Objective To explore the effects of hypoxia on spermatid differentiation and stability of sperm flagellar microtubule,and investigate the underlying molecular mechanisms in order to clarify the potential adverse effects of hypoxia on male reproductive function.Methods Forty-eight 8-week-old healthy male SD rats(weighing 300～399 g)were subjected in this study.The experiments included ① an oxygen concentration gradient experiment(n=6):21％oxygen was regarded as normoxia(control),and 13.5％,11.8％,and 10.4％ oxygen were used to simulate hypoxic environments at altitudes of 3 500,4 500 and 5 500 m,respectively,for a continuous exposure of 2 months;② a time gradient experiment(n=6):the rats were exposed to 10.4％ oxygen for 0,0.5,1,and 2 months,respectively.Flow cytometry was employed to isolate round spermatids,and the following methods were employed to measure relevant indicators:① RNA sequencing to analyze gene expression profile changes related to impaired spermatogenesis and abnormal flagellar structure under hypoxic stress;②Western blotting to detect the expression levels of key proteins CEP290,RING 1A,and H2AK119ub;③ fluorescence recovery after photobleaching(FRAP)to monitor microtubule assembly dynamics and assess the immediate impact of hypoxia on microtubule stability.Results In the oxygen concentration gradient experiment,after 2 months of exposure to 10.4％ oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids in rat seminiferous tubules were significantly increased(P＜0.05),reaching 1.33±0.04,1.06±0.01 and 1.60±0.02 times higher,respectively than that of the 21％ normoxia group.Conversely,the proportions of primary spermatocytes and elongated spermatids were obviously decreased(P＜0.05),taking 0.89±0.01 and 0.88±0.000 2 times respectively when compared with that of the 21％ normoxia group,in a oxygen concentration-depended manner.In the time gradient experiment,after 0.5 months of exposure to 10.4％oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids began to increase(P＜0.05),reaching 1.11±0.03,1.04±0.01 and 1.29±0.003 times higher,respectively than that of the 0-month control group.The proportions of primary spermatocytes and elongated spermatids started to significantly decrease(P＜0.05)after 1 month of exposure,only 0.94±0.03 and 0.95±0.008 times,respectively than that of the 0-month control group.After 2 months of exposure to 10.4％ oxygen,the rate of sperm tail abnormalities in the epididymis of rats was significantly increased(P＜0.05),rising from(12.1±1.7)％ in the 21％ normoxia group to(30.8±3.7)％.In G2 spermatocytes exposed to 1％ hypoxia for 24 h,FRAP revealed a decrease in microtubule assembly rate and enhanced microtubule dynamic instability,with the maximum fluorescence recovery value decreasing from 0.37±0.02 in the normoxia group to 0.29±0.01.The results of RNA sequencing showed that under hypoxic condition,the transcription level of the key cilium basal body molecule CEP290 was increased,with an upregulation of 1.81±0.11 times than that of the 21％ normoxia group.In contrast,the expression levels of PRC1 complex members RING 1A,RING 1B,CBX2,PHC1,and PCGF1 were decreased,to 0.74±0.02,0.73±0.01,0.78±0.02,0.71±0.01 and 0.86±0.03 times of that of the 21％ normoxia group,respectively.Western blotting indicated that the protein level of CEP290 was up-regulated in the hypoxia group,while that of RING 1A was down-regulated.ChIP-qPCR experiments showed that the binding of RING 1A and its product H2AK119ub to the CEP290 promoter were significantly decreased(P＜0.000 1),with binding strengths of 0.38±0.02 and 0.52±0.06 times of that of the 21％ normoxia group,respectively.In siRING 1A-treated G2 cells,the binding of H2AK119ub to the CEP290 promoter was significantly decreased(P＜0.000 1),with a binding strength of 0.74±0.06 times of that of the control group,while CEP290 mRNA level was significantly increased(P＜0.000 1),with an up-regulation of 3.35±0.37 times.Conclusion Hypoxic environment impair sperm flagellar microtubule stability via the RING 1A-H2AK119ub-CEP290 signaling axis,which affects spermatid differentiation and leads to spermatogenic dysfunction.

