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.

Ginsenoside Rg_2(GRg2) is a triterpenoid compound found in Panax notoginseng. This study explored its effects and mechanisms on diabetic retinopathy and angiogenesis. The study employed endothelial cell models induced by glucose or vascular endothelial growth factor(VEGF), the chorioallantoic membrane(CAM) model, the oxygen-induced retinopathy(OIR) mouse model, and the db/db mouse model to evaluate the therapeutic effects of GRg2 on diabetic retinopathy and angiogenesis. Transwell assays and endothelial tube formation experiments were conducted to assess cell migration and tube formation, while vascular area measurements were applied to detect angiogenesis. The impact of GRg2 on the retinal structure and function of db/db mice was evaluated through retinal thickness and electroretinogram(ERG) analyses. The study investigated the mechanisms of GRg2 by analyzing the activation of Yes-associated protein(YAP) and Toll-like receptors(TLRs) pathways. The results indicated that GRg2 significantly reduced cell migration numbers and tube formation lengths in vitro. In the CAM model, GRg2 exhibited a dose-dependent decrease in the vascular area ratio. In the OIR model, GRg2 notably decreased the avascular and neovascular areas, ameliorating retinal structural disarray. In the db/db mouse model, GRg2 increased the total retinal thickness and enhanced the amplitudes of the a-wave, b-wave, and oscillatory potentials(OPs) in the ERG, improving retinal structural disarray. Transcriptomic analysis revealed that the TLR signaling pathway was significantly down-regulated following YAP knockdown, with PCR results consistent with the transcriptome sequencing findings. Concurrently, GRg2 downregulated the expression of Toll-like receptor 4(TLR4), TNF receptor-associated factor 6(TRAF6), and nuclear factor-kappaB(NF-κB) proteins in high-glucose-induced endothelial cells. Collectively, GRg2 inhibits cell migration and tube formation and significantly reduces angiogenesis in CAM and OIR models, improving retinal structure and function in db/db mice, with its pharmacological mechanism likely involving the down-regulation of YAP expression.
Animals ; Ginsenosides/pharmacology* ; Diabetic Retinopathy/physiopathology* ; Mice ; YAP-Signaling Proteins ; Humans ; Male ; Signal Transduction/drug effects* ; Cell Movement/drug effects* ; Adaptor Proteins, Signal Transducing/genetics* ; Mice, Inbred C57BL ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Panax notoginseng/chemistry* ; Endothelial Cells/metabolism* ; Transcription Factors/genetics* ; Angiogenesis

OBJECTIVE: To explore the improvement effect of rehabilitation nursing based on information-knowledge-belief-behavior (IKAP) theory on urinary incontinence patients after radical prostatectomy. METHODS Sixty-six patients with urinary incontinence who received robot-assisted laparoscopic radical prostatectomy in General Hospital of Eastern Theater Command from January 2021 to January 2023 were selected and divided into control group (n=33) and observation group (n=33) according to random number table method. The patients in the control group were treated with rehabilitation nursing. The patients in the observation group were treated with rehabilitation nursing guided by IKAP theory. The recovery of urinary incontinence, duration of urinary incontinence, subjective well-being, quality of life, psychological and emotional indexes of patients in the two groups were compared. Results： The total effective rate of urinary incontinence recovery in the observation group was significantly higher than that in the control group (90.91% vs 60.61%，P<0.05). The duration of urinary incontinence in the observation group was significantly shorter than that in the control group (［3.36±1.54］d vs ［4.15±1.36］d，P<0.05). And the subjective well-being score in observation group was significantly higher than that in the control group (［19.36±2.69］points vs ［11.65±2.65］points， P<0.05). There was no significant difference in preoperative physical function, social function，and mental health scores between the two groups (P>0.05). And all scores in the observation group were significantly higher than those in the control group after surgery (P<0.05). There was no significant difference in the preoperative SAS and SDS scores between the two groups of patients (P>0.05). And the scores of SAS and SDS in observation group were lower than those of the control group after the operation (P<0.05). Conclusion： Rehabilitation nursing based on IKAP theory can significantly improve urinary incontinence in patients with prostate cancer after surgery, which promotes the recovery of urinary incontinence, shortens the time of urinary incontinence, and improves the subjective well-being and quality of life, as well as reduces the negative impact of negative emotions. Therefore, it can be widely promoted and implemented in clinical practice.
Humans ; Prostatectomy/adverse effects* ; Urinary Incontinence/etiology* ; Male ; Quality of Life ; Rehabilitation Nursing ; Middle Aged ; Aged

