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.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Objective:Surface electromyography was used to observe the activation and co-contraction strategies of mus-cles surrounding the knee in female patients with knee osteoarthritis(KOA)during sitting,standing and step-ping.Method:Female KOA patients admitted to the Affiliated Hospital of Southwest Medical University from March 2023 to January 2024 were recruited.Surface electromyography was used to collect the integral EMG and root mean square values of the vastus medialis,biceps femoris,lateralis femoris,semitendinosus and rec-tus femoris of the affected side of KOA patients during the process of standing to sitting,sitting to standing,ascending and descending steps.The activation of peri-knee muscles and the change of co-contraction strategy were observed in the control group without KOA.Result:Thirty-five KOA patients and 20 control patients were recruited.From sitting to standing,the root mean square(RMS)and integrated electromyography(iEMG)activation of biceps femoris and semitendinosus in KOA group were significantly lower than those in control group(|Z|>3.097,P<0.005),and the co-contraction of hamstring/quadriceps muscle decreased(|Z|=4.164,P<0.001).From standing to sitting,KOA patients had signifi-cantly higher quadriceps and hamstring muscle activation(|Z|>3.009,P<0.005)and decreased medial/lateral co-contraction(|Z|=2.310,P<0.001).During the stair ascent initiation phase,the iEMG levels of lateral femoris,bi-ceps femoris and semitendinosus in KOA group were higher than those in control group(|Z|>2.899,P<0.005).In the following stage,iEMG levels of lateral femoris muscle and rectus femoris muscle were higher than those of control group(|Z|>2.110,P<0.005).During the stair descent initiation phase,the iEMG levels of later-al femoris,biceps femoris and semitendinosus in KOA group were higher than those in control group(|Z|>2.092,P<0.005).In the following stage,iEMG levels of lateral femoris muscle and rectus femoris muscle were higher than those of control group(|Z|>2.606,P<0.005).During stair ascent and descent activities,there was no significant difference in the co-contraction of hamstring and quadriceps,medial and lateral muscles(P>0.05).Conclusion:Middle-aged and elderly women with KOA showed changes in muscle activation intensity and common contraction strategies during functional activities,which varied according to the type of task(sit-stand,stand-sit,stairs activity).

An implantable cardiac monitor(ICM)is a subcutaneous electronic device for recording and remotely transmitting electrocardiographic events.New-generation ICM,like the Reveal LINQ,have extended arrhythmia monitoring duration and improved diagnostic yield through miniaturization,large storage capacity,and easy implantation.They provide comprehensive monitoring data for cardiovascular disease diagnosis and treatment,optimize individualized treatment plans,and enhance patient prognosis.In recent years,research on ICM in cardiovascular fields has deepened,and their clinical application scope has expanded.They show significant advantages and unique value and are widely used in early cardiovascular disease diagnosis and prognostic management.In the future,ICM are expected to play a bigger role in boosting diagnostic and prognostic capabilities for cardiovascular disease patients,offering stronger support for early disease detection,accurate diagnosis,and effective management.

BACKGROUND:Large deep burn wounds are often accompanied by scar hyperplasia after healing,requiring transplantation of medium-thickness skin for repair,and the medium-thickness skin slices taken generally reach below the papillary layer of the dermis.If not handled correctly,complications such as delayed healing,ulceration,and post-healing pain and itching in the donor area can easily occur.Therefore,the repair of wounds in the donor area should be emphasized.OBJECTIVE:To observe the safety and practicability of autologous scalp repair of skin donor area in patients with deep burns and scarring.METHODS:Sixty patients with deep burn and scar hyperplasia admitted to the Burn Department of Zhengzhou First People's Hospital from January 2021 to September 2023 were selected as the study subjects.They all needed medium-thickness skin transplantation and repair,and were divided into study group(n=30)and control group(n=30)according to random systematic sampling method.The skin was taken from the patient's own medium-thickness skin on the leg or back.In the study group,the skin donor area was repaired with self-blade thick scalp replantation,and in the control group,the skin donor area was repaired with absorbent dressing.The wound healing rate and the time to complete epithelialization of the wound were observed and compared in the two groups 6 days after surgery.The pain of dressing change at 3 and 6 days after surgery and scar hyperplasia in the skin donor area at 6 months after surgery were compared between two groups.RESULTS AND CONCLUSION:Compared with the control group,the time to complete epithelialization of the wound was significantly lower in the study group(P<0.05),and the wound healing rate was significantly higher in the study group(P<0.05),the pain score for dressing change at 3 and 6 days after surgery was significantly lower in the study group(P<0.05),and the scar hyperplasia rate,scar score and itch score were also significantly lower in the study group(P<0.05)at 6 months after surgery.In conclusion,autologous scalp repair of the medium-thickness skin donor area can accelerate wound healing and reduce scar hyperplasia.

Aim To identify the chemical components of Angelica sinensis(AS)and explore the mechanism of AS in activating blood circulation.Methods UP-LC-Q-TOF-MS was used to identify the chemical com-ponents of AS.The changes of syndrome and patholog-ical section of heart in rats were observed.Hemody-namics and proteomics were measured.Results A to-tal of 270 compounds were identified from AS.It showed that rats of Angelica sinensis group were greatly improved such as arched back,shrugged fur,huddled up and less mobile,purplish paws and tails,whitish ear margins and nasolabial lips,reduced drinking and feed-ing,and slow response to external stimuli;mildly disor-dered myocardial fibre arrangement,myofibre arrange-ment was tighter than that of model group,myocardial fibres were narrower and close to normal,and mild oe-dema,exudation,and inflammatory cell infiltration could be seen in the surrounding area;SAP was signif-icantly lower and LVSP was significantly higher in An-gelica sinensis group(P＜0.05).Proteomics showed that 62 differential proteins were screened in Angelica sinensis group compared to model,GO function were concentrated in the extracellular matrix,cytoskeletal proteins binding and protein hydrolysis negatively regu-lated.KEGG pathway were enriched in signalling path-ways such as complement and coagulation cascades,cellular focal adhesion,leukocyte transendothelial mi-gration and chemokine signalling pathways.Conclu-sions AS probably through the expression of proteins,which modulate the signalling pathways of the comple-ment and coagulation cascade reactions and the con-traction of vascular smooth muscle.

Objective:To assess the carrier frequency of spinal muscular atrophy (SMA) in women of childbearing age in Chongqing and to evaluate prenatal diagnostic outcomes in high-risk couples.Methods:A total of 17 926 women of childbearing age attending Chongqing Health Center for Women and Children between May 2021 and November 2023 were enrolled, including 3 398 pre-pregnant women and 14 528 pregnant women, all of whom had no clinical phenotype or family history of SMA or related neuromuscular disorders. Real-time quantitative PCR (RT-qPCR) was used to determine the copy number variations in exons 7 and 8 (E7, E8) of the SMN1 gene. High-risk carriers were identified based on the genetic screening results. Multiplex ligation-dependent probe amplification (MLPA) was employed for prenatal diagnosis of fetuses from high-risk couples. This study was approved by the Medical Ethics Committee of Chongqing Health Center for Women and Children (Ethics No.2021-RGI-02). Results:① Among the 17 926 women of childbearing age, 298 (1.66%) were identified as heterozygous carriers, including 278 (1.55%) with concurrent deletions of E7 and E8, and 20 (0.11%) with isolated deletions of E7. ② Seven high-risk couples were identified, six of whom were prenatal couples. Of the two fetuses from these high-risk pregnancies, both exhibited heterozygous deletions of E7 and E8 in the SMN1 gene, while four fetuses showed no abnormalities. Conclusion:This study provides a comprehensive assessment of the carrier frequency of SMA among women of childbearing age in Chongqing, offering valuable data for the primary and secondary prevention of SMA-related birth defects in the region.