OBJECTIVE To explore the mechanism of Shaoyao gancao decoction in improving intestinal motility in rats with slow transit constipation(STC)by regulating acid-sensitive ion channel 3(ASIC3)/extracellular signal-regulated kinase(ERK)signaling pathway.METHODS SD rats were used to construct an STC model by gavage with compound diphenoxylate.The successfully modeled rats were randomly divided into model group,Shaoyao gancao decoction group(1.5 g/mL),lactulose group(208.4 mg/mL,positive control),and combined inhibition group(Shaoyao gancao decoction 1.5 g/mL+amiloride hydrochloride 20 μg/kg),with 12 rats in each group.Additionally,12 healthy rats were selected as the blank group.They were given relevant medicine once a day and continuously intervened for 14 days.After intervention,the intestinal propulsion function and visceral sensitivity of the model rats were detected.The expression of ASIC3 in the colon tissue of rats was observed by immunohistochemical staining.mRNA expressions of ASIC3,ERK1 and ERK2 as well as protein expressions of ASIC3,ERK1/2 and phosphorylated ERK1/2(p-ERK1/2)in colon tissue of rats were detected;the ultrastructural changes of the enteric nervous system(ENS)-interstitial cell of Cajal(ICC)-smooth muscle cell(SMC)network in the rat colon were observed under electron microscopy.RESULTS Compared with the model group,the intestinal propulsion rate of the Shaoyao gancao decoction group was significantly increased,while the visceral pain threshold was significantly decreased.The proportion of the positive area of ASIC3 in the colonic tissue was significantly increased.The relative mRNA expression levels of ERK1,ERK2,and ASIC3,as well as the relative protein expression levels of p-ERK1/2 and ASIC3,and the p-ERK1/2 to ERK1/2 in the colonic tissue,were all significantly increased(P＜0.05 or P＜0.01).Additionally,there was marked repair of the morphological structure of ICC and SMC,with closer gap junctions observed.Compared with the Shaoyao gancao decoction group,the combined inhibition group exhibited a diminished improvement in intestinal motility of rats,with statistically significant differences in the levels of some indicators(P＜0.05 or P＜0.01);the repairing of the morphological structure of ICC and SMC was notably attenuated.CONCLUSIONS Shaoyao gancao decoction can effectively improve the intestinal transmission function and promote intestinal repair in STC rats,and its mechanism may be related to regulating the balance of the ENS-ICC-SMC network mediated by the ASIC3/ERK signaling pathway,thus promoting intestinal motility and reducing visceral sensitivity.

[Objective]To present Professor HE Ruoping's clinical experience in treating esophageal cancer.[Methods]Through the follow-up study,relevant medical cases were collected,organized and analyzed to describe the clinical experience of Professor HE Ruoping in the treatment of esophageal cancer in terms of the etiology and mechanism of the disease,and the rules and methods of treatment.A medical record was attached as evidence.[Results]Professor HE Ruoping believes that the pathogenic characteristic of esophageal cancer is a deficiency in origin and an enrichment in symptom.Deficiency in origin indicates weakness in Zang and Fu,while enrichment in symptom suggests there're Qi stagnation,phlegm,blood stasis and hot toxin."Strengthen healthy Qi,eliminate pathogens,and treat according to the symptoms"is the therapeutic approach used to treat esophageal cancer.The aim is to strengthen Zang and Fu,specifically the spleen,stomach and kidney.Treatments for anti-cancer mainly include moving Qi and dissipating mass,eliminating phlegm and removing blood stasis,clearing heat and toxin,etc.It emphasizes that the elimination of pathogenic factors should be carried out in an appropriate manner and should not hurt the body's positive Qi.Treating according to the symptoms means treating patients with various kinds of uncomfortable symptoms after surgery,radiotherapy and local stent placement to improve their quality of life.In the attached medical case,the above three principles were carried through the whole treatment process,and achieved good therapeutic effect.[Conclusion]By expounding the principle of"strengthen healthy Qi,eliminate pathogens and treat diseases according to the symptoms",it has summarized Professor HE Ruoping's clinical experience in the treatment of esophageal cancer,which is of some significance for the clinical treatment of this disease.

