The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.
Animals ; Female ; Humans ; Male ; Mice ; Spermatids/metabolism* ; Spermatogenesis/physiology* ; Spermatozoa/metabolism* ; Thioredoxins/genetics*

Objective： The aim of this study is to explore the predictive value of biparametric magnetic resonance imaging(bpMRI)for pelvic lymph node metastasis in prostate cancer patients with PSA≤20 μg/L and establish a nomogram. Methods： The imaging data and clinical data of 363 patients undergoing radical prostatectomy and pelvic lymph node dissection in the First Affiliated Hospital of Nanjing Medical University from July 2018 to December 2023 were retrospectively analyzed. Univariate analysis and multivariate logistic regression were used to screen independent risk factors for pelvic lymph node metastasis in prostate cancer, and a nomogram of the clinical prediction model was established. Calibration curves were drawn to evaluate the accuracy of the model. Results： Multivariate logistic regression analysis showed extrocapusular extension (OR=8.08,95%CI=2.62－24.97, P<0.01), enlargement of pelvic lymph nodes (OR=4.45,95%CI=1.16－17.11,P=0.030), and biopsy ISUP grade(OR=1.97,95%CI=1.12－3.46, P=0.018)were independent risk factors for pelvic lymph node metastasis. The C-index of the prediction model was 0.834, which indicated that the model had a good prediction ability. The actual value of the model calibration curve and the prediction probability of the model fitted well, indicating that the model had a good accuracy. Further analysis of DCA curve showed that the model had good clinical application value when the risk threshold ranged from 0.05 to 0.70.Conclusion： For prostate cancer patients with PSA≤20 μg/L, bpMRI has a good predictive value for the pelvic lymph node metastasis of prostate cancer with extrocapusular extension, enlargement of pelvic lymph nodes and ISUP grade≥4.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Lymphatic Metastasis ; Retrospective Studies ; Nomograms ; Prostate-Specific Antigen/blood* ; Lymph Nodes/pathology* ; Pelvis ; Predictive Value of Tests ; Prostatectomy ; Lymph Node Excision ; Risk Factors ; Magnetic Resonance Imaging ; Logistic Models ; Middle Aged ; Aged

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides (MOIG) on bone loss of rheumatoid arthritis (RA) rats, and the mechanism of osteoclast function and activity induced by lipopolysaccharide (LPS). RA rats were established by injecting bovin type II collagen. The Bio-ethic Committee of Zhejiang Chinese Medical University approved all experimental protocols associated with this study (IACUC-20180410-03). The collagen-induced arthritis (CIA) rats were administered drug by gavage for 8 weeks; the femoral trabecular micro-structure changes were observed in CIA rats by micro-CT; the LPS-induced osteoclasts model further observed the effect and mechanism of anti-inflammatory osteoporosis in vitro. The results indicated that MOIG could markedly increase bone mineral density (BMD) in CIA rats, improve trabecular micro-structure. In vitro studies demonstrated that MOIG could significantly inhibit osteoclastogensis and differentiation, suppress tartrate resistant acid phosphatase (TRAP) activity, F-actin ring formation, TNF receptor associated factor 6 (TRAF6) recruitment, and inhibitor of nuclear factor kappa-Bα (IκBα) degradation as well as p65 phosphorylation, thereby repressing nuclear factor kappa-B (NF-κB) signaling pathway activation. Subsequently, MOIG effectively inhibited osteoclast nuclear factor of activated T-cells c1 (NFATc1) and cellular oncogene Fos (c-Fos) expression, as well as bone resorption related protein activity including matrix metalloprotein 9 (MMP-9) and cathepsin K (CtsK). Meanwhile, MOIG also repressed the phosphorylation expression of Janus activating kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), thereby inhibiting JAK2/STAT3 signaling pathway activation. Moreover, further studies found that MOIG could suppress glycogen synthase kinase-3β (GSK-3β) activity, and GSK-3β gene silencing could markedly inhibit oetsoclast F-actin ring formation as well as the phosphorylation expression of p65 and STAT3. Of note, compared with GSK-3β gene silencing group, there was no significant difference in the group treated with both MOIG with GSK-3β gene silencing simultaneously. Thus, the results suggested that MOIG may inhibit NF-κB signaling pathway and JAK2/STAT3 signaling pathway activation via regulating GSK-3β, thereby alleviating bone destruction in RA.

Objective To investigate the independent risk factors of comprehensive complication index(CCI)≥26.2 after radical resection of colon cancer,and use these factors to establish and verify a dynamic web-based nomogram model.Methods The clinical data of colon cancer patients who underwent radical resection in the Affiliated Hospital of Jiangnan University from November 2020 to April 2022 were retrospectively collected,and divided into main cohort(November 2020 to October 2021,n=438)and validation cohort(November 2021 to April 2022,n=196).CCI scores of all patients were obtained based on CCI calculator(http://www.assessurgery.com).Univariate and multivariate logistic regression analysis were performed to identify the risk factors for CCI≥26.2,and a nomogram model was constructed.Receiver operator characteristic curve(ROC),C index and calibration curve were used to evaluate the differentiation and consistency of predictive nomogram model,and the decision curve analysis was conducted to assess the clinical benefits of the model.Internal validation of the model is performed in the validation cohort.Results A total of 438 patients were identified in present study,of which 63 cases(14.4%)had CCI≥26.2.Multivariate logistic regression analysis revealed that age≥60 years(OR=2.662,95%CI 1.341-5.285,P=0.005),low third lumbar spine skeletal muscle mass index(L3MI;OR=4.572,95%CI 2.435-8.583,P<0.001),NRS2002≥3(OR=4.281,95%CI 2.304-7.952,P<0.001),and preoperative bowel obstruction(OR=3.785,95%CI 1.971-7.268,P<0.001)were significant independent risk factors for postoperative CCI≥26.2.Based on these results,a static and web-based dynamic nomogram was established(https://jndxfsyywcwksyf.shinyapps.io/DynNomCCI/).The C-index and area under the curve(AUC)of the nomogram were 0.742 and 0.787,respectively.The calibration curve indicated a good consistency between the predicted probability and the actual probability.In the validation cohort,the nomogram also presented good discrimination(C-index=0.722,AUC=0.795)and predictive consistency.The decision curve analysis indicated the clinical benefit and application value of the nomogram prediction model.Conclusion This easy-to-use dynamic nomogram based on 4 independent risk factors can conveniently and reliably predict the probability of CCI≥26.2 after radical resection of colon cancer,which helps optimize the preoperative evaluation system,formulate precise individualized treatment strategies,and enhance recovery after surgery.

Objective:To investigate the combination of internal fixation for periprosthetic fractures of the proximal femur (PFFF) after hip arthroplasty.Methods:The data of 58 patients with periprosthetic fractures after hip arthroplasty from May 2008 to March 2022 were retrospectively analyzed, including 31 males and 27 females. The average age was 75.5±18.2 years (range, 35-95 years). There were 39 total hip arthroplasty and 19 hemiarthroplasty; 37 biological prosthesis and 21 cemented prosthesis. Intraoperative periprosthetic fractures occurred in 6 cases and 52 cases postoperatively. Unified classification system (UCS): UCS IV.3A1 type 2 cases, 3A2 type 1 case, 3B1.1 type 19 cases, 3B2.1 type 25 cases, 3B3 type 2 cases, 3C type 9 cases. Fracture site: 3 cases in zone A (greater trochanter), 46 cases in zone B (around the femoral stem), and 9 cases in zone C (distal to the tip of the femoral stem. Internal fixation is composed of primary and secondary fixation, the main fixation method was the cerclage of steel wire or titanium cable, locking compression plate, and locking attachment plate fixation. The secondary fixation method was the cerclage of titanium cable, which was required to cover three zones A, B and C to form an overall balanced fixation. The modified Harris hip scores (mHHS), plate length, working length and screw number of different internal fixation combinations were compared.Results:The follow-up time was 54.2±21.6 months (range, 11-86 months). All patients showed signs of fracture healing at 10.2±1.5 weeks (range, 7-13 weeks) after operation, and bony union was observed at 19.6±1.3 weeks (range, 17-22 weeks) after operation. No delayed union or nonunion was observed. After operation, one case had a stress fracture and was revised with double-plate internal fixation; one case had a failed internal fixation and was revised with double-plate internal fixation and a large allograft bone graft. The mHHS score of UCSIV.3B2.1 group (80.3±4.6) was the lowest at 6 months after operation, and the difference between the groups of different types was statistically significant ( F=256.72, P<0.001). The score of simple internal fixation group (91.6±4.2) was higher than that of revision combined with internal fixation group (81.9±4.1), and the difference was statistically significant ( t=8.32, P<0.001). The plate length and working length were 24.9±2.5 cm and 12.6±1.7 cm for UCS IV.3B1.1, 25.4±2.6 cm and 13.6±1.8 cm for 3B2.1 and 28.1±2.5 cm and 4.9±1.9 cm for 3C, respectively ( F=5.33, P=0.005; F=6.78, P<0.001). The number of screws in zone A was significant difference among different UCS types ( F=52.67, P<0.001); UCS IV.3B1.1 (6.5±2.3) and 3B2.1 (6.7±2.2) were more than 3B3 (3.5±1.5) and 3C (3.7±1.6). The number of screws in zone B was significant difference among different UCS types ( F=42.15, P<0.001); The number of UCS IV.3B1.1 (2.3±1.6) and 3B2.1 (2.8±1.9) were significantly more than that of 3B3 (1.0±0.5) and 3C (1.2±0.6). The number of screws in zone C was significant differences among different UCS types ( F=39.62, P<0.001); The number of UCS IV.3B1.1 (3.8±1.9) and 3B2.1 (3.9±1.7) were more than that of 3B3 (2.0±0.5), the difference was statistically significant ( P<0.05). Conclusion:The function of hip after simple internal fixation of proximal femoral periprosthetic fractures was better than that of those who underwent revision at the same time; the number of screws of UCSIV.B1 and B2 is more than that of B3.

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) μm to(37.91±0.42) μm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.
Powders ; Solubility ; Technology, Pharmaceutical ; Technology ; Plant Extracts ; Particle Size

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Objective: To investigate the relationship between the levels of selenium, iron and copper in cord blood of neonates and the risk of congenital heart disease (CHD), and analyze their interaction effects. Methods: The subjects were obtained from the birth cohort in Lanzhou area established from 2010 to 2012. A baseline survey was conducted in the first trimester, and the follow-up was conducted in the second trimester, third trimester and 42 days after delivery. The umbilical vein blood was collected from newborns at delivery, and information on their birth outcomes was extracted from medical records. A nested case-control study was used to select 97 neonates with CHD newly diagnosed by echocardiography as the case group, and 194 neonates were selected as the control group by 1∶2 matching according to their mother's age, block and CHD onset time. Inductively coupled ion mass spectrometry was used to detect the concentrations of selenium, iron and copper in neonatal cord blood. The element exposure was categorized into three groups, the low, medium and high concentrations, according to the quartiles Q₁ and Q₃ of selenium, iron and copper concentrations in the control group. The association between cord blood selenium, iron and copper concentrations and CHD was analyzed by conditional logistic regression model using medium concentration as the reference standard. The association of their interactions with CHD was analyzed by a phase multiplication model. Results: The M (Q₁, Q₃) concentration of neonatal cord blood copper was 746.12 (467.48, 759.74) μg/L in the case group and 535.69 (425.21, 587.79) μg/L in the control group, with a statistically significant difference between the two groups (P<0.05). After adjustment for confounders, logistic regression models showed that the risk of CHD development was increased in neonates with either high copper in cord blood (OR=4.062, 95%CI: 2.013-8.199) or high copper combined with high iron (OR=3.226, 95%CI: 1.343-7.750). No correlation was observed between selenium and iron concentrations and the development of CHD in neonates. There was a multiplicative interaction between copper and iron in cord blood on the risk of developing CHD (OR=1.303, 95%CI: 1.056-1.608). Conclusion: There is a multiplicative interaction between iron and copper elements. The high copper and the high copper combined with high iron in umbilical cord blood are risk factors for neonatal CHD.
Humans ; Infant, Newborn ; Copper/analysis* ; Selenium ; Iron/analysis* ; Fetal Blood/chemistry* ; Case-Control Studies ; Heart Defects, Congenital

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.
Female ; Humans ; Animals ; Rats ; Acetic Acid ; Curcuma ; Dysmenