Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review

SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.

LC-MS analysis of 2-(2-phenylethyl) chromones in sodium chloride-treated suspension cells of Aquilaria sinensis / 中国中药杂志

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 μm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.

Synergistic effect of β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli in vitro / 生物工程学报

The widespread of tigecycline resistance gene tet(X4) has a serious impact on the clinical efficacy of tigecycline. The development of effective antibiotic adjuvants to combat the looming tigecycline resistance is needed. The synergistic activity between the natural compound β-thujaplicin and tigecycline in vitro was determined by the checkerboard broth microdilution assay and time-dependent killing curve. The mechanism underlining the synergistic effect between β-thujaplicin and tigecycline against tet(X4)-positive Escherichia coli was investigated by determining cell membrane permeability, bacterial intracellular reactive oxygen species (ROS) content, iron content, and tigecycline content. β-thujaplicin exhibited potentiation effect on tigecycline against tet(X4)-positive E. coli in vitro, and presented no significant hemolysis and cytotoxicity within the range of antibacterial concentrations. Mechanistic studies demonstrated that β-thujaplicin significantly increased the permeability of bacterial cell membranes, chelated bacterial intracellular iron, disrupted the iron homeostasis and significantly increased intracellular ROS level. The synergistic effect of β-thujaplicin and tigecycline was identified to be related to interfere with bacterial iron metabolism and facilitate bacterial cell membrane permeability. Our studies provided theoretical and practical data for the application of combined β-thujaplicin with tigecycline in the treatment of tet(X4)-positive E. coli infection.

Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy / 中华肿瘤杂志

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

Effects of tumor-treating field arrays on the radiation position and dose of glioblastoma / 中华放射医学与防护杂志

Objective:To preliminarily investigate the effects of tumor treating field (TTF) arrays on the positioning accuracy of radiotherapy setup in the treatment of glioblastoma.Methods:The kilovolt cone-beam CT (CBCT) and an X-ray volumetric imaging (XVI) system were used to verify the radiotherapy setup of 29 patients treated with conventional radiotherapy and 12 patients treated with TTF concurrent radiotherapy, respectively. The errors of radiotherapy position isocenter and treatment plan isocenter were evaluated in six directions, namely lateral (Lat), head pin (Lng), dorsoventral (Vrt), roll, pitch, and rotation (Rtn). Then, the plan isocenter was redetermined according to the setup error data. Moreover, the dose distribution was recalculated without changing the radiation field parameters. Finally, the V40, Dmean, D98% and D2% of both PTV and CTV and the Dmean, D20 cm 3, and D30 cm 3 of scalp tissue were evaluated. Results:When patients were treated with TTF concurrent radiotherapy wearing TTF arrays, the setup errors increased by 2 mm and 1.3 mm on average (maximum: 3.5 mm and 2.7 mm) toward the foot and dorsal directions, respectively. In addition, the setup errors in both Roll and Rtn directions increased by about 1.1° toward one side. The V40 and D98% of PTV decreased by up to 4.78% and 6%, respectively. The Dmean, D20 cm 3, and D30 cm 3 to scalp tissue increased by up to 2.6%, 3.2%, and 3.5%, respectively. The errors of other dose parameters for both CTV and PTV were within 2%. Conclusions:TTF arrays have significant effects on the setup errors of patients in the Lng and Vrt directions and increase the setup difficulty in the Roll and Rtn directions, while there is no significant error in the Lat and Pitch directions. Moreover, too large setup errors can significantly reduce the dose to PTV.

Analysis of expression of m 6A regulators in colorectal tumor samples based on TCGA and GEO databases / 中国基层医药

