ObjectiveTo decipher the mechanism by which Zuoguiwan （ZGW） treat hyperthyroidism in rats with kidney-Yin deficiency based on the dopamine receptor D4 （DRD4）/nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4） signaling pathway. MethodsThe rat model of kidney-Yin deficiency was induced by unilateral intramuscular injection of dexamethasone （0.35 mg·kg^-1）. After successful modeling， the rats were randomized into model， methimazole （positive control， 5 mg·kg^-1）， low-， medium-， and high-dose （1.85， 3.70， 7.40 g·kg^-1， respectively） ZGW， and normal control groups. After 21 days of continuous gavage， the behavioral indexes and body weight changes of rats were evaluated. The pathological changes of the renal tissue were observed by hematoxylin-eosin staining. The serum levels of thyroid hormones ［triiodothyronine （T₃）， thyroxine （T₄）， thyroid-stimulating hormone （TSH）］， renal function indexes ［serum creatine （Scr） and blood urea nitrogen （BUN）］， energy metabolism markers ［cyclic adenosine monophosphate （cAMP） and cyclic guanosine monophosphate （cGMP）］， and oxidative stress-related factors ［superoxide dismutase （SOD）， malondialdehyde （MDA）， and NADPH）］ were measured by enzyme-linked immunosorbent assay （ELISA）. Western blot was employed to analyze the expression of DRD4， NOX4， mitochondrial respiratory chain complex proteins ［NADH：ubiquinone oxidoreductase subunit S4 （NDUFS4） and cytochrome C oxidase subunit 4 （COX4）］， and inflammation-related protein ［tumor necrosis factor-alpha （TNF-α）， interleukin-6 （IL-6）， p38 mitogen-activated protein kinase （MAPK）］ pathway in the renal tissue. ResultsCompared with the normal group， the model group showed mental malaise， body weight decreases （P<0.01）， inflammatory cell infiltration in the renal tissue， a few residual parotid glands in the thyroid， elevations in serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA， and NADPH （P<0.01）， down-regulation in protein levels of TSH， SOD， and DRD4 （P<0.05， P<0.01）， and up-regulation in expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.01）. Compared with the model group， ZGW increased the body weight （P<0.05， P<0.01）， reduced the infiltration of renal interstitial inflammatory cells， restored the thyroid structure and follicle size， lowered the serum levels of T₃， T₄， Scr， BUN， cAMP， cAMP/cGMP， MDA and NADPH （P<0.05， P<0.01）， up-regulated the expression of TSH， SOD and DRD4 （P<0.05， P<0.01）， and down-regulated the expression of NOX4， p-p38 MAPK/p38 MAPK， and inflammatory factors （P<0.05， P<0.01）. Moreover， high-dose ZGW outperformed methimazole （P<0.05）. ConclusionBy activating DRD4， ZGW can inhibit the expression of NOX4 mediated by the p38 MAPK pathway， reduce oxidative stress and inflammatory response， thereby ameliorating the pathological state of hyperthyroidism due to kidney-Yin deficiency. This study provides new molecular mechanism support for the clinical application of ZGW.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Objective To investigate the role of the ubiquitin specific protease 22(USP22)/lysine specific demethylase 3A(KDM3A)pathway in improving ischemia-reperfusion injury of hypoxic cardiomyocytes in sevoflurane postconditioning(SPC).Methods H9c2 rat cardiomyocytes were divided into control group,hypoxia/reoxygenation(H/R)group,H/R+sevoflurane(Sevo)group,H/R+Sevo+si-NC group,H/R+Sevo+si-USP22 group and H/R+Sevo+si-KDM3A group.Real time fluorescence quantitative PCR(qRT-PCR)and Western blotting were used to detect the mRNA and protein expression of USP22 and KDM3A,cell activity was detected by cell counting kit-8,apoptosis rate was detected by flow cytometry,and ELISA was used to detect the levels of creatine kinase MB(CK-MB)and cardiac troponin I(cTn I),while the assay kit was used to detect the levels of lactate dehydrogenase(LDH).Immunoprecipitation assay was used to detect the interaction between USP22 and KDM3A proteins,as well as KDM3A ubiquitination.Results Compared with the control group,the mRNA and protein