Albendazole-glucan particles(ABZ-GPS)and abendazole(ABZ)were used to treat secondary alveolar echinococ-cosis in mice.The therapeutic effects of ABZ-GPS on alveolar echinococcosis in vivo were evaluated,and the feasibility of using glucan particles as anti-hydatid drug carriers was further verified.Mice with echinococcosis were randomly divided into an ABZ group,glucan nanoparticle(GP)group,ABZ-GPS group,and control group.After four courses of administration with a final concentration of 50 mg/mL,the therapeutic effects of ABZ-GPS were evaluated on the basis of imaging,histopathological changes,ultrastructure,and immunology.After ABZ-GPS and ABZ administration,clear liver lesion tissue necrosis and large numbers of infiltrating lymphocytes were observed.Significant differences in the average cyst wet weight(t=7.83,P＜0.05),were observed between the ABZ-GPS group and ABZ group.Imaging revealed that ABZ-GPs were targeted to liver tissue.Pa-thology and ultrastructure analyses demonstrated that the alveolar hydatid cells in the liver in the control group and GP group grew well,and the vesicles were large,filled with cystic fluid,and translucent or transparent;the cyst wall tension was high;no calcification was observed;the stratum corneum and germinal layer were clear;and more fertile capsules and different num-bers of protocephalospora were present in the liver.In the ABZ group,the capsular cavity collapsed,and showed partial necro-sis and lymphocyte infiltration.In the ABZ-GP group,the corneum and germinal layer of echinococcus vesicles were difficult to identify,and we observed bulbous necrosis,central calcification,fibrous tissue hyperplasia,inflammatory cell infiltration,coarser,shorter or absent microvilli of the germinal layer,nuclear shrinkage,dissolution or disappearance,clear expansion of cytoplasmic microtubules,and myelin-like or vacuole-like changes.Therefore,ABZ-GPs showed good targeting and killing ac-tivity in vivo in mice with secondary alveolar coccosis.

ObjectiveTo explore the potential mechanism of Xixin Decoction （洗心汤， XD） in treating Alzheimer's disease （AD）. MethodsXD-containing serum was prepared， and the BV-2 microglial cell viability was assessed using the CCK8 assay to determine the optimal intervention concentrations of XD-containing serum and amyloid-beta _25-35 （Aβ_25-35） for subsequent experiments. BV-2 cells were divided into four groups， control group， model group （Aβ_25-35）， XD-containing serum group （Aβ_25-35+ XD-containing serum）， and blank serum group （Aβ_25-35 + blank serum）. After 24 hours of culture， the levels of interleukin-1β（IL-1β）， cyclooxygenase-2 （COX-2）， and arginase-2 （Arg-2） in the supernatent were detected by ELISA. Immunofluorescence staining was performed to detect the protein levels of ionized calcium-binding adaptor molecule 1 （IBA1）， CD86， and CD206. RT-PCR was used to analyze the mRNA expression of IL-1β， interleukin-6 （IL-6）， and interleukin-10 （IL-10）. ResultsThe concentrations of 10% XD-containing serum and 40 μmol·L^-¹ Aβ_25-35 were selected for subsequent experiments. Compared to the control group， the model group showed significantly increased levels of IL-1β and COX-2 in the supernatant， as well as elevated protein expression of IBA1 and CD86 and increased mRNA expression of IL-1β and IL-6， while exhibiting significantly reduced levels of Arg-2 in the supernatant， CD206 protein expression， and IL-10 mRNA expression （P＜0.05 or P＜0.01）. Compared to the model group， the XD-containing serum group showed significant improvement in all these indicators （P＜0.01）， whereas no statistically significant differences were observed in the blank serum group （P＞0.05）. ConclusionXD may regulate microglial activation， inhibit pro-inflammatory factors， and enhance anti-inflammatory factor release， thereby improving neuroimmune inflammation and inhibiting the progression of Alzheimer's disease.

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.