Objective:To detect the expression of N6-methyladenosine (m 6A) regulators in colorectal tumor samples and its clinical significance. Methods:From September to December 2021, the data regarding the expression of m 6A regulators in colorectal tumor samples were collected using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and the expression of m 6A regulators was compared between different clinical pathological characteristics and between different molecular subtypes. Survival analysis was conducted in patients with colorectal cancer with different m 6A expression levels. Results:In TCGA, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), and YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) were higher in colorectal tumor samples than normal tissue samples (TCGA-COAD: IGF2BP3: 12.80 vs. 204.46, logFC = 4.00, P = 0.003; YTHDF1: 2 347.56 vs. 3712.77, logFC = 0.66, P < 0.001; TCGA-READ: IGF2BP1: 6.20 vs. 359.32, logFC = 5.82, P = 0.007; YTHDF1: 2 470.10 vs. 4 369.09, logFC = 0.82, P = 0.020). The intersection of TCGA and GEO databases showed that methyltransferase like 14 (METTL14), YTH domain m 6A RNA binding protein 3 (YTHDF3), and α-ketoglutarate dependent dioxygenase AlkB homolog 5 (ALKBH5) were downregulated in colorectal tumor samples compared with normal tissue samples (TCGA-COAD: METTL14: 1 051.56 vs. 711.40, logFC = -0.56, P < 0.001; YTHDF3:4 613.85 vs. 3 155.05, logFC = -0.55, P < 0.001, ALKBH5: 4 250.10 vs. 2 555.55, logFC = -0.73, P < 0.001; TCGA-READ vs. METTL14: 1 113.3 vs. 674.36, logFC = -0.72, P < 0.001; YTHDF3: 5 034.30 vs. 3 331.95, logFC = -0.60, P = 0.004; ALKBH5: 4 902.20 vs. 2 529.71, logFC = -0.95, P < 0.001; GEO-CRC vs. METTL14: 6.58 vs. 6.33, logFC = -0.06, P < 0.001; YTHDF3: 6.28 vs. 6.20, logFC = -0.02, P = 0.002; ALKBH5: 5.07 vs. 4.98, logFC = -0.02, P < 0.001). In colorectal tumor samples of different molecular subtypes, IGF2BP2, HNRNPC, TP53 and YTHDF2 expression was low in KRAS (IGF2BP2: 48.53 vs. 44.04, t = 2.64, P = 0.008; HNRNPC: 121.30 vs. 112.60, t = 2.32, P = 0.020; TP53: 65.30 vs. 60.26, t = 2.11, P = 0.034; YTHDF2: 54.07 vs. 51.19; t = 1.97, P = 0.048). Different clinical pathological characteristics showed that IGF2BP1 was higher in colorectal cancer with positive lymph nodes (8.97 vs. 6.11, W = 20 008, P = 0.002), distant metastasis (8.94 vs. 6.41, W = 19 104, P = 0.009), or stage Ⅲ-Ⅳ (7.46 vs. 7.13, W = 8 779, P = 0.025) than normal tissue. ALKBH5 overexpression, advanced age, presence of vascular invasion, and late pathological staging were significantly related to a short survival period (high ALKBH5 expression vs. low ALKBH5 expression: 5.85 years vs. not available, HR: 1.63, 95% CI: 1.071-2.491, P = 0.021; > 68 years vs. < 68 years: 6.78 years vs. not available, HR: 1.59, 95% CI: 1.049-2.422, P = 0.047; stage Ⅲ-Ⅳ vs. stage Ⅰ-Ⅱ: 4.55 years vs. 8.33 years, HR: 2.89, 95% CI: 1.895-4.425, P < 0.001; presence of vein invasion vs. absence of vein invasion: 5.48 years vs. not available, HR: 2.82, 95% CI: 1.672-4.783, P < 0.001). Conclusion:Some of the m 6A regulators are associated with the biological characteristics and prognosis of colorectal cancer.

Survey results of drinking water iodine level in some areas of Jiangsu Province in 2020 / 中华地方病学杂志

Objective:To dynamically observe the changes in iodine level in residents' drinking water after the change of regional water supply mode (2020) in Jiangsu Province.Methods:The survey of water iodine level was conducted from June to October 2020 in administrative villages of Jiangsu Province with a median water iodine ≥40 μg/L in 2017. The survey mainly covered 1 537 administrative villages in 21 counties (cities and districts) of 5 cities, including Huaian City, Lianyungang City, Suqian City, Yancheng City, and Xuzhou City. Based on the standard of "Definition and Demarcation of Iodine Deficient Areas and Iodine Adequate Areas" (WS/T 669-2020), the administrative villages with a median water iodine of 40 - 100 μg/L were classified as iodine adequate areas. Water iodine testing was conducted using the "Method for Water Iodine Testing in Iodine Deficient and High Iodine Areas" recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:Totally 1 498 administrative villages in Jiangsu Province were monitored in 2020, all of which had centralized water supply. The minimum value of water iodine in all administrative villages was 1.2 μg/L and the maximum value was 606.7 μg/L, and the median water iodine was 35.2 μg/L. Among them, 206 administrative villages had median water iodine < 10 μg/L, accounting for 13.75% (206/1 498); 610 administrative villages had median water iodine from 10 to < 40 μg/L, accounting for 40.72% (610/1 498); 635 administrative villages had median water iodine from 40 to 100 μg/L, accounting for 42.39% (635/1 498); and 47 administrative villages with median water iodine > 100 μg/L, accounting for 3.14% (47/1 498). Except for Sucheng District in Suqian City, Xinyi City and Gulou District in Xuzhou City, Qingjiangpu District and Xuyi County in Huaian City, and Guannan County in Lianyungang City, the median water iodine in the administrative villages of the remaining 15 counties (cities and districts) in 2020 decreased significantly compared to 2017, and the differences were statistically significant ( P < 0.05). Conclusion:After change of regional water supply mode in 2020, in most monitored counties (cities and districts) of Jiangsu Province, the water iodine level of administrative villages has decreased significantly compared to 2017.

Analysis of surveillance results of drinking water-borne endemic fluorosis in Jiangsu Province in 2021 / 中华地方病学杂志

Objective:To learn about the implementation of prevention and control measures in drinking water-borne endemic fluorosis areas and the trend of the disease change in Jiangsu Province.Methods:In March to October 2021, a general survey was carried out in 1 972 villages with drinking water-borne endemic fluorosis in 27 counties (cities and districts) of Jiangsu Province, the operation of water improvement projects in the villages was monitored, and the water fluoride content was determined. The prevalence of dental fluorosis among children aged 8 to 12 years in all the villages was investigated.Results:The 1 972 villages with drinking water-borne endemic fluorosis had completed water improvement, and all water improvement projects were operating normally and the water was qualified. Among them, 1 774 villages in the disease affected areas had achieved the control goal, accounting for 89.96%; and there were 198 villages in the disease affected areas with control measures up to the standard, accounting for 10.04%. A total of 47 water improvement projects were monitored, including 2 small-scale water improvement projects, accounting for 4.26%. There were 45 large-scale water improvement projects, accounting for 95.74%. A total of 125 790 children aged 8 to 12 years were examined, and 12 625 cases of dental fluorosis were detected. The detection rate of dental fluorosis was 10.04%, and the dental fluorosis index was 0.19. The detection rate of dental fluorosis in children aged 8 to 12 years was 9.98% (1 854/18 579), 10.27% (2 704/26 323), 9.48% (2 765/29 152), 9.73% (2 835/29 145) and 10.92% (2 467/22 591), respectively, with statistically significant difference (χ 2 = 10.51, P = 0.015). Among the 198 villages with control measures up to standard, according to the historical water fluoride, the detection rate of dental fluorosis in children in each water fluoride range (1.20-2.00, 2.01-3.00, 3.01-4.00, > 4.00 mg/L) was 37.73% (698/1 850), 43.17% (1 176/2 724), 45.50% (769/1 690) and 55.20% (802/1 453), respectively, with a statistically significant difference (χ 2 = 104.15, P < 0.001). Conclusion:The water improvement measures in drinking water-borne endemic fluorosis areas in Jiangsu Province have achieved significant results, which still need to be further consolidated.

Analysis of influencing factors of dental fluorosis in children based on logistic regression and classification tree model / 中华地方病学杂志

Objective:To analyze the influencing factors of dental fluorosis of children in the drinking-water-borne endemic fluorosis (referred to as drinking-water-borne fluorosis) areas with qualified drinking water.Methods:In 2020 and 2021, the cluster sampling method was used to select the children aged 8 to 12 years old from the drinking-water-borne fluorisis areas with qualified drinking water in Tianjin City for water and urine fluoride detection, dental fluorosis examination and questionnaire survey, and logistic regression and classification tree model were used to analyze the influencing factors of dental fluorosis in children.Results:A total of 3 795 cases children aged 8 to 12 years old were investigated, and 1 001 cases of dental fluorosis were detected, and the detection rate of dental fluorosis was 26.38% (1 001/3 795). The results of logistic analysis showed that age [odds ratio ( OR) = 1.193, 95% confidence interval ( CI): 1.115 - 1.277], high urinary fluoride (1.84 - 19.40 mg/L, OR = 1.510, 95% CI: 1.169 - 1.952) and the number of permanent residents at home ≥6 ( OR = 1.377, 95% CI: 1.090 - 1.739) were risk factors of dental fluorosis in children; and the mother's with higher education level (college degree or above, OR = 0.664, 95% CI: 0.441 - 0.999), the years of water improvement ≥5 years (5 - < 10 years, OR = 0.193, 95% CI: 0.157 - 0.238; ≥10 years, OR = 0.254, 95% CI: 0.193 - 0.333) were protective factors of dental fluorosis in children. The results of classification tree model analysis showed that the years of water improvement contributed the most to the prevalence of dental fluorosis among children in the drinking-water-borne fluorisis areas with qualified drinking water, followed by age, number of permanent residents at home and urinary fluoride. The area under the receiver operating characteristic curve (AUC) of logistic regression model and classification tree model were 0.730 (95% CI: 0.711 - 0.748) and 0.721 (95% CI: 0.702 - 0.739), respectively, with good fitting effect. Conclusion:The detection rate of children's dental fluorosis in the drinking-water-borne fluorosis areas with qualified drinking water is mainly related to the years of water improvement, age, the number of permanent residents at home and urinary fluoride.

