Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objective:To explore the early coagulation function changes of penetrating intestinal firearm injury of pig in high-altitude environments.Methods:Twenty healthy long white piglets were selected and divided into the plain group and the high-altitude group using the random number table method, with 10 pigs in each group. Pigs in the plain group were placed in a plain environment at an altitude of 800 meters, while pigs in the high-altitude group were placed in an experimental chamber simulating an altitude of 6 000 meters for 48 hours. Both groups received pistol gunshot to have firearm penetrating wounds to the abdominal intestinal tract and then returned to the plain observation room. At 0, 2, 4, 8, 12 and 24 hours after injury, coagulation in the peripheral blood and fibrinolytic indexes [prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg), D-dimer (D-D), and fibrinogen degradation product (FDP)], thromboelastogram (TEG) [reaction time (R), clotting time (K), clot formation rate (α), maximum amplitude (MA) and coagulation composite index (CI) ], platelet parameters [platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR)] in the two groups were detected separately.Results:The PT values at 0 and 2 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours than those in the plain group ( P<0.01); there was no significant difference at 4 hours between the two groups ( P>0.05). The APTT values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The TT values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.01); there was no significant difference at 8 hours after injury between the two groups ( P>0.05). The Fbg, D-D and FDP values at 0, 2, 4, 8, 12 and 24 hours after injury were higher in the high-altitude group than those in the plain group ( P<0.01). The R values at 0, 2 and 4 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The K values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly lower than those in the plain group, while they were significantly higher at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The α angles at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The MA values at 0, 2 and 4 hours after the injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The CI values at 0, 2 and 4 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 8, 12 and 24 hours after injury than those in the plain group ( P<0.01). The PLT values at 0, 2, 4 and 8 hours after injury in the high-altitude group were significantly higher than those in the plain group, while they were significantly lower at 12 and 24 hours after injury than those in the plain group ( P<0.05 or 0.01). The MPV values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.01). The PDW values at 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were significantly higher than those in the plain group ( P<0.05 or 0.01), while there was no significant difference in PDW at 0 hour after injury between the two groups ( P>0.05). The P-LCR values at 0, 2, 4, 8, 12 and 24 hours after injury in the high-altitude group were all significantly higher than those in the plain group ( P<0.01). Conclusion:Compared with the plain environments, pig intestinal firearm penetrating injury in the high-altitude environments is more prone to early hypercoagulable state accompanied by mild hyperfibrinolysis, and faster to reach a hypocoagulable state accompanied by obvious hyperfibrinolysis.

We report a case of a young female patient with fatigue, hypokalemia, and hyperglycemia. She had past-history of diabetes mellitus, and was admitted to hospital with a history of fatigue and hypokalemia for 5 years. The patient's examination indicated hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and SLC12A3 gene pathogenic mutation. The diagnosis was Gitelman syndrome. Potassium and magnesium supplements were given to improve the patient's fatigue. Serum potassium and magnesium were normal. The blood glucose reached standard after treatment with oral hypoglycemic drugs. This article incorporates literature review to sort out the diagnosis and treatment of Gitelman syndrome, in order to provide feasible reference for clinicians.

Objective To investigate the status quo and its influencing factors of nurses'organizational silence in 3 Grade A general hospitals.Methods Convenient sampling method was used to investigate clinical nurses in 3 Grade A general hospitals in Xi'an from April to August 2023 by general data questionnaire,nurses'organizational silence questionnaire and hospital magnetic factor scale.Multiple linear regression was used to analyze the influencing factors of organizational silence.Results A total of 855 nurses completed the study.The total silence score of nurses was(56.33±8.55);The total score of hospital magnetic level was(107.63±12.85).There was a negative correlation between nurse tissue silence and hospital magnetic level(r=-0.318,P<0.01).Hospital magnetic level,age,job title and working time were the influential factors of nurses'organizational silence(all P<0.001),which together explained 62.60%of the variation.Conclusions The silence of nurses'tissue and the level of hospital magnetism are in the low-medium level.Nurses are younger in age,lower in professional title,shorter in nursing age and lower in hospital magnetism level,the higher the tissue age level is,the nursing managers can reduce the tissue silence of nurses by improving the hospital magnetism level.

