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:This study investigates the effect of signal-to-noise ratio (SNR), frequency, and bandwidth on horizontal sound localization accuracy in normal-hearing young adults.Methods:From August 2022 to December 2022, a total of 20 normal-hearing young adults, including 7 males and 13 females, with an age range of 20 to 35 years and a mean age of 25.4 years, were selected to participate in horizontal azimuth recognition tests under both quiet and noisy conditions. Six narrowband filtered noise stimuli were used with central frequencies (CF) of 250, 2 000, and 4 000 Hz and bandwidths of 1/6 and 1 octave. Continuous broadband white noise was used as the background masker, and the signal-to-noise ratio (SNR) was 0, -3, and -12 dB. The root-mean-square error (RMS error) was used to measure sound localization accuracy, with smaller values indicating higher accuracy. Friedman test was used to compare the effects of SNR and CF on sound localization accuracy, and Wilcoxon signed-rank test was used to compare the impact of the two bandwidths on sound localization accuracy in noise.Results:In a quiet environment, the RMS error in horizontal azimuth in normal-hearing young adults ranged from 4.3 to 8.1 degrees. Sound localization accuracy decreased with decreasing SNR: at 0 dB SNR (range: 5.3-12.9 degrees), the difference from the quiet condition was not significant ( P>0.05); however, at -3 dB (range: 7.3-16.8 degrees) and -12 dB SNR (range: 9.4-41.2 degrees), sound localization accuracy significantly decreased compared to the quiet condition (all P<0.01). Under noisy conditions, there were differences in sound localization accuracy among stimuli with different frequencies and bandwidths, with higher frequencies performing the worst, followed by middle frequencies, and lower frequencies performing the best, with significant differences (all P<0.01). Sound localization accuracy for 1/6 octave stimuli was more susceptible to noise interference than 1 octave stimuli (all P<0.01). Conclusions:The ability of normal-hearing young adults to localize sound in the horizontal plane in the presence of noise is influenced by SNR, CF, and bandwidth. Noise with SNRs of ≥-3 dB can lead to decreased accuracy in narrowband sound localization. Higher CF signals and narrower bandwidths are more susceptible to noise interference.

Objective:To evaluate auditory spatial discrimination capabilities in patients with mild to moderately severe symmetrical sensorineural hearing loss (SNHL) and to compare the impact of different psychophysical testing methods on Minimum Audible Angle (MAA) and test duration.Methods:A total of 105 symmetrical SNHL patients aged from 18 to 60 years old were enrolled from April to July 2023, including 56 males and 49 females. They were divided into three groups based on PTA: mild, moderate, and moderately severe hearing loss, with 35 individuals in each group. Additionally, a control group of 35 individuals with normal hearing was tested, including 18 males and 17 females. Participants underwent four distinct psychophysical discrimination tests: the block up-down, 1-up/1-down, 1-up/2-down, and 1-up/3-down procedures. We recorded the MAA and test duration for each. We employed repeated measures of ANOVA to compare the MAA and test duration across different methods and groups, and Pearson′s correlation to assess the relationship between MAA and degree of hearing loss.Results:MAA of sound localization in patients with symmetrical SNHL was significantly positively correlated with the degree of hearing loss ( r=0.59, P<0.01). Significant deterioration in MAA was observed as hearing loss progressed to the moderate level (PTA≥35 dBHL, P<0.01). The testing methods significantly influenced MAA and testing duration ( F=24.02, P<0.01; F=75.56, P<0.01) and the 1-up/1-down method was the quickest, averaging only (0.69±0.32) mins. Conclusions:The horizontal plane auditory spatial discrimination abilities in patients with symmetrical SNHL is impaired progressively with increasing hearing loss, notably beyond moderate hearing loss levels. Different psychophysical methods influence both MAA and test duration, the quicker 1-up/1-down method is recommended for assessing MAA in symmetrical SNHL patients.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis(UC).Methods UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract,and their targets were screened using public databases for construction of the core protein-protein interaction(PPI)network and GO and KEGG enrichment analyses.Forty male C57 mice were randomized into normal control group,model group,mesalazine group and Cynanchum wilfordii group(n=10),and in the latter 3 groups,mouse UC models were established by treatment with 2.5%DSS and the latter 2 groups drug interventions by gavage.The therapeutic effect was evaluated by recording body weight changes and DAI score.Pathological changes of the colon tissue were observed with HE and AB-PAS staining,and JAK2 and STAT3 protein expressions were detected with Western blotting.The metabolites and metabolic pathways were identified by metabonomics analysis.Results We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts,including 19 steroids.A total of 177 Cynanchum wilfordii targets,5406 UC genes,and 117 intersection genes were obtained.JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways.Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice(P<0.05),alleviated intestinal pathologies,and decreased JAK2 and STAT3 protein expressions in the colon tissues.Most of the 83 intersecting differential metabolites between the control,model and Cynanchum wilfordii groups were identified as glycerophospholipids,arachidonic acid,and amino acids involving glycerophospholipid metabolism and other pathways.Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites.Conclusion Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.

Objective To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis(UC).Methods UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract,and their targets were screened using public databases for construction of the core protein-protein interaction(PPI)network and GO and KEGG enrichment analyses.Forty male C57 mice were randomized into normal control group,model group,mesalazine group and Cynanchum wilfordii group(n=10),and in the latter 3 groups,mouse UC models were established by treatment with 2.5%DSS and the latter 2 groups drug interventions by gavage.The therapeutic effect was evaluated by recording body weight changes and DAI score.Pathological changes of the colon tissue were observed with HE and AB-PAS staining,and JAK2 and STAT3 protein expressions were detected with Western blotting.The metabolites and metabolic pathways were identified by metabonomics analysis.Results We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts,including 19 steroids.A total of 177 Cynanchum wilfordii targets,5406 UC genes,and 117 intersection genes were obtained.JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways.Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice(P<0.05),alleviated intestinal pathologies,and decreased JAK2 and STAT3 protein expressions in the colon tissues.Most of the 83 intersecting differential metabolites between the control,model and Cynanchum wilfordii groups were identified as glycerophospholipids,arachidonic acid,and amino acids involving glycerophospholipid metabolism and other pathways.Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites.Conclusion Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.