levels, vascular thickness, inflammatory cytokine levels, and expression levels of pyroptosis-related proteins. The mechanism of pharmacological interventions against the injury in the context of diabetes was thus explored. The results demonstrated the successful establishment of the model of diabetes. Compared with the control group, the model group showed elevated levels of fasting blood glucose, total cholesterol(TC), triglycerides(TG) and low-density lipoprotein cholesterol(LDL-c), lowered level of high-density lipoprotein cholesterol(HDL-c), thickened vascular intima, and elevated serum and aorta levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-18(IL-18). Moreover, the model group showed increased NLRP3 inflammasomes and up-regulated levels of caspase-1 and GSDMD in aortic vascular cells. Polygonati Rhizoma intervention reduced blood glucose and lipid levels, inhibited vascular thickening, lowered the levels of TNF-α, IL-1β, IL-18 in the serum and aorta, attenuated NLRP3 inflammasome expression, and down-regulated the expression levels of caspase-1 and GSDMD, compared with the model group. In summary, Polygonati Rhizoma can slow down the progression of diabetic macroangiopathy by inhibiting pyroptosis and alleviating local vascular inflammation.
Animals ; Rats ; Caspase 1/genetics* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Interleukin-18 ; Blood Glucose ; Pyroptosis ; Tumor Necrosis Factor-alpha ; Diabetes Complications ; Vascular Diseases ; Inflammasomes ; Cholesterol ; Lipids ; Diabetes Mellitus

Objective : To analyze the data related to the clinical outcome of preimplantation genetic testing (PGT) for double frozen , double biopsied blastocysts and double frozen , once biopsied blastocysts , in order to expand the existing data and provide some guidance for the clinical value and safety of PGT for frozen⁃thawed embryos . Methods : Retrospective analysis was made on the 38 PGT cycles of frozen⁃thawed blastocysts . According to the frequency of biopsy , cases in the study were divided into two groups : double frozen , double biopsy ( DFDB) group and double frozen , single biopsy ( DFSB) group . The freezing method was vitrification . Results : There were 24 patients in DFDB group , 34 blastocysts were not diagnosed in the last PGT cycle , 32 blastocysts survived after thawing , and the survival rate of thawed blastocysts was 94. 12% . After the second biopsy of these 32 blastocysts , genetic testing was performed , and all of them were definitely diagnosed , including 15 normal blastocysts (46. 88% ) and 17 abnormal blastocysts (53 . 13% ) . There were 14 patients in DFSB . The remaining 50 blastocysts in the last ICSI cycle were thawed and all blastocysts survived after thawing . Biopsy of these 50 blastocysts and genetic analysis showed that 47 blastocysts were diagnosed , including 9 normal blastocysts (18 . 00% ) , 28 abnormal blastocysts (56. 00% ) , 10 mosaic blastocysts (20. 00% ) , and 3 undiagnosed blastocysts (6. 00% ) . In DFDB group and DFSB group , 8 patients and 5 patients transferred the normal blastocystswhich all survivedafter thawing . There were 5 clinical pregnancies and 3 clinical pregnancies , respectively . One healthy live birth was obtained respectively in each group . Conclusion Acceptable pregnancy rate can be obtained whatever DFSB or DFDB blastocyst , which is of clinical value . However , due to the small sample size , we need to expand the sample size to further explore its safety .

Objective:To explore theepidemiological characteristics and analyse the survival of pneumoconiosis in Chengdu from 2011 to 2021, providing scientific evidence for further prevention and control.Methods:In April 2022, the pneumoconiosis report card of Chengdu from 2012 to 2021 and survival data were collected from the China Disease Control and prevention information system and the occupational pneumoconiosis follow-up survey project.The data of the report card was reorganized and analyzed by R4.4.0 software. Chi-square test was used to compare the case composition ratio between groups. The annual trend of the number of new pneumo coniosis cases was analyzed by linear regression model Kaplan-Meier method was used for survival analysis and log-rank test was used for comparison of survival curves between groups.Results:816 cases of pneumoconiosis were reported in Chengdu from 2011 to 2021, including 522 cases of stage Ⅰ (63.97%, 522/816), 148 cases of stage Ⅱ (18.14%, 148/816) and 146 cases of stage Ⅲ pneumoconiosis (17.89146/816) ; There were 596 cases of silicosis (73.04%, 596/816), 143 cases of coal worker's pneumoconiosis (17.52%, 143/816). New onset pneumoconiosis was mainly male (810 cases, 99.26%). The median age of diagnosis and the 25th and 75th percentile were 63 (51-71) years old, the median length of dust exposure were 12.00 (5.92-28.00) years, and the types of work were mainly rock drillers (24.63%, 201/816), tunneling workers (19.36%, 158/816) and coal miners (13.60%, 111/816). Among 816 cases of new pneumoconiosis, 35 cases were lost to follow-up (4.29%, 35/816), 605 cases survived and 176 cases died. The 5-year survival rate was 78.6% and the 10-year survival rate was 65.8%.Conclusion:The number of pneumoconiosis reported in Chengdu was relatively stable in recent years. The main type of pneumoconiosis was silicosis, which was concentrated in regions, industries and types of work. We should continue to strengthen the prevention and treatment of pneumoconiosis.