Objective:To investigate vitamin D levels and the effect of exogenous vitamin D supplementation in the first trimester among pregnant women in our center.Methods:This was a prospective cohort study. A total of 98 women in the first trimester who were followed-up regularly in Peking Union Medical College Hospital from December 1 st 2020 to December 1 st 2021 were enrolled. Subjects who had medical conditions that affect vitamin D absorption or metabolism were excluded. Questionnaires were administered, and 25-hydroxyvitamin D [25(OH)D] levels were detected using liquid chromatography tandem mass spectrometry (LC/MS/MS) method. According to the basic 25(OH)D level, different dosages of exogenous vitamin D were supplemented. After 4 weeks, 25(OH)D levels were detected again to evaluate the effect of supplementation. T test, analysis of variance, χ2 test, and multiple linear regression analysis were used for analysis. Results:The mean age of enrolled subjects was (33.5±4.0) years. The baseline 25(OH)D level was (41.2±20.0) nmol/L. Briefly, 70.4% (69/98) subjects were deficient in vitamin D, and 42.9% (42/98) patients were using vitamin D supplementation at the time of 25(OH)D testing. Single-factor analysis showed that vitamin D supplementation ( t=-4.21, P<0.001), season ( t=2.59, P=0.011), and nut-eating frequency ( t=2.67, P=0.009) were related to 25(OH)D levels. Multiple linear regression analysis showed that only vitamin D supplementation had a relationship with 25(OH)D level ( B=13.84, P=0.006). According to the baseline 25(OH)D level, 400-5 000 U/d vitamin D3 was supplemented regularly for (4.1±2.5) weeks, and 25(OH)D levels significantly increased after supplementation [(64.1±18.1) vs (37.3±16.6) nmol/L, t=-9.36, P<0.001]. The ascending range was negatively associated with basic 25(OH)D level ( B=-0.66, P<0.001) and positively associated with supplementary dosage ( B=0.51, P<0.001). 25(OH)D levels increased by 0.51 nmol/L on average per 1 μg (40 U) of vitamin D supplementation daily. Conclusions:The proportion of vitamin D deficiency was high in the first trimester among pregnant women in our center. Exogenous vitamin D supplementation could significantly increase 25(OH)D levels, and the effect was negatively associated with basic 25(OH)D level but positively associated with supplementary dosage.

Objective:To explore the molecular mechanism of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair for depression and Alzheimer disease (AD) with the same treatment through network pharmacology. Methods:Effective components of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were retrieved from TCMSP, TCMID and ETCM databases. The disease targets of depression and AD were retrieved from GeneCards, TTD and CTD databases. Targets of action of drugs on active components were predicted through SwissTargetPrediction, and then the intersection targets of medicinal pair and the diseases were taken. Cytoscape 3.6.1 was used to construct the interaction network of Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair on "component-common target-disease". The enrichment analysis of GO function and KEGG pathway was carried out with the help of Metascape platform, and molecular docking verification was carried out. Results:Through searching the databases and literature, 78 compounds in Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair were obtained, corresponding to 41 targets of different diseases with the same treatment. The GO function was mainly concentrated in response to lipopolysaccharide and cellular response to nitrogen compound. The KEGG pathway was mainly concentrated in lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on. The core targets were PTGS2, ESR2, etc. Molecular docking showed that most of the core components could form stable conformation with the core targets. Conclusions:Polygalae Radix - Acori Tatarinowii Rhizoma medicinal pair has the characteristics of multi-component, multi-target and multi-pathway in the same treatment of depression and AD. Through their core components of senegenin, 1-carbobutoxy-β-carboline, 6-hydroxy-1,2,3,7-tetramethoxyxanthone, kaempferol and etc., the pair can act on PTGS2 and other targets, regulate lipid and atherosclerosis, calcium signaling pathway, serotonergic synapse, insulin resistance and so on, and play a therapeutic role in depression and Alzheimer's disease with the same treatment.