ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

OBJECTIVE: To observe the clinical efficacy and safety of automatic pressure-controlled pressure cupping in patients with lumbar disc herniation, and compare it with traditional cupping. METHODS: A total of 100 patients diagnosed with lumbar disc herniation from January 2022 to August 2024 were selected and divided into two groups:the automatic pressure-controlled pressure cupping group (controlled pressure cupping group) and the traditional cupping group (control group), 50 cases in each group. In the controlled pressure cupping group, there were 18 males and 32 females, with an age of (51.98±12.69) years;in the control group, there were 16 males and 34 females, with an age of (51.32±12.05) years. The visual analogue scale(VAS), comfort score, and lumbar range of motion were observed before treatment and after the 1st, 3rd, and 7th treatments to evaluate the efficacy and safety. RESULTS: All patients completed the treatment intervention, with complete follow-up data collected. No adverse reactions or complications occurred during treatment and follow-up. After the 3rd treatment, the VAS score of the controlled pressure cupping group was (2.38±0.49), which was lower than that of the control group (2.94±0.68), with a statistically significant difference (P<0.001). In the controlled pressure cupping group, the VAS scores after the 1st, 3rd, and 7th treatments were significantly better than those before treatment (P=0.026);in the control group, the VAS scores after the 3rd and 7th treatments were better than those before treatment, but the difference was not statistically significant(P=0.182). Repeated-measures analysis of variance (ANOVA) on VAS scores at different time points in both groups showed that there were statistically significant differences in inter-group, time, and interaction effects (P<0.05). After the 1st treatment, in the controlled pressure cupping group, 0 patients felt comfortable, 42 patients (84%) felt mild discomfort, and 8 patients (16%) felt moderate discomfort;in the control group, 0 patients felt comfortable, 28 patients (56%) felt mild discomfort, and 22 patients(44%) felt moderate discomfort;the difference between the two groups was statistically significant(P=0.005). After the 3rd treatment, in the controlled pressure cupping group, 30 patients(60%) felt comfortable, 20 patients (40%) felt mild discomfort, and 0 patients felt moderate discomfort; in the control group, 9 patients (18%) felt comfortable, 41 patients (82%) felt mild discomfort, and 0 patients felt moderate discomfort;the difference between the two groups was statistically significant(P<0.001). There was no statistically significant difference in comfort between the two groups after the 7th treatment(P>0.001). There was no statistically significant difference in lumbar range of motion between the two groups before and after treatment(P>0.05);compared with before treatment, the lumbar range of motion of both groups after treatment was significantly improved, with statistically significant differences (P<0.001). CONCLUSION Automatic pressure-controlled pressure cupping can effectively relieve symptoms in patients with lumbar disc herniation, with excellent safety.
Humans ; Female ; Male ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae/physiopathology* ; Cupping Therapy/methods* ; Pressure ; Aged ; Treatment Outcome

Objective:To summarize the ultrasonographic features and prognosis of fetal persistent vitelline artery.Methods:The prenatal ultrasound features, genetic testing results, and prognosis of a fetus with an isolated persistent vitelline artery that was diagnosed in our hospital in December 2021 were retrospectively analyzed. Relevant articles were retrieved from CNKI, VIP, Wanfang, Yiigle, PubMed, Embase, and UpToDate databases using the terms "persistent vitelline artery", "type Ⅱ single umbilical artery", and "prenatal ultrasound" in both Chinese and English. Prenatal ultrasound features and prognosis of the persistent vitelline artery in fetuses were summarized using descriptive statistical analysis.Results:(1) Case report: In this case, ultrasound at 23 gestational weeks showed that an abnormally large blood vessel deriving from the celiac artery near the superior mesenteric artery entered the placenta through the umbilical opening in parallel with the umbilical vein. Color Doppler showed a blood flow spectrum like that in the umbilical artery. The transverse section image showed that bilateral umbilical arteries were not observed in the bladder and the free segment of the umbilical cord was in the shape of the Chinese character "Lyu". No obvious other structural abnormalities and a negative result of genetic testing were observed in the fetus. Followed up to one year old, the patient showed normal growth and development. (2) Literature review: A total of five articles involving four cases were retrieved (three in English and two in Chinese). Among the five cases, including the present case, one was terminated due to left renal agenesis and abnormal heart arteries ratio revealed by prenatal ultrasound, and the remaining four cases without obvious structural abnormalities in the prenatal ultrasound were born and developed well. Histopathological examination of the umbilical cord was performed in three cases, of which two with persistent vitelline artery had a distinct internal elastic lamina, and one with remained vitelline duct.Conclusions:The prenatal ultrasound of fetal persistent vitelline artery is typically characterized by an abnormal vessel that is derived from the abdominal aorta or superior mesenteric artery and plays the function of the umbilical artery. The prognosis of the isolated persistent vitelline artery is good, but a better understanding of such embryonic abnormalities is needed as there are few relevant reports at home and abroad.

The purpose of this study was to understand the prevalence of Neoehrlichia mikurensis in rodents in Yunnan commensal rodent plague foci.Lianghe Country,Mangshi City,and Mile City in Yunnan Province were chosen as sampling sites,where rodents were captured with dead-traps.The N.mikurensis groEL gene in rodent spleen samples was detected with nested PCR,and the positive products were sequenced with Sanger bidirectional assays.The infection rate of N.mikurensis a-mong plague foci,habitats,species,and sexes was compared with Chi-square tests or Fisher's exact probability method.Of 656 rodent spleen samples,12 N.mikurensis positive samples were detected in R.tanezumi,R.sladeni,N.confucianus,and B.bowersi.The positivity rate was 1.83％.No significant difference in the N.mikurensis positivity rate was observed a-mong plague foci,habitats,species,and sexes(P＞0.05).Genetic evolution analysis of the groEL gene indicated that the se-quence similarity of nucleic acid sequences in 12 positive samples was 99.5％-100％,and the nucleic acid sequences of N.mikurensis were in the same branch,belonging to cluster Ⅳ.Thus,four species of rodents were found to have low frequency infection with N.mikurensis in Yunnan commensal rodent plague foci.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore whether dexmedetomidine(DEX)can alleviate exertional heatstroke(EHS)-induced rhabdomyolysis(RM)in rats by activating adrenergic α2 receptors,and to explore its potential mechanism based on the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/interleukin-1β(IL-1β)pathway.Methods Thirty-six male Sprague-Dawley(SD)rats,after a 7-day acclimatization training,were randomly divided into six groups:control group(CN group),EHS group,low-dose DEX group(EHS+low DEX group),high-dose DEX group(EHS+high DEX group),DEX combined with yohimbine(YOH)group(EHS+high DEX+YOH group),and YOH group(EHS+YOH),with six rats in each group.Before modeling,EHS+high DEX+YOH group and EHS+YOH group were intraperitoneally injected with YOH at 1 mg/kg,while the other four groups were injected intraperitoneally with an equal dose of physiological saline(0.9%NS).During modeling,except for CN group,the other 5 groups of rats were subjected to heat exercise in a high-temperature and high-humidity chamber to construct an EHS rat model.After successful modeling,EHS+low DEX group was intraperitoneally injected with DEX at 10 μg/kg,EHS+high DEX group and EHS+high DEX+YOH group were intraperitoneally injected with DEX at 30 μg/kg,and CN group,EHS group and DEX+YOH group were intraperitoneally injected with equal doses of saline.After 6 h of observation,all rats were anesthetized,and their blood from the abdominal aorta and gastrocnemius muscle tissue were taken.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β and myoglobin(MB)in rats;biochemical assay kit was used to measure the level of creatine kinase(CK)in rat serum;HE staining was used to observe pathological changes in rat gastrocnemius muscle tissues;transmission electron microscopy was used to observe ultrastructural changes in gastrocnemius muscle;2′,7′-dichlorofluorescent yellow diacetate(DCFH-DA)fluorescent probe was used to detect the level of reactive oxygen species(ROS);and Western blotting was performed to detect the expression levels of NOD-like receptors 3(NLRP3),aspartic protease-1(caspase-1)and adrenergic α2A receptor(ADRA2A).Results Compared with CN group,the levels of serum IL-6,IL-1β,TNF-α,CK and MB in EHS group rats were significantly elevated(P<0.01).HE staining results revealed that the gastrocnemius muscle tissues of rats in EHS group had these pathological manifestations such as disarray of muscle fibrous structure,hemorrhage,edema,and infiltration of inflammatory cells.Transmission electron microscopy results showed that the ultrastructure of the gastrocnemius muscle in EHS group exhibited myofibroblasts with swelling and enlarging in size,cytoplasmic vacuolization,and mitochondria with obvious swelling,degranulation,and disappearance of double cristae.Compared with CN group,the expression levels of ROS,NLRP3,and caspase-1 in gastrocnemius of rats in EHS group significantly increased(P<0.01);Compared with EHS group,the levels of TNF-α,IL-6,IL-1β,CK,MB and the expression levels of ROS,NLRP3,caspase-1 in gastrocnemius tissue of rats in EHS+low DEX group and EHS+high DEX group decreased in a dose-dependent manner(P<0.05),and the pathological damage observed with HE staining and transmission electron microscopy was alleviated by DEX.After YOH pretreatment,compared with the EHS+high DEX group,the serum levels of TNF-α,IL-6,IL-1β,CK,MB and ROS,NLRP3 and caspase-1 in the gastrocnemius muscle tissue of rats in EHS+high DEX+YOH group relatively increased(P<0.05),and the pathological damage observed with HE staining and transmission electron microscopy was exacerbated.The expression of ADRA2A in gastrocnemius muscle of EHS group significantly decreased compared with CN group(P<0.01),and the expression of ADRA2A in muscle of rats in DES+low DEX group and EHS+high DEX group was higher than that in EHS group(P<0.05).Conclusions DEX can alleviate EHS-induced RM by activating ADRA2A,potentially through inhibiting the ROS-dependent NLRP3/IL-1β inflammatory pathway.

Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

The N-end rule pathway is a protein degradation pathway mediated by the ubiquitin-proteasome system, which specifically targets and degrades target proteins by recognizing specific residues at the N-terminus of the proteins. The residues which play a crucial role in the N-end rule pathway are called degrons, also known as N-degrons, as they are usually unstable at the N-terminal end of the protein. Currently, several N-end rule pathways have been identified in the eukaryotes, including the Arg/N-end rule, Ac/N-end rule, and Pro/N-end rule pathways, as well as the recently discovered Gly/N-end rule pathway. The Ac/N-end rule pathway targets proteins containing N-terminal acetylation (Nt-acetylation) residues. The Arg/N-end rule pathway, on the other hand, targets certain unacetylated residues and involves N-terminal arginylation. For proteins with N-terminal proline (Pro) and glycine (Gly) residues, they are neither modified by acetylation nor recognized through the Arg/N-end rule pathway. Therefore, these proteins are primarily recognized and degraded through the Pro/N-end rule pathway and the Gly/N-end rule pathway. The regulation of specific proteins through N-end rule pathway-mediated degradation plays an important role in numerous physiological and pathological processes, such as cardiovascular development, neurogenesis, meiosis, spermatogenesis, HPV infection, and cell apoptosis. In this review, we summarize the role and mechanisms of several known N-end rule pathways and discuss their relationship with certain diseases. As an independent protein degradation system, the N-end rule pathways still hold countless biological secrets waiting for exploring. The comprehensive understanding of these pathways could potentially uncover novel therapeutic targets for various diseases.
Humans ; Proteolysis ; Animals ; Proteasome Endopeptidase Complex/physiology* ; Acetylation ; Proteins/metabolism* ; Protein Processing, Post-Translational ; Ubiquitin/metabolism*

β-Thalassemia caused by abnormal coding of the β-globin gene is the most common hemoglobinopathy in many Asian countries. The in-depth study of the molecular basis and epigenetic mechanism of globin gene expression is the key to explore a new treatment for thalassemia. In this study, FAIRE (formaldehyde-assisted isolation of regulatory elements), 3C (chromosome conformation capture) and ChIP (Chromatin Immunoprecipitation) were used to investigate the three-dimensional interaction network of β-globin family gene loci and the molecular mechanism of functional regulation of gene expression during rapamycin-induced chromatin remodeling in CD4+ T cells. The results showed that the opening degree of globin gene chromatin, the interaction frequency between the gene promoter region and the regulatory element LCR (Locus control regions), and the enrichment efficiency of CTCF (CCCTC-binding factor) in the gene promoter region changed differently during the change of rapamycin treatment concentration from low to high, which led to the same change trend of the gene expression pattern. At the 10 nmol/ L concentration, chromatin accessibility and gene expression decreased (P < 0. 05). At 20 nmol/ L and 50 nmol/ L concentrations, chromatin accessibility increased and gene expression was up-regulated (P < 0. 05). In this study, the molecular mechanism of gene expression regulation of the β-globin family was expounded through this dynamic change process. Our work provides a theoretical and clinical practice basis for clinical precision treatment.

The polymorphism and thermostability of nirmatrelvir, the main antiviral component of the oral COVID-19 treatment drug, were studied. Four polymorphs of nirmatrelvir were prepared by recrystallization methods. Among them, Form 1 and nirmatrelvir methyl tert-butyl ether solvate (Form 2) had been reported in the literature, while nirmatrelvir isobutyl acetate solvate (NMTW-IBAC) and nirmatrelvir ethyl acetate solvate (NMTW-EA) are two new solvates. The crystal structures were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, thermogravimetric analysis and differential scanning calorimetry. The thermostability of polymorphism and crystalline transformation were also investigated by combining Hirshfeld surface analysis and interaction energy analysis. The results showed that nirmatrelvir Form 1 belongs orthorhombic crystal system with the space group P2₁2₁2₁ and one nirmatrelvir molecule included in the asymmetric unit, which has the same crystal structure as nirmatrelvir Form 4 reported in the literature. Owing to its larger thermal expansion, the differences in crystallographic parameters obtained at different temperatures were found between Form 1 and Form 4. Three solvates of nirmatrelvir belonged to the iso-structural with monoclinic crystal system and the space group P2₁, in which the asymmetric unit contains one nirmatrelvir molecule and one solvent molecule. The thermal analysis results showed that nirmatrelvir Form 1 was a solvent-free crystal form with the best thermal stability and the strongest intermolecular hydrogen bonding. Among the three solvates, NMTW-EA has the worst thermal stability and the weakest hydrogen bonding interaction between the nirmatrelvir molecule and the solvent molecule. The energy framework of nirmatrelvir solvates showed that the closer the arrangement between solvent and nirmatrelvir molecules, the greater the total interaction energy between solvent and nirmatrelvir molecules. The phase transition studies of the three solvates showed that NMTW-IBAC and NMTW-EA were transformed into amorphous after desolvation, respectively, while Form 2 undergoes oiling during desolvation. The research provides theoretical guidance for the analysis, identification and quality control of nirmatrelvir polymorphs.