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.

We reported a 32 years female patient in whom lung metastasis from breast cancer was presented as solitary pulmonary pure ground-glass opacity (GGO) lesion. The patient received rational preoperative examinations and surgery though the preoperative diagnosis was not accurate. Because of different therapy strategies and purposes, it is crucial to make distinction of atypical metastases from primary cancers. Thus, for patients with a history of malignancy, possible metastasis should be taken into consideration if new GGO was found on the CT. Besides this, the follow-up interval of CT should be shortened appropriately, preoperative examinations and surgical procedures should be made according to the suggestions of multidisciplinary team.

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Background and purpose:Human epidermal growth factor receptor 2(HER2)is closely associated with drug efficacy and prognosis in urothelial carcinoma(UC).HER2 is a significant biomarker and therapeutic target in various tumors.In recent years,anti-HER2 antibody-drug conjugates have shown significant clinical efficacy in UC patients with HER2 overexpression.Therefore,an in-depth understanding of HER2 expression and its characteristics in Chinese UC patients is crucial to guide treatment decision-making,optimize treatment strategies and achieve personalized therapy.This study aimed to thoroughly investigate correlation of HER2 expression and clinicopathological characteristics in Chinese patients with UC.Methods:This study was a multicenter study that retrospectively included UC patients from urology departments of 8 tertiary hospitals in 5 geographical regions of China(North China,East China,South China,Central China and Northwest)whose tissue samples were collected from January 2023 to March 2024.Inclusion criteria:① age above 18 years;② UC diagnosed by histopathological or cytological examination;③ complete results of HER2 expression detection using immunohistochemistry(IHC)in the primary tumor site were required.Exclusion criteria:① diagnosed patients with tumors in other parts of the body;② physicians evaluated other situations that were not suitable for inclusion in this study.IHC results for HER2 expression and clinicopathological data were collected.HER2 expression was determined according to the criteria outlined in"Clinical pathological expert consensus on HER2 testing in urothelial carcinoma in China",with HER2 2+and 3+defined as HER2 overexpression.The HER2 expression and clinicopathological features were analyzed.This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(ethical number:2301268-12)and was registered at China Clinical Trial Registry(registration number:ChiCTR2300069746).Results:A total of 1054 patients with UC were included.Most of the tumors were bladder UC(n=807,76.6%).The mean age of patients was(66.8±10.5)years,and the majority were male(78.5%).The HER2 overexpression rate was 58.4%(n=616),with an additional 23%of patients having HER2 1+expression(n=242),and a small proportion exhibiting negative HER2 expression(n=196,18.6%).HER2 expression was significantly associated with various clinical and pathological characteristics such as Eastern Cooperative Oncology Group(ECOG)performance status,history of cardiovascular disease,history of metabolic disorders,smoking,UC disease location,differentiation grade,pathological type,and tumor stage.Conclusion:Retrospective analysis of multi-center data shows that HER2 expression is frequently observed in Chinese UC patients,with an overexpression rate of up to 58.4%.Furthermore,HER2 expression is closely associated with various clinical and pathological features of UC patients.This study underscores the critical importance of accurately assessing HER2 expression in UC patient to guide personalized therapies.

ObjectiveTo explore effect of modified Wuhutang on airway inflammation and expression of mucin （Muc） 5AC， signal transducer and activator of transcription 3 （STAT3）， nuclear factor kappa B （NF-κB）， and NOD-like receptor thermal protein domain associated protein 3 （NLRP3） in respiratory syncytial virus （RSV）-infected asthmatic mice. MethodSeventy male BALB/c mice of 6-8 weeks old were randomized into normal control （CON）， asthma （ovalbumin， OVA）， RSV infection-induced asthma （OVA+RSV）， high-， medium-， and low-dose （4.08， 2.04， 1.02 g·kg^-1·d^-1， respectively） modified Wuhutang， and dexamethasone （Dxms， 0.1 g·kg^-1d^-1） groups （n=10）. The model of asthma was established by sensitization and atomization inhalation with OVA. The RSV infection-induced asthma model was established by three consecutive RSV nasal infusions （1.0 × 10⁶ PFU·mL^-1， 50 μL）. Wuhutang was administrated by gavage， and Dxms by intraperitoneal injection. The CON group was given the same amount of normal saline by gavage. The mice were anesthetized with 2.5% pentobarbital sodium 24 h after the last administration， and then the lung tissue was stained by hematoxylin-eosin （HE） and Van Gieson （VG） for observation of airway inflammation. The immunohistochemical assay was employed to detect the expression of Muc5AC. Western blot was employed to determine the protein levels of phosphorylated （p）-STAT3， STAT3， p-NF-κB， NF-κB， and NLRP3. ResultCompared with the CON group， the OVA group presented airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition. The OVA+RSV group showed severer airway inflammatory cell infiltration and tissue hyperemia and edema than the OVA group. Compared with the OVA+RSV group， modified Wuhutang alleviated the airway inflammatory cell infiltration， tissue hyperemia and edema， and collagen fiber deposition， and the high-dose group had the best performance. Compared with the CON group， the OVA group and the OVA+RSV group showed increased expression level of Muc5AC （P<0.01）. Compared with the OVA+RSV group， modified Wuhutang reduced the expression level of Muc5AC， and the reduction was significant in the high-dose group （P<0.05）. Compared with the high-dose modified Wuhutang group， Dxms lowered the expression level of Muc5AC （P<0.05）. Compared with the CON group， the OVA and OVA+RSV groups showed up-regulated protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.05， P<0.01）. Compared with the OVA+RSV group， modified Wuhutang down-regulated the protein levels of p-STAT3， p-NF-κB， and NLRP3 （P<0.01）. Compared with the high-dose modified Wuhutang group， the Dxms group showed up-regulated levels of p-STAT3， p-NF-κB proteins （P<0.01）. ConclusionModified Wuhutang can reduce airway inflammation and down-regulate the expression of Muc5AC， p-STAT3， p-NF-κB， and NLRP3 in RSV-infected asthmatic mice， which suggests that Wuhutang reduces airway inflammation in RSV-infected asthma by regulating the STAT3/NF-κB signaling pathway.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.
Humans ; COVID-19 ; Sleep Initiation and Maintenance Disorders ; Crisis Intervention ; Psychosocial Intervention ; SARS-CoV-2 ; Mental Health ; Depression/epidemiology* ; Health Personnel/psychology* ; Anxiety/etiology*