Objective:To explore theepidemiological characteristics and analyse the survival of pneumoconiosis in Chengdu from 2011 to 2021, providing scientific evidence for further prevention and control.Methods:In April 2022, the pneumoconiosis report card of Chengdu from 2012 to 2021 and survival data were collected from the China Disease Control and prevention information system and the occupational pneumoconiosis follow-up survey project.The data of the report card was reorganized and analyzed by R4.4.0 software. Chi-square test was used to compare the case composition ratio between groups. The annual trend of the number of new pneumo coniosis cases was analyzed by linear regression model Kaplan-Meier method was used for survival analysis and log-rank test was used for comparison of survival curves between groups.Results:816 cases of pneumoconiosis were reported in Chengdu from 2011 to 2021, including 522 cases of stage Ⅰ (63.97%, 522/816), 148 cases of stage Ⅱ (18.14%, 148/816) and 146 cases of stage Ⅲ pneumoconiosis (17.89146/816) ; There were 596 cases of silicosis (73.04%, 596/816), 143 cases of coal worker's pneumoconiosis (17.52%, 143/816). New onset pneumoconiosis was mainly male (810 cases, 99.26%). The median age of diagnosis and the 25th and 75th percentile were 63 (51-71) years old, the median length of dust exposure were 12.00 (5.92-28.00) years, and the types of work were mainly rock drillers (24.63%, 201/816), tunneling workers (19.36%, 158/816) and coal miners (13.60%, 111/816). Among 816 cases of new pneumoconiosis, 35 cases were lost to follow-up (4.29%, 35/816), 605 cases survived and 176 cases died. The 5-year survival rate was 78.6% and the 10-year survival rate was 65.8%.Conclusion:The number of pneumoconiosis reported in Chengdu was relatively stable in recent years. The main type of pneumoconiosis was silicosis, which was concentrated in regions, industries and types of work. We should continue to strengthen the prevention and treatment of pneumoconiosis.

Objective: To analyze the clinical characteristics of 6 children with TTC21B-related nephronophthisis to provide reference for early clinical diagnosis. Methods: The general condition, clinical manifestations, laboratory tests and other clinical data of 6 children from 4 families diagnosed with nephronophthisis by genetic testing in Shanghai Children's Hospital from January 2015 to December 2020 were analyzed retrospectively. Results: A total of 6 children (3 males and 3 females) developed proteinuria and progressive renal dysfunction in early infancy. The onset age of proteinuria was 18 (6, 25) months. The age at the onset of renal impairment was 22 (10, 36) months. All 6 children progressed to end-stage renal disease (ESRD) within 10 (4, 65) months of onset. Five children had hypertension, 3 children with abnormal liver function, 2 children with visceral translocation and 1 child with growth retardation. The genetic results suggested that all children carried variations TTC21B gene p.C518R. Conclusions: Children with TTC21B gene p.C518R nephronophthisis had proteinuria and progressed to ESRD at the early stage of life. These nephronophthisis patients commonly presented with liver and renal dysfunction.
China ; Female ; Humans ; Kidney Diseases, Cystic/genetics* ; Kidney Failure, Chronic/genetics* ; Male ; Phenotype ; Proteinuria/genetics* ; Retrospective Studies

Objective:To investigate the effects of single intermittent theta-burst stimulation on functional connectivity in patients with mild cognitive impairment(MCI).Methods:From July to November 2020, forty MCI patients were selected and randomly divided into iTBS true stimulation group and iTBS sham-stimulation group, with 20 patients in each group.iTBS targeted the left dorsolateral prefrontal cortex (DLPFC). Montreal cognitive assessment (MoCA), mini-mental state examination (MMSE), activity of daily living scale(ADL), Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) were evaluated at baseline.The resting state electroencephalography (rsEEG) was collected for 5 minutes before and after iTBS in the two groups.The phase lag index(PLI) of EEG functional connectivity was calculated, and the functional connectivity matrix diagram was drawn.SPSS 26.0 software was used for statistical analysis.Data were statistically analyzed by χ2 test, Wilcoxon rank sum test and independent sample t-test. Results:There were no significant differences in scores of MoCA, ADL, HAMD and HAMA between the two groups(all P>0.05). In the iTBS true stimulation group, compared with that before iTBS treatment(0.140(0.133, 0.144)), the PLI of β band increased significantly after iTBS treatment(0.146(0.136, 0.167))( P<0.05). The region of increased PLI was mainly concentrated in the central region(C3/C4-T7/T8). Compared with that before iTBS treatment(0.251(0.232, 0.299)), the PLI of α band increased after iTBS treatment(0.286(0.241, 0.359)), but the difference was not statistically significant( P>0.05). Conclusion:Single iTBS treatment can significantly increase the EEG functional connectivity in patients with MCI, indicating that iTBS targeting the left DLPFC can effectively regulate the EEG functional connectivity in patients with MCI, which may reveal the mechanism of iTBS in improving cognitive function in patients with MCI.