Objective:This study aimed to investigate the effect of short-term antipsychotic medication treatment of patients with schizophrenia on the effect of the thalamocortical resting-state functional connectivity.Methods:83 first-episode drug-na?ve schizophrenia patients and 117 matched healthy controls participated in the present study. The study collected resting-state fMRI data before and after the patients received short-term antipsychotics to assess the changes in the thalamocortical circuits and clinical symptoms. The directional interactions between the thalamus and other brain regions were investigated using a standard seed-based whole-brain correlation by choosing the bilateral thalamus as the seeds. Spearman′s correlation analysis was carried out between the change of abnormal functional connectivity and improved clinical symptoms in patients.Results:Compared with the healthy controls, schizophrenia patients showed decreased thalamic-prefrontal functional connectivity (including the middle frontal cortex, inferior frontal cortex, middle cingulate cortex, posterior cingulate cortex, and inferior parietal lobe, all P<0.05, FDR corrected) and increased thalamic-sensorimotor functional connectivity(including the precentral gyrus, superior temporal cortex, middle temporal cortex, inferior temporal cortex, parahippocampus, and middle occipital cortex, all P<0.05, FDR corrected)at baseline. After short-term antipsychotic treatment, the thalamic-prefrontal hypo-connectivity was significantly enhanced, and the thalamic-sensorimotor hyper-connectivity was significantly decreased. Furthermore, the changes of abnormal functional connectivity were correlated significantly with the PANSS total score changes improvement ( r=0.435, P=0.014; r=0.394, P=0.028,uncorrected). Conclusions:The present study replicates previous findings that the abnormalities of thalamocortical circuits in schizophrenia are characterized by thalamic-prefrontal hypoconnectivity and thalamic-sensorimotor hyperconnectivity. Moreover, short-term antipsychotic treatment partly improves thalamocortical abnormalities, which further relates to clinical symptom relief; Restoring of abnormal thalamocortical circuits plays an important role in the early treatment of schizophrenia.

Objective:This study aimed to investigate the effect of short-term antipsychotic medication treatment of patients with schizophrenia on the effect of the thalamocortical resting-state functional connectivity.Methods:83 first-episode drug-na?ve schizophrenia patients and 117 matched healthy controls participated in the present study. The study collected resting-state fMRI data before and after the patients received short-term antipsychotics to assess the changes in the thalamocortical circuits and clinical symptoms. The directional interactions between the thalamus and other brain regions were investigated using a standard seed-based whole-brain correlation by choosing the bilateral thalamus as the seeds. Spearman′s correlation analysis was carried out between the change of abnormal functional connectivity and improved clinical symptoms in patients.Results:Compared with the healthy controls, schizophrenia patients showed decreased thalamic-prefrontal functional connectivity (including the middle frontal cortex, inferior frontal cortex, middle cingulate cortex, posterior cingulate cortex, and inferior parietal lobe, all P<0.05, FDR corrected) and increased thalamic-sensorimotor functional connectivity(including the precentral gyrus, superior temporal cortex, middle temporal cortex, inferior temporal cortex, parahippocampus, and middle occipital cortex, all P<0.05, FDR corrected)at baseline. After short-term antipsychotic treatment, the thalamic-prefrontal hypo-connectivity was significantly enhanced, and the thalamic-sensorimotor hyper-connectivity was significantly decreased. Furthermore, the changes of abnormal functional connectivity were correlated significantly with the PANSS total score changes improvement ( r=0.435, P=0.014; r=0.394, P=0.028,uncorrected). Conclusions:The present study replicates previous findings that the abnormalities of thalamocortical circuits in schizophrenia are characterized by thalamic-prefrontal hypoconnectivity and thalamic-sensorimotor hyperconnectivity. Moreover, short-term antipsychotic treatment partly improves thalamocortical abnormalities, which further relates to clinical symptom relief; Restoring of abnormal thalamocortical circuits plays an important role in the early treatment of schizophrenia.

Objective To understand the comparability of the detection results of four items (ALT ,AST , GGT ,ALP) of liver enzymology in 11 clinical laboratories in Xinjiang Production and Construction Corps (XPCC) and offer reference for improving mutual recognition of the results .Methods Eleven clinical labora-tories of XPCC organized the result comparability tests of 4 items of liver enzymology twice in 2017 ,and the samples with 5 batches were completed in each comparability test .One set of detection system in each labora-tory was used as comparability system according to comparability scheme .The detection results were analyzed through Robust Z Score and the evaluation criterion was :|Z|≤2 "satisfied";2< |Z|<3"warning";|Z|≥3 "not satisfied".Results The detection results of all 10 batch samples in 4 clinical laboratories showed |Z|≤2 in 2 comparability tests .In the first comparability test ,the detection results of 5 batch samples for 4 items were |Z|≤2 in 5 laboratories .In the second comparability test ,the detection results of 5 batch samples for 4 i-tems were |Z|≤2 in 8 laboratories ,but the ALT results of 5 batch samples in 1 laboratory showed positive deviation(Z≥3)and the GGT results of 5 batch samples in the other laboratory showed negative deviation (Z≤ -3) .Conclusion The 11 clinical laboratories in XPCC should continuously improve quality management system and make sure that the mutual recognition of the detection results of 4 items of liver enzymology is effective .