BACKGROUND: Hyperthermia (HT), while a cancer treatment approach, isn't always effective alone. Therefore, identifying hyperthermia enhancers is crucial. We demonstrated that Mito-TEMPO ([2-[(1-Hydroxy-2,2,6,6-tetramethylpiperidin-4-yl) amino]-2-oxoethyl]-triphenylphosphanium, MT) acts as a potent thermosensitizer, promoting cell death in human cervical cancer (HeLa) cells. METHODS: Cells were pretreated with 0.4 mM MT for 5 minutes, followed by exposure to hyperthermia (42 °C for 60 minutes). The impacts of MT/HT on cell viability, proliferation, apoptosis, endoplasmic reticulum (ER) stress, apoptosis-related proteins and autophagy, autophagy-related proteins expression were measured. The relationships between autophagy and apoptosis were further investigated using the specific autophagy inhibitor chloroquine (CQ) and the autophagy inducer rapamycin (Rapa). RESULTS: The combined treatment reduced the mitochondrial membrane potential (MMP) and increased ROS production. It also upregulated the pro-apoptotic protein Bax and downregulated anti-apoptotic proteins such as Bcl-2 and MCL-1. As a result, Caspase-3 was activated. Additionally, the combined treatment upregulated the expression of p-PERK/PERK, ATF-4, CHOP proteins. Moreover, the combined treatment also increased the expression of LC3 II and p62, decreased expression of LAMP 1 and Cathepsin D and increased lysosomal pH, indicating coordinated changes in autophagy regulation. Notably, intensification of apoptosis induced by the combined treatment was observed with CQ, whereas attenuation was seen with Rapa. CONCLUSIONS MT effectively enhanced HT-induced apoptosis in HeLa cells. Elevated ER stress and interruption of autophagy flux are the possible underlying molecular mechanisms for this phenomenon. These findings suggested MT can act as a potential thermosensitizer, highlighting its versatility in cancer treatment strategies.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; HeLa Cells ; Uterine Cervical Neoplasms/therapy* ; Female ; Hyperthermia, Induced ; Spin Labels ; Endoplasmic Reticulum Stress/drug effects* ; Cyclic N-Oxides/pharmacology* ; Cell Survival/drug effects*

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objective To investigate the correlation between the attenuation of periappendiceal fat density and its relative CT value(rCT)with the severity of appendicitis,and whether rCT can evaluate the severity of acute appendicitis(AA).Methods A retro-spective selection was made of 79 patients who underwent whole-abdominal CT scans and were pathologically diagnosed with A A(45 with noncomplex A A,34 with complex AA)and 30 normal control group(NCG).Appendicitis-associated signs were recorded and the CT number of periappendiceal fat(CTa),CT number of mesenteric fat gap(CTm),CT number of abdominal anterior wall subcutaneous fat(CTaw),CT number of abdominal posterior wall subcutaneous fat(CTpw),CT number of retroperitoneal fat(CTrp),CT number of gluteal subcutaneous fat(CTgl),and CT number of psoasmajor muscle(CTps)were measured.The ratio of CTa to the CT values of the other 6 parts were calculated,defined as the rCT.Statistical analysis was performed using SPSS 20.0 soft-ware,and the differences were considered statistically significant at P＜0.05.Results Compared among the three groups,statistical differences were found between every two groups in CTa,rCTm,rCTaw,rCTpw,rCTrp,rCTgl,and rCTps(P＜0.05),and the rCT was the lowest in complex AA,followed by noncomplex A A.Receiver operating characteristic(ROC)curve analysis showed that rCTm,rCTaw,rCTpw,rCTrp,rCTgl,rCTps had diagnostic predictive value for both noncomplex AA and complex AA(P＜0.05).Conclusion The attenuation of periappendiceal fat density is associated with the severity of appendicitis,and rCT has certain diagnos-tic predictive value for assessing the severity of appendicitis.The diagnosis of noncomplex AA and complex AA is based on the 95％ confidence interval of rCT.

