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.

Primary hyperparathyroidism(PHPT) is relatively rare in individuals before adulthood. Among juvenile patients, hereditary PHPT accounts for a significant proportion. Specifically, infant and toddler patients often carry gene mutations related to the calcium-sensing receptor signaling pathway, whereas children and adolescent patients predominantly exhibit mutations in genes associated with cell proliferation. Notably, PHPT in infants, children, and adolescents differs significantly from that in adult patients in terms of genetic background, clinical manifestations, treatment strategies, and prognosis. This article aims to systematically summarize the genetic characteristics and clinical features of juvenile-onset PHPT to enhance the physicians' understanding of this disease.

Objective To explore the distribution of circuit-qi indicators at birth in the patients with chronic atrophic gastritis(CAG)based on five-circuit and six-qitheory,and to summarize their congenital circuit-qi endowment features,so as to explore treatment strategies for CAG accordingly.Methods From January 2018 to December 2023,a total of 2 046 cases of patients with CAG admitted to Shenzhen Bao'an Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine(i.e.,Shenzhen Bao'an Traditional Chinese Medicine Hospital)were selected,and the distribution of the five-circuit and six-qiindicators at birth in the patients was analyzed by using the SPSS 24.0 statistical software.The features of the congenital circuit-qi endowment were summarized,and then the corresponding treatment strategies were put forward.Results The CAG patients had the highest proportions of circuit-qiendowment features at birth,showing as the yearly circuit being deficiency fire circuit,the dominant circuit being metal circuit,the dominant qibeing yangmingdryness-gold,the guest qibeing taiyangcold-water,and sitianbeing shaoyangminister fire and zaiquanbeing j ueyinwind-wood,and the differences in the distribution of the dominant circuit,dominant qi,and guest qiwere statistically significant(P<0.05 or P<0.01),but differences in the distribution of the yearly circuit and sitian/zaiquanwere not statistically significant(P>0.05).The analysis of the combined circuit-qifeatures at birth showed that the proportion of patients with CAG born in the year of celestial restriction,mildly-rebellious year and disharmony year was the highest,and the proportion of those born in the convergent year and iso-convergent year was the lowest,with statistically significant differences(P<0.05).Conclusion The congenital circuit-qiendowment of patients with CAG is characterized by liver depression and qistagnation,dryness and coldness.Therefore,the treatment for CAG should be from the perspective of the liver,with the method of soothing liver and harmonizing stomach,supplemented by nourishing yin to moisten dryness,and protecting yang qiof the spleen and stomach.The combined use of acup-moxibustion and Chinese medicines is recommended.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

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 evaluate the prognostic values of parameters from hypothermic machine perfusion (HMP) after static cold storage (SCS) on short-term outcomes of kidney transplantation.Method:From February 2023 to October 2023, the authors retrospectively reviewed the clinical and HMP data of recipients undergoing adult deceased donor kidney transplantation at Xuanwu Hospital, Capital Medical University. HMP resistance and renal arterial anatomical variants were utilized for subgroup analysis. The primary endpoints were delayed graft function (DGF) and whether or not creatine level normalized. The secondary endpoints were the lowest creatine level within 1 month post-kidney transplantation, reduction extent of creatinine level, duration for creatine level to decline to the lowest and duration for creatinine normalization. Single and multiple variable analyses were utilized for examining the correlation between HMP parameters and short-term postoperative outcomes.Result:A total of 157 recipients were included for analysis. Mean serum creatinine level was (870.0±283.9) μmol/L and mean trough creatinine level within 1 month postoperatively (118.5±63.5) μmol/L. Sixteen recipients (10.2%) had delayed graft function (DGF) and creatinine failed to normalize in 10 receipients (6.4%). Average time for creatinine to decline to the lowest level within 1 month was (14.5±7.6) d (3~30 d) and average time for creatinine to normalize (6.4±5.8) d (1~30 d). Multiple variable regression analysis revealed that terminal resistant index was independently correlated with multiple events, including DGF ( P<0.01), whether or not creatinine level normalized within 1 month ( P=0.001), reduction extent of creatinine level ( P<0.01) and duration for creatinine normalization ( P=0.024) . Conclusion:Parameters of HMP after SCS are capable of predicting the short-term outcomes of kidney transplantation. Terminal resistant index is an independent risk factor for several prognostic events.