Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective:To investigate the distribution of CGG repeat numbers in the FMR1 gene among reproductive-age women in China, providing data reference for carrier screening and genetic counseling of Fragile X syndrome. Methods:This cross-sectional study recruited 16 610 reproductive-age women from 12 medical institutions between July 2022 and October 2023. Peripheral venous blood samples (3 mL) were collected, and genomic DNA was extracted. The number of CGG repeats in the FMR1 gene was determined using the triplet-primed polymerase chain reaction (TP-PCR) combined with capillary electrophoresis technology. Statistical analyses were performed to assess the prevalence and distribution of CGG repeat expansions. Results:Among 16 610 women of childbearing age, 5 684 (34.220%) women had the same number of CGG repeats in the two alleles of FMR1 gene, and 10 926 (65.780%) women had different numbers of repeats in the two alleles. Among the 33 220 FMR1 alleles in 16 610 women of reproductive age, the most common CGG repeat numbers were 29 [48.645% (16 160/33 220)] and 30 [26.276% (8 729/33 220)], while the most frequent CGG genotype was CGG 29/29 [24.726% (4 107/16 610)]. The CGG repeat numbers of FMR1 gene were normal in 16 498 women (99.326%). Among the 112 women (0.674%) with CGG repeat abnormities, 96 (0.578%) women were classified as intermediate carriers, 15 (0.090%) as premutation carriers, and 1 (0.006%) as a full mutation carrier, whose CGG genotype was (36, >200). Conclusion:In the general reproductive-age female population in China, the normal CGG repeat numbers of the FMR1 gene account for 99.326%, while the intermediate carrier rate is 0.578%, and the combined carrier rate of the premutation and full mutation types is 0.096%.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

ObjectiveTo observe the intervention effect of Chaihu and Longgu Mulitang （CLMT） on rat depression model prepared by chronic unpredictable mild stress （CUMS） based on cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/cAMP-response element-binding protein （CREB）-brain-derived neurotrophic factor （BDNF） signaling pathway. MethodSixty SD rats were divided into normal group， model group， and CLMT low-， medium- and high-dose groups and fluoxetine group （positive control） according to random number table. They， except the normal group， were treated with CUMS for 49 days to prepare the rat depression model. The CLMT low-， medium- and high-dose groups were given 2.89， 5.78 11.56 g·kg^-1 of CHMD granules， respectively， and the fluoxetine group was given 2.06 mg·kg^-1 of fluoxetine hydrochloride on the 29^th day. The normal group and the model group received equal volume of normal saline for 21 days. The behavioral performance of rats were observed by open field test and forced swim test. The levels of 5-hydroxytryptamine （5-HT）， norepinephrine （NE） and cAMP in rat hippocampus were measured by enzyme-linked immunosorbent assay （ELISA）. The mRNA expressions of PKA， CREB， and BDNF in rat hippocampus were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the protein expressions of PKA and BDNF were detected by Western blot. Immunohistochemistry was used to determine the expression of CREB， and hematoxylin and eosin （HE） staining and Nissl staining were used to observe the morphological changes of hippocampus. ResultCompared with the conditions in the normal group， the immobility time of the model group in the forced swim test was increased （P<0.01） and the total movement distance， residence time in central area， number of entries in central area and movement distance in central area were decreased （P<0.01）. Additionally， the contents of 5-HT， NE and cAMP in hippocampus of the model group as well as the protein expressions of PKA， BDNF and CRE，the mRNA expressions of BDNF and CREB were lower than those in the normal group （P<0.01）. Compared with the model group， the CLMT groups had reduced immobility time （P<0.01）， elevated total movement distance， residence time in central area， number of entries in central area and movement distance in central area （P<0.05， P<0.01）， up-regulated contents of 5-HT， NE and cAMP in hippocampus （P<0.05， P<0.01）， and up-regulated protein expressions of PKA， BDNF and CREB and mRNA expressions of BDNF and CREB （P<0.01）. HE staining and Nissl staining showed that CLMT significantly improved the neuronal structure in rat hippocampus. ConclusionCLMT alleviates the anxiety and depression of rats. These effects may be mediated by regulating monoamine neurotransmitters 5-HT and NE in hippocampus of depressed rats， activating cAMP/PKA/CREB/BDNF signaling pathway， up-regulating the expression of BDNF and protecting hippocampal structure and function .

【Objective】 To investigate the expression of BMP8A in papillary thyroid carcinoma (PTC) and the relationship between its expression level and clinicopathological features of PTC patients. 【Methods】 Based on TCGA and GEO databases, we analyzed and screened BMP8A, one differentially expressed gene related to PTC. From April 2019 to October 2019, 35 cases of thyroid papillary carcinoma and the tumor-adjacent tissues were collected from the Department of Gastrointestinal Gland Surgery, the First Affiliated Hospital of Guangxi Medical University. Real-time PCR was used to detect the expression of BMP8A in PTC and tumor-adjacent tissues, and the relationship between different expression levels and clinicopathological features of the patients was analyzed and compared. Then, we used Western blotting for verification. 【Results】 Both Real-time PCR and Western blotting analyses proved that the expression of BMP8A in PTC was significantly lower than that in the tumor-adjacent tissues (P<0.05), and the expression of BMP8A was also significantly decreased in PTC tissues with cervical lymph node metastasis compared with those without metastasis(P<0.05). 【Conclusion】 BMP8A has a low expression in papillary thyroid carcinoma, and its expression level is related to cervical lymph node metastasis. BMP8A may be a suppressor gene of PTC. This may provide a new direction for further exploring the mechanism of cervical lymph node metastasis in PTC and preventing recurrence after surgery.

We introduce the background of Shanghai medical purchasing service and supervision platform (later we call it "open platform") and the effect of its implementation. We also analyze the problems occurred by medical institutions in the management of supplies, explore how to use open platform to strengthen the management of medical supplies, further optimize the structure of supplies, standardize the clinical reasonable use and charges, and ensure the quality, safety and traceability of supplies.
China ; Equipment and Supplies

Objective To observe the effects of total enteral nutrition ( TEN) and early combined parenteral nutrition ( PEN+TEN) in patients with esophageal cancer after operation .Methods The prospective,random, controlled clinical trial was adopted.One hundred patients receiving esophageal cancer operation were randomly assigned to the TEN group (50 cases) and the PEN+TEN group(50 cases).The differences in nutritional status, inflammatory response, immune status and postop-erative complications were compared in the two groups before and after operation.Results The levels of total serum protein, albumin or retinol binding protein were higher in the PEN group than the TEN group at the 10th day after operation, respective-ly[(60.1 ±6.2)g/L vs(55.3 ±9.3)g/L,(36.4 ±4.2)g/L vs(34.6 ±1.6)g/L,(43.3 ±5.9)g/L vs(34.9 ±3.3)g/L, P<0.05] .The levels of ESR or CRP were higher in PEN +TEN group than the TEN group at the 10th day after operation, re-spectively [(54.9 ±25.8)mm/h vs(31.8 ±14.2)mm/h,(30.9 ±13.2)g/L vs(15.8 ±6.1)g/L, P<0.01] .The levels of CD3+, CD4 +, or CD8 +were higher at the 10 th day after operation than at the day before surgery in TEN group [(59.6 ±9.8)％vs(68.3 ±4.4)％,(41.7 ±7.8)％vs(46.5 ±5.5)％,(23.2 ±5.5)％vs(20.0 ±2.7)％, P<0.05], but not in PEN+TEN group.The levels of IgA or IgG were significant higher in the TEN group than the PEN +TEN group at the 10th day after operation[(1.9 ±0.5)g/L vs(1.6 ±0.3)g/L,(11.9 ±3.3)g/L vs(9.4 ±2.2)g/L, P<0.01].Con-clusion The inflammatory reaction and immune function in TEN group are better than those in PEN +TEN group.Although the nutritional status is worse in the TEN group than that in the PEN group , but the rate of postoperative complications has not increased.

OBJECTIVETo investigate the associated high risk factors of postoperative relapse and metastasis for patients with confined tumors (grade pT1b-4a) without lymph-node metastases (pN0) in thoracic esophageal squamous cell carcinoma (ESCC).

METHODSClinicopathological and follow up data of ESCC patients undergoing radical surgical resection as primary treatment in the Department of Thoracic Surgery, Shanghai Chest Hospital between January 2004 and December 2012 from Hospital Database were retrospectively collected. The inclusion criteria were as follows: (1) the first development of ESCC confirmed by histopathology without lymphatic and distant metastasis; (2) pathological stage of pT1bN0M0 to pT4aN0M0 according to the Union for International Cancer Control (UICC) in 2009; (3) curative trans-thoracic esophagectomy with R0 (tumor-free surgical margin) resection, using the Ivor-Lewis or McKeown procedure; two-field lymphadenectomy or three-field lymph node dissection based on the positive results of preoperative cervical ultrasonography examination or CT scan; (4) without adjuvant chemotherapy and/or radiotherapy before and after operation; (5) complete follow-up data. Logistic regression analysis was employed to identify the clinicopathological factors affecting the postoperative relapse and metastasis.

RESULTSA total of 112 patients were eligible, including 94 male cases and 18 female cases; age of (58.6±7.7) years; squamous carcinoma of upper thorax in 25 cases, of middle thorax in 67 cases and of lower thorax segment in 20 cases; 12 cases of high-differentiated ESCC, 49 cases of moderate-differentiated ESCC, poorly-differentiated ESCC in 48 cases; 4 cases of I(a stage, 9 cases of I(b, 24 cases of II(a, 62 cases of II(b, 13 cases of III(a; the tumor length >4 cm in 43 cases, ≤4 cm in 69 cases. Forty-three (38.4%) patients presented relapse or metastasis during the follow-up, including 24 (21.4%) of loco-regional relapse, 13 (11.6%) of distant metastasis, and 6(5.4%) of both above. Multivariate regression analysis revealed that poorly-differentiated tumor (OR=1.899, 95%CI:1.233-2.925, P=0.004), upper-middle location (OR=2.351, 95%CI:1.188-4.653, P=0.014), and tumor length >4 cm (OR=2.381, 95%CI:1.009-5.618, P=0.048) were independent risk factors of overall postoperative relapse and metastasis for thoracic ESCC with stage pT1b N0M0-T4aN0M0. Further stratified analysis identified that only poorly-differentiated tumor (OR=1.730, 95%CI:1.121-2.671, P=0.013) was an independent risk factor of loco-regional relapse, whereas pathological stage II(b-III(a (OR=3.372, 95%CI:1.206-9.428, P=0.021) was an independent risk factor of distant metastasis.

CONCLUSIONSPoorly-differentiated tumor, tumor length >4 cm, and upper-middle location may be regarded as high risk factors for predicting overall relapse and metastasis of pN0 thoracic ESCC patients after esophagectomy. Moreover, poorly-differentiated tumor is the only independent risk factor of postoperative loco-regional relapse, meanwhile it should be noted that pathological stage II(b-III(a is closely related to postoperative distant metastasis.

Despite the complex vascular effects of dexmedetomidine (DEX), its actions on human pulmonary resistance arteries remain unknown. The present study tested the hypothesis that DEX inhibits vascular tension in human pulmonary arteries through the endothelial nitric oxide synthase (eNOS) mediated production of nitric oxide (NO). Pulmonary artery segments were obtained from 62 patients who underwent lung resection. The direct effects of DEX on human pulmonary artery tension and changes in vascular tension were determined by isometric force measurements recorded on a myograph. Arterial contractions caused by increasing concentrations of serotonin with DEX in the presence or absence of L-NAME (endothelial nitric oxide synthase inhibitor), yohimbine (α2-adrenoceptor antagonist) and indomethacin (cyclooxygenase inhibitor) as antagonists were also measured. DEX had no effect on endothelium-intact pulmonary arteries, whereas at concentrations of 10⁻⁸~10⁻⁶ mol/L, it elicited contractions in endothelium-denuded pulmonary arteries. DEX (0.3, 1, or 3×10⁻⁹ mmol/L) inhibited serotonin-induced contraction in arteries with intact endothelium in a dose-dependent manner. L-NAME and yohimbine abolished DEX-induced inhibition, whereas indomethacin had no effect. No inhibitory effect was observed in endothelium-denuded pulmonary arteries. DEX-induced inhibition of vasoconstriction in human pulmonary arteries is mediated by NO production induced by the activation of endothelial α₂-adrenoceptor and nitric oxide synthase.
Arteries ; Dexmedetomidine* ; Endothelium ; Humans ; Indomethacin ; Lung ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Nitric Oxide Synthase Type III* ; Pulmonary Artery ; Serotonin ; Vasoconstriction* ; Yohimbine