Objective To investigate the clinical, pathological features and risk factors of hyperuricemia in children with IgA nephropathy (IgAN). Methods A retrospective study of 269 primary IgAN children diagnosed between January 1, 2006 to December 31, 2017 at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University, was performed in the hyperuricemia group (uric acid>350 μmol/L) and the normal uric acid group. The clinical and pathological characteristics were analyzed, and the risk factors of hyperuricemia were analyzed by using multivariate logistic regression analysis. Results There were 185 males and 84 females in the 269 IgAN children with age of (9.2 ± 3.1) years old, among whom there were 70 patients (26.0％) accompanied by hyperuricemia. Clinical indicators such as hypertension, urea nitrogen, serum creatinine, blood lipids, urinary protein in hyperuricemia group were higher than those in normal uric acid group (all P<0.05), while estimated glomerular filtration rate, serum total protein and albumin were less (all P<0.05). There were 58 patients (23.0％) and 12 patients (70.5％) associated with hyperuricemia among IgAN children with CKD 1-2 and CKD 3-5. The proportion of hyperuricemia in CKD stage 3-5 IgAN children was statistically higher than that in normal uric acid group (P<0.01). The hyperuricemia group had a higher proportion of Lee IV and V grade, and a lower proportion of the Lee III grade than the normal uric acid group (all P<0.05). According to the Oxford pathological classification score, there was no significant difference in total scores of renal lesions, glomerular score, and tubulointerstitial score between the two groups (all P>0.05). According to the Katafuchi semi-quantitative score, there was no significant difference in the total scores of renal lesions, glomeruli, and tubulointerstitial scores (all P>0.05), while the hyperuricemia group had higher renal vascular scores than the normal uric acid group (P<0.01). Multivariate logistic regression analysis showed that hypertension (OR=12.596, 95％CI 1.778-89.243, P=0.011), higher total cholesterol (OR=1.192, 95％CI 1.064-1.336, P=0.002), higher urea nitrogen (OR=1.273, 95％CI 1.104-1.468, P=0.001), proteinuria 3+(OR=1.875, 95％CI 1.309-2.684, P=0.001), proteinuria 4+(OR=1.627, 95％CI 1.241-2.134, P<0.001) and CKD stage 3 (OR=3.355, 95％CI 1.376-8.181, P=0.008) were the risk factors of hyperuricemia in children with IgAN. Conclusions Twenty-six percent IgAN children patients are accompanied by hyperuricemia, and their clinical parameters and pathological changes are more severe than those in normal uric acid group. Hypertension, higher total cholesterol, higher urea nitrogen, proteinuria 3+/4+and CKD stage 3 are the risk factors of hyperuricemia in children with IgAN.

Objective To understand the prevalence rate and related factors of chronic kidney disease (CKD) among elderly people aged more than 65 years old in the 66th regiment of the fourth division of A Crops in Xinjiang .Methods A total of 2 030 elderly people aged more than 65 years old in the 66th regiment of the fourth division of XPCC were distributed in 6 communities . Totally 334 permanent residents aged more than 65 years old were chosen from 2 communities by the stratified random sampling method .The renal injury indicators and related factors were detected .Results Among 329 residents with intact data ,after the age correction ,the prevalence rate of albuminuria ,hematuria and renal function decrease were 22 .2% ,14 .2% ,4 .9% ,respectively .The prevalence rate of CKD in this group was 32 .8% ,CKD stage 1―3 were dominated .The awareness rate was 15 .1% .The multiva‐riate Logistic regression analysis showed that gender and hypertension were independently associated with CKD .Conclusion The prevalence rate of CKD among elderly people aged over 65 years old in the 66th regiment of the fourth division of this Crops is high‐er .The related factors are gender and hypertension .

Objective To verify the clinical applicability of the published standard intervals of routine clinical chemistry (WS/T404 .1‐2012 ,WS/T404 .2‐2012) based on the health examination results of Han and Uygur populations in Urumqi .Methods This was a retrospective study .The results of serum TP ,ALB ,ALT ,AST ,ALP ,GGT from healthy examination individuals of Han and Uygur populations (from 2013 August to 2015 January) were collected and the healthy cases (age range:20 -79 years old) were chosen to calculate the 2 .5% and 97 .5% percentiles ,excluding the significant abnormal results according to the Medical Deciding Level 2 recommended by Staland .The percents of health cases not falling in the published standard interval were calculated to meet the judgment criterion of verification (<10% ) .Results The test of normality revealed that the Han and Uygur's results of all veri‐fied items were skewed distributions .The 2 .5% and 97 .5% percentiles of the results of two populations were as follows ,TP(Han 65 -81 g/L ;Uygur 64-81 g/L) ,ALB(Han 41-53 g/L ;Uygur 40-52 g/L) ,ALT(Han:male 9-51 U/L and female 7-42 U/L ;Uygur:male 9-53 U/L and female 6-43 U/L) ,AST(Han:male 14-42 U/L and female 12-37 U/L ,Uygur:male 12-42 U/L and female 12-38 U/L) ,ALP(Han:male 45-119 U/L ;Uygur:male 47-122 U/L) ,ALP(female 20-49 years old:Han 35-95 U/L and Uygur 40-104 U/L) ,ALP(female 50-79 years old:Han 43-131 U/L and Uygur 51-132 U/L) ,GGT(Han:male 11-71 U/L and female 8-54 U/L ;Uygur :male 11 -73 U/L and female 7 -55 U/L ) .The percents of AST results for Han's male , Uygur's male and Uygur's female not falling in the published standard reference interval were slightly over 10% ,but AST results o‐ver 10% were mainly under the lower limit of the published standard reference interval .The health case percents for the other veri‐fied items of Han and Uygur populations not falling in the published standard reference interval were under 10% .Conclusion The published standard reference intervals of routine clinical chemistry (WS/T404 .1‐2012 ,WS/T404 .2‐2012) are applicable in our la‐boratory for the detection of Han and Uygur population .

Objective To provide the objective evidence for reducing stat test turnaround time (TAT) reasonably through the comparative analysis of different intervals of stat test TAT between emergency department (ED) and intensive care unit (ICU ) . Methods Laboratory information system was used to collect data about blood cell analysis and biochemical profiles of department of emergency and ICU from 1st January to 31th March ,2014 ,then comparatively analyzing different intervals of stat test TAT be‐tween two departments .Results TAT outlier rates of stat CBC tests ordered by ED and ICU were 2 .4% and 15 .1% ,and that of stat biochemical profiles ordered by ED and ICU were 12 .3% and 24 .5% ,respectively .there were no significant differences in mean times between order‐to‐receipt of stat CBC tests and biochemical profiles ordered by ED and collection‐to‐receipt of stat CBC tests and biochemical profiles ordered by ICU [(11 .2 ± 4 .0) min vs .(11 .2 ± 4 .5) min ,P>0 .05 ;(13 .2 ± 14 .1)min vs .(13 .8 ± 9 .8) min ,P>0 .05] .ED had significantly shorter mean time of receipt‐to‐report than ICU for stat CBC tests and biochemical profile [(5 .8 ± 4 .4) min vs .(19 .3 ± 12 .5) min ,P<0 .01 ;(34 .4 ± 10 .9) min vs .(35 .5 ± 13 .2) min ,P>0 .01] .The TAT mean times of stat CBC tests and biochemical profiles ordered by ED were shorter than those ordered by ICU [(17 .0 ± 6 .2) min vs .(30 .5 ± 14 .9) min ,P<0 .01 ;(46 .9 ± 17 .2) min vs .(49 .3 ± 16 .5) min ,P<0 .01] .Conclusion The ED TATs for CBC tests and biochemical pro‐files are reasonably set ,and each interval of the ED TATs is well controlled .The ICU TATs for CBCs and biochemical profiles should be reset ,and the process of stat test for ICU should be optimized .