Microvascular perfusion characteristics of breast cancer by contrast-enhanced ultrasound and its comparison with pathology / 中国医师进修杂志

Objective:To study the characteristics of tumor microvascular perfusion by contrast-enhanced ultrasound (CEUS) in patients with breast cancer, and to analyze its relationship with pathology.Methods:The clinical data of 180 breast cancer patients admitted to Tangshan People′s Hospital from February 2019 to March 2021 were retrospectively analyzed. They were examined by contrast-enhanced ultrasound before surgery, and the specimens were sent for pathological biopsy after surgery. The characteristics of tumor microvascular perfusion under CEUS were observed, and the correlation between the characteristics and pathological classification and grade were analyzed.Results:The results of the CEUS showed that the contrast agentrapid infusion was 47.78%(86/180), slowly filled was 60.00%(108/180), the mass showed hyperenhancement when the contrast agent reached its peak was 42.78%(77/180), the contrast agent slowly withdrew was 42.78% (77/180), and the contrast agent retention in clearance was 65.56% (118/180). Pathological biopsy revealed that among 180 patients, 16 patients (8.89%) were non-invasive carcinoma, 41 patients (22.78%) were invasive lobular carcinoma, 88 patients (48.89%) were invasive ductal carcinoma, 10 patients (5.56%) were mucinous adenocarcinoma, 11 patients (6.11%) were medullary carcinoma, 8 patients (4.44%) were squamous carcinoma, 6 patients (3.33%) were hard carcinoma (3.33%). There was no correlation between tumor microvascular perfusion characteristics and pathological classification under CEUS ( P>0.05). Pathological biopsy showed that 95 patients (52.78%) were grade Ⅰ, 49 patients (27.22%) were gradeⅡand 36 patients (20.00%) were grad Ⅲ. There was a certain correlation between tumor microvascular perfusion characteristics and pathological grade under CEUS ( P<0.05). Conclusions:There is a certain relationship between tumor microvascular perfusion characteristics detected by CEUS and pathological grading in patients with breast cancer. Analysis of the microvascular perfusion characteristics can provide an important basis for pathological grading.

Efficacy of pelvic floor magnetic and electrical stimulation combined with Kegel exercise training in the treatment of stress urinary incontinence after minimally invasive surgery for benign prostatic hyperplasia / 现代泌尿外科杂志

【Objective】 To explore the clinical efficacy and safety of pelvic floor magnetic and electrical stimulation combined with Kegel exercise training in the treatment of stress urinary incontinence (SUI) after minimally invasive surgery for benign prostatic hyperplasia (BPH). 【Methods】 A total of 52 patients with SUI after minimally invasive surgery for BPH treated during Jan.2016 and Feb.2022 were randomly divided into test group (n=26) and control group (n=26). The test group received pelvic floor magnetic and electrical stimulation and Kegel exercise training, while the control group received Kegel exercise training only. The treatment lasted for 3 months. The scores of International Consultation on Incontinence Modular Questionnaire Short Form (ICIQ-SF), 1 h pad test, International Prostate Symptom Score (IPSS) and Incontinence Quality of Life Questionnaire (I-QoL) were recorded and compared between the two groups before and after treatment. The adverse reactions were observed. 【Results】 The scores of ICIQ-SF, IPSS and I-QoL and 1 h pad test significantly decreased in both groups after treatment (P0.05), but after treatment, the scores of ICIQ-SF,IPSS,I-QoL and 1 h pad test were significantly lower in the test group than in the control group (P<0.05). No severe adverse reactions were observed. 【Conclusion】 Pelvic floor magnetic stimulation combined with Kegel exercise training is safe and effective for SUI after minimally invasive surgery for BPH.

The Construction of Human Health Community from the Perspective of Marx’s Space Theory: Challenges, Connotations, and Approaches / 中国医学伦理学

Capital’s penetration and mastery of global space shape a human health space that coexists with homogeneity and fragmentation, compressibility and expansion, digestion and remodeling. Capital exacerbates the deprivation of health resources in the global space through means such as controlling the power field, expanding the scope of flow, and monopolizing resource allocation, seriously constraining the overall improvement of human health. The human health community focuses on the healthy development of health in the global space, showing strong human sentiments and profound spatial implications. It aims to break the dominance of capital forces on human health in space, scientifically respond to the space crises caused by major public health events, and build a global space for the balanced and sustainable development of human health. It is Chinese concept, Chinese plan, and Chinese wisdom for reshaping the global justice space and safeguarding human health. To realize the value of health in the global space, it is necessary to take Marx’s space theory as the guide, continuously promote the construction of human health community from the three-dimensional space of individual micro, regional meso, and global macro, and create a space for health justice.

Associations of genetic variants in M3 receptor with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

Associations of genetic polymorphisms in Corin with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

Association between residual cholesterol and the risk of subclinical renal damage / 西安交通大学学报(医学版)

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

Exploring the Principles， Limitations， and Error-Correction Methods of Traditional Chinese Medicine's Empirical Thinking / 中医杂志

From the perspective of cybernetics， this study investigated the fundamental principles of empirical thinking in traditional Chinese medicine， encompassing six stages： experience input and storage， experience extraction and activation， experience combination and reconstruction， judgment and decision-making based on experience， and experience evaluation and feedback. The potential limitations of empirical thinking in clinical applications were analyzed， mainly manifested as “individuality”， “superficiality”， “conservatism”， “prioritizing commonality over individuality”， and “cognitive inertia”. To overcome these limitations， this paper also explored strategies and methods for clinical error-correction from four points： the integration of rational and empirical thinking， the reinforcement of feedback mechanisms and transcendent correction， the integration of individualization and quantity-quality balance， and the management and transference of tacit knowledge under empirical thinking.

Combining neutrophil-lymphocyte ratio and platelet-lymphocyte ratio predicted the prognosis of hepatocellular carcinoma patients after liver transplantation / 中华器官移植杂志

Objective:To explore the prognostic values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio(PLR)and NLR-PLR score for carcinoma(HCC)patients undergoing liver transplantation(LT).Methods:From July 2015 to October 2021, clinical data are retrospectively reviewed for 110 HCC patients undergoing orthotopic LT at Third Hospital of Hebei Medical University.The values of NLR and PLR were calculated.And the cut-off values of NLR and PLR were obtained by receiver operating characteristic (ROC) curve and then grouped according to the cut-off values.Survival time is analyzed by Kaplan-Meier method and Log-rank test performed for inter-group comparison.Univariate and multivariate analyses are performed based on Cox proportional risk regression model.NLR <3.37 and PLR <105.96 are denoted as 0 point while NLR ≥3.37 and PLR ≥105.96 as 1 point.Two points are added up as NLR-PLR score.According to NLR-PLR score, they are divided into 3 groups of 0, 1 and 2.Results:Median overall survival(OS)is 27 months in patients with NLR-PLR score 0, 26.5 months in patients with NLR-PLR score 1 and 6 months in patients with NLR-PLR score 2.Median OS in patients with NLR-PLR score 2 is significantly shorter than that in those with NLR-PLR score 0/1.And the difference is statistically significant( P<0.001).Median disease-free survival(DFS)is 24.5 months in NLR-PLR 0 group, 24 months in NLR-PLR 1 group and 6 months in NLR-PLR 2 group.The difference is statistically significant( P=0.002).Univariate analysis show that Child-Pugh grade, MELD score, NLR/PLR level, NLR-PLR score, complying with University of California San Francisco Criteria(UCSF)criteria and absence/presence of microvascular invasion(MVI)have an impact on patient survival.Further multivariate analysis show that NLR-PLR score, complying with UCSF criteria and MELD score are independent risk factors affecting patients' prognosis and survival. Conclusions:NLR, PLR and NLR-PLR score may predict long-term survival of patients.And NLR-PLR score is an independent risk factor for patient survival.It has more predictive value than NLR/PLR.

Strategy of long-term anti-HBV treatment after liver transplantation for patients with HBV related liver disease / 中华普通外科杂志

Objective:To evaluate the risk of HBV recurrence after liver transplantation in patients with end-stage hepatitis B related liver disease, and to explore the indications for antiviral therapy withdrawal.Methods:The data of HBV DNA, cccDNA in liver puncture tissues and peripheral blood in 31 patients after liver transplantation was retrospectively analyzed.Results:Among the 31 patients, 15 (48%) had detectable and quantified HBV DNA in liver biopsy tissue, while their HBV related serological indicators were negative, suggesting an occult HBV infection in some patients. The study found 15 out of 19 cases who were taking Entecavir were cccDNA negative (78.9%), compared to 5 out of 12 cases (41.6%) in Lamivudine regiment ( P=0.03). Conclusions:Hidden HBV infection can be detected by amplifying cccDNA and HBV DNA in liver puncture tissue by using ddPCR. Entecavir is superior to lamivudine in the clearance of cccDNA.