AIM To investigate the effects of Yunpi Tongchang Formula on intestinal mucosal barrier damage in rats with opioid-induced constipation(OIC)of Spleen-Kidney Yang Deficiency Syndrome.METHODS In contrast to the 10 rats of the blank group,the 50 rats of the modeling group were induced into models of OIC of Spleen-Kidney Yang Deficiency Pattern by 7 days consecutive administration of both subcutaneous loperamide injection and alternating gavage of activated carbon ice water and vinegar.Following successful modeling,rats were randomly allocated into the model group,the mosapride citrate tablet group(1.35 mg/kg),and the high-dose,medium-dose,and low-dose Yunpi Tongchang Formula groups(15.12,7.56,3.78 g/kg),with 8 mice in each group.Upon the completion of the 14 days treatment,the rats had their TCM Syndrome scores assessed;their fecal water content,initial black stool excretion time,and small intestine propulsion rate measured;their colon tissue morphology observed by HE staining;their serum levels of IL-6,TNF-α,and IL-1β detected by ELISA;their expressions of occludin and zonula occludens-1(ZO-1)in colon tissues detected by immunohistochemistry;their mRNA expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by RT-qPCR;and their protein expressions of MyD88,TLR4 and NF-κB p65 in the colon tissues detected by Western blot.RESULTS Compared to the blank group,the model group had higher TCM Syndrome scores(P＜0.01);lower fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);longer initial black stool excretion time(P＜0.01);more mucosal edema in colon tissue,obvious inflammatory infiltration,and glandular disorder;increased serum levels of IL-6,TNF-α and IL-1 β(P＜0.05);decreased colon expressions of ZO-1 and occludin(P＜0.01);and increased mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.01).Compared to the model group,both the medium-dose Yunpi Tongchang Formula group and the mosapride citrate tablet group demonstrated effectively reduced TCM syndrome scores(P＜0.01);increased fecal water content and small intestine propulsion rate(P＜0.05,P＜0.01);and shorter initial black stool excretion time(P＜0.01);improved colon mucosal edema and inflammatory infiltration;decreased serum levels of IL-6,TNF-α and IL-1β(P＜0.01);upregulated protein expressions of ZO-1 and occludin(P＜0.01);and downregulated mRNA and protein expressions of TLR4,MyD88 and NF-κB p65(P＜0.05,P＜0.01).CONCLUSION Yunpi Tongchang Formula significantly ameliorates constipation symptoms in OIC rat models of Spleen-Kidney Yang Deficiency Syndrome because of its efficacy in attenuating intestinal inflammation and preserving the integrity of intestinal epithelial barrier structure,with its mechanistic action in downregulating TLR4/MyD88/NF-κB signaling pathway activation.

Objective To investigate predictive factors of malignant risk for follicular thyroid neoplasms(FTN)with a maximum diameter≤4 cm,providing evidence for preoperative diagnosis and individualized treatment for FTN patients.Methods We retrospectively analyzed clinical data of FTN patients with a maximum tumor diameter≤4 cm treated at our hospital between January 2018 and December 2023.Based on postoperative pathological diagnosis,the patients were divided into follicular thyroid carcinoma(FTC)group and follicular thyroid adenoma(FTA)group.Univariate and multivariate logistic regression analyses were performed to explore predictive factors of malignant risk of FTN.Results A total of 870 patients were included,comprising of 745 patients(85.6%)in the FTA group and125 patients(14.4%)in the FTC group.The univariate analysis showed thatage,gender,BMI,comorbidity of Hashimoto's thyroiditis,number and location of nodules,the maximum diameter of nodules,internal structure of nodules,and internal blood flow signals had no significant differences(P>0.05),while nodule echogenicity,margins,halo,taller-than-wide shape,and calcification had significant differences(P<0.05).Multivariate logistic regression analysis revealed that irregular margins(OR=3.061,95%CI:1.653-5.667,P=0.000),uneven thickness of the halo(OR=5.868,95%CI:1.258-27.377,P=0.024),and peripheral rim calcification(OR=4.364,95%CI:1.329-14.333,P=0.015)were predictive factors of malignant risk for FTC.Conclusions Ultrasound features have certain value for evaluating benign or malignant nature of FTN.Careful assessment of nodule margins,halo,and calcification can facilitate early diagnosis and treatment of small FTN.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.