expression of USP22 in H/R group cells decreased(t=49.574,14.852),cell activity decreased(t=46.597),cell apoptosis rate,CK-MB,cTn I and LDH levels increased(t=17.722,21.346,22.863,9.722),KDM3A protein expression decreased(t=15.879),and ubiquitination level increased,the differences were statistically significant(all P<0.01).Compared with the H/R group,the mRNA and protein expression of USP22 in H9c2 cells in the H/R+Sevo group increased(t=24.648,17.644),cell activity increased(t=44.703),apoptosis rate,CK-MB,cTn I and LDH levels decreased(t=13.736,18.018,17.012,13.856),KDM3A protein expression increased(t=12.970),ubiquitination level decreased,and the differences were statistically significant(all P<0.01).Compared with the H/R+Sevo+si-NC group,the cell viability of the H/R+Sevo+si-USP22 group was decreased(t=20.785),the apoptosis rate,CK-MB,cTn I and LDH levels were increased(t=6.821,6.862,6.442,3.781),the KDM3A protein expression was decreased(t=4.648),and the ubiquitination level was increased,and the differences were statistically significant(all P<0.05).USP22 was enriched in the promoter of KDM3A,and there was a direct regulatory relationship between USP22 and KDM3A.Compared with the H/R+Sevo+si-NC group,the cell viability was decreased(t=16.501),the apoptosis rate and the levels of CK-MB,cTn I and LDH were increased in the H/R+Sevo+si-KDM3A group(t=8.954,10.533 6.801,8.004),and the differences were statistically significant(all P<0.01).Conclusion SPC attenuates H/R-induced H9c2 cardiomyocyte injury,and the mechanism may be related to the up-regulation of USP22 stabilizing KDM3A protein levels.

Objective To explore the clinical characteristics as well as molecular epidemiological features of resis-tance genes and virulence genes of carbapenem-resistant Klebsiella pneumoniae(CRKP)infection in a region,and provide scientific basis for the prevention,treatment,and epidemiological study of CRKP.Methods 60 non-repeti-tive CRKP strains isolated clinically from Puyang Oilfield General Hospital from November 2023 to September 2024 were analyzed retrospectively.Antimicrobial susceptibility testing was performed using VITEK 2 Compact automa-tic microbial analyzer,K-B disk diffusion method,and micro-broth dilution method.Mucus phenotype of bacterial strains was identified by string test.Carbapenemase was detected by carbapenemase inhibitor enhancement assay.Molecular features,such as multi-locus sequence typing(MLST),capsule serotypes,resistance genes,virulence genes,plasmid replication types of strains,as well as the genetic and evolutionary relationships of strains were de-termined by whole genome sequencing and bioinformatics analysis.Results CRKP strains were mainly isolated from elderly male hospitalized patients.Specimens were mostly from sputum(71.67％),mainly distributed in depart-ment of respiratory medicine(30.00％).All strains were highly resistant to multiple commonly used antimicrobial agents,only with high susceptibility rates to cefotaxime/avibactam,tigecycline,and polymyxin B(＞60.00％).Two CRKP strains were positive for string test.95.00％of the strains produced class A serine carbapenemase.All strains carried fluoroquinolone,phosphomycin,β-lactam,and aminoglycoside resistance genes;enterobactin,Esche-richia coli common pilus(ECP),and outer membrane protein-related virulence genes;as well as plasmids from the IncF plasmid family.Carbapenemase gene was mainly blaKPC-2(95.00％),and the major capsule serotype was KL19(43.33％).In MLST,ST11(51.67％)was the dominant clone group,and ST11-KL62(n=12)was the dominant subtype.Conclusion CRKP in this hospital is highly resistant to multiple commonly used antimicrobial agents,and its mechanism of resistance to carbapenems is mainly related to the presence of blaKPC-2 resistance gene.All strains have coexisting multiple resistance genes and virulence genes,and show a phenomenon of multi-clone transmission.ST11 is the dominant clone group,and ST11-KL62 is the main prevalent subclone type.

Objective:To compare the efficacy of active warming versus conventional warming during the perioperative period of robotic-assisted total hip arthroplasty (THA) for femoral neck fracture in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 312 elderly patients with femoral neck fracture who underwent robot-assisted THA at Second Affiliated Hospital of Xi ′an Jiaotong University from January 2024 to January 2025, including 196 males and 116 females, aged 65-89 years [(77.0±7.3)years]. Among them, 156 patients received standardized thermal management (active warming group), involving the administration of pre-warmed intravenous fluids and use of an inflatable warming blanket preoperatively, combined application of a forced-air warming system and warmed fluids intraoperatively, and transfer to a temperature-controlled ward combined with a foot circulatory compression device postoperatively. The other 156 patients received conventional warming with cotton quilts (conventional warming group), involving no administration of pre-warmed intravenous fluids preoperatively, use of warmed fluids intraoperatively, and transfer to a standard ward without the use of a foot circulatory compression device postoperatively. Core body temperature was compared between the two groups at 30 minutes preoperatively, 30 minutes intraoperatively, immediately postoperatively, and at 1 hour, 1 day, 5 days, and 7 days postoperatively. Changes in the coagulation function, including prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and the inflammatory marker C-reactive protein (CRP) were assessed at 1 day preoperatively and at 1, 5, and 7 days postoperatively. Length of hospital stay and incidence of postoperative complications (incision infection, deep vein thrombosis, cardiac complications, and unplanned reoperations) were also recorded. Results:The core body temperature at 30 minutes intraoperatively, immediately postoperatively and at 1 hour postoperatively was (36.77±0.17)℃, (36.29±0.14)℃, and (36.35±0.14)℃ in the active warming group, significantly higher than (36.12±0.27)℃, (35.49±0.25)℃, and (35.67±0.29)℃ in the conventional warming group ( P<0.01). No significant differences in body temperature were observed between the two groups at 30 minutes preoperatively, at 1, 5, or 7 days postoperatively ( P>0.05). At 1 day postoperatively, the PT, TT and APTT were (8.5±1.3)seconds, (10.0±0.9)seconds and (24.8±2.3)seconds, significantly lower than (9.7±1.3)seconds, (12.1±1.5)seconds and (29.2±2.7)seconds in the conventional warming group ( P<0.01). There were no significant differences in PT, TT, APTT or CRP levels between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The CRP level at 1 day postoperatively was (8.0±3.0)mg/L in the active warming group, significantly lower than (13.5±3.2)mg/L in the conventional warming group ( P<0.05). There were no significant differences in CRP between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The average length of hospital stay was (12.2±1.4)days in the active warming group, significantly shorter than (14.9±1.4)days in the conventional warming group ( P<0.01). The perioperative complication rate was 6.4% (10/156) in the active warming group, significantly lower than 17.9% (28/156) in the conventional warming group ( P<0.01). Conclusion:For elderly patients with femoral neck fracture operated via robot-assisted THA, active warming during the perioperative period can more effectively maintain intraoperative normothermia, improve early postoperative coagulation function, reduce inflammatory response, shorten the length of hospital stay, and decrease complication rate when compared with conventional warming.

Objective:To investigate the temporal and spatial distribution characteristics of fluoride in drinking water in rural areas of Shaanxi Province.Methods:From April 2019 to September 2023, rural drinking water monitoring sites were set up in all 108 agriculture-related counties (cities and districts) in Shaanxi Province. The ex-factory water and tap water were collected annually in dry season and wet season for water fluoride determination and water fluoride exceeding standard evaluation, and the exceedance rates of water fluoride were compared according to different years, regions, water period types, water sample types, water source types, and water treatment methods.Results:A total of 31 221 water samples were collected in Shaanxi Province from 2019 to 2023, and the median water fluoride was 0.370 mg/L, ranging from 0.001 to 6.220 mg/L. The exceedance rates of water fluoride in each year were 5.93% (370/6 236), 3.21% (200/6 232), 3.05% (191/6 260), 3.64% (228/6 256), and 2.36% (147/6 237), respectively. The differences between different years were statistically significant (χ 2 = 132.31, P < 0.001). The exceedance rates of water fluoride in Guanzhong, Northern Shaanxi, and Southern Shaanxi were 5.10% (563/11 044), 5.93% (376/6 339), and 1.42% (197/13 838), respectively, with statistically significant differences between different regions (χ 2 = 355.76, P < 0.001). The exceedance rates of water fluoride during the dry season and wet season were 3.68% (574/15 615) and 3.60% (562/15 606), respectively, with no statistically significant difference between the two water periods (χ 2 = 0.12, P = 0.724). The fluoride exceedance rates of ex-factory water and tap water were 3.15% (442/14 024) and 4.04% (694/17 197), respectively. The fluoride exceedance rate of tap water was higher than that of ex-factory water, and the difference was statistically significant (χ 2 = 17.21, P < 0.001). The fluoride exceedance rates of surface water and groundwater were 0.37% (39/10 588) and 5.32% (1 097/20 633), respectively. The fluoride exceedance rate of groundwater was higher than that of surface water, and the difference was statistically significant (χ 2 = 488.68, P < 0.001). The fluoride exceedance rates of conventional treatment, sedimentation and filtration, disinfection only, and untreated water samples were 1.21% (111/9 174), 2.82% (130/4 604), 3.56% (309/8 686), and 6.69% (586/8 757), respectively. There was a statistically significant difference between different water treatment methods (χ 2 = 396.04, P < 0.001). Conclusions:The fluoride exceedance rate of drinking water in rural areas of Shaanxi Province has decreased from 2019 to 2023, and the exceedance water samples are mainly concentrated in Northern Shaanxi and Guanzhong regions. There are differences in the fluoride exceedance rate of water samples in different years, regions, water sample types, water source types, and water treatment methods.

Objective:To investigate the iodine nutrition status of children and pregnant women in different water iodine areas of Shandong Province.Methods:From February to September 2023, Leling City (iodine deficient), Gaotang County (moderate iodine), and Liangshan County (high iodine) in different water iodine areas of Shandong Province were selected as survey sites. One village was selected from each county (city) in five directions: east, west, south, north, and center. Forty children aged 8 to 10 years (balanced in age, half male and half female) and 20 pregnant women were selected as survey subjects in each village. Random urine samples of children and pregnant women were collected to test for urinary iodine. Meanwhile, thyroid examinations were conducted on children to calculate the goiter rate.Results:A total of 600 urine samples of children were tested, with a median urinary iodine level of 246.0 μg/L. The median urinary iodine levels of children in iodine deficient, moderate iodine and high iodine areas were 219.6, 208.0 and 446.0 μg/L, respectively ( n = 200, 200, 200). The median urinary iodine level of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 600 children underwent thyroid examinations, with a goiter rate of 5.8% (35/600). The goiter rate of children in iodine deficient, moderate iodine, and high iodine areas were 4.0% (8/200), 1.0% (2/200), and 12.5% (25/200), respectively. The goiter rate of children in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas ( P < 0.05). A total of 247 urine samples of pregnant women were tested, with a median urinary iodine level of 158.2 μg/L. The median urinary iodine levels of pregnant women in iodine deficient, moderate iodine, and high iodine areas were 75.3, 175.2 and 321.2 μg/L, respectively ( n = 98, 84, 65). The median urinary iodine level of pregnant women in high iodine area was significantly higher than that in iodine deficient and moderate iodine areas, and the median urinary iodine level of pregnant women in moderate iodine area was significantly higher than that in iodine deficient area ( P < 0.05). Conclusion:The urinary iodine levels of children and pregnant women and the goiter rate of children in high iodine area of Shandong Province are significantly increased, and water iodine may be a key factor affecting the iodine nutrition status of the population.

The differences in chemical quality characteristics between Xinjiang Rehmannia glutinosa and R. glutinosa were analyzed to provide a theoretical basis for the introduction and quality control of R. glutinosa. In this study, the high performance liquid chromatography(HPLC) fingerprints of 6 batches of Xinjiang R. glutinosa and 10 batches of R. glutinosa samples were established. The content of iridoid glycosides, phenylethanoid glycosides, monosaccharides, oligosaccharides, and polysaccharides in Xinjiang R. glutinosa and R. glutinosa was determined by high performance liquid chromatography-diode array detection(HPLC-DAD), high performance liquid chromatography-evaporative light scattering detection(HPLC-ELSD), and ultraviolet-visible spectroscopy(UV-Vis). The determination results were analyzed with by chemical pattern recognition and entropy weight TOPSIS method. The results showed that there were 19 common peaks in the HPLC fingerprints of the 16 batches of R. glutinosa, and catalpol, aucubin, rehmannioside D, rehmannioside A, hydroxytyrosol, leonuride, salidroside, cistanoside A, and verbascoside were identified. Hierarchical cluster analysis(HCA) and principal component analysis(PCA) showed that Qinyang R. glutinosa, Mengzhou R. glutinosa, and Xinjiang R. glutinosa were grouped into three different categories, and eight common components causing the chemical quality difference between Xinjiang R. glutinosa and R. glutinosa in Mengzhou and Qinyang of Henan province were screened out by orthogonal partial least squares discriminant analysis(OPLS-DA). The results of content determination showed that there were glucose, sucrose, raffinose, stachyose, polysaccharides, and nine glycosides in Xinjiang R. glutinosa and R. glutinosa samples, and the content of catalpol, rehmannioside A, leonuride, cistanoside A, verbascoside, sucrose, and glucose was significantly different between Xinjiang R. glutinosa and R. glutinosa. The analysis with entropy weight TOPSIS method showed that the comprehensive quality of R. glutinosa in Mengzhou and Qinyang of Henan province was better than that of Xinjiang R. glutinosa. In conclusion, the types of main chemical components of R. glutinosa and Xinjiang R. glutinosa were the same, but their content was different. The chemical quality of R. glutinosa was better than Xinjiang R. glutinosa, and other components in R. glutinosa from two producing areas and their effects need further study.
Rehmannia/classification* ; Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Quality Control

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

ObjectiveTo explore the effectiveness of feedforward control mode on improving occupational burnout among operating room nurses through theoretical research and clinical practice， with a view to promoting their physical and mental health and enhancing the quality of surgical nursing. MethodsA total of 440 operating room nurses from different regions， scales， and nursing experiences in Shaanxi Province from November 2023 to December 2023 were randomly divided into an experimental group and a control group， with 220 nurses in each group. While the control group received routine intervention measures， the experimental group introduced a feedforward control mode based on the control group， with “emotional exhaustion，” “depersonalization，”and“personal achievement” as observation indicators. ResultsThe incidence of occupational burnout in the experimental group was 11.4%， while that in the control group was 20.0%. The experimental group showed a significantly lower incidence than the control group （P=0.013）. ConclusionThe feedforward control mode can significantly alleviate nurses’ sense of job burnout， promote the improvement of surgical nursing quality， as well as continuously improve the scientific rigor， advancement， and humanistic nature of nursing services， which is conducive to building a harmonious and efficient nursing team. The spirit of teamwork， reflected in mutual support， mutual trust， and joint efforts for surgical success and patient health， has become an important component of nurses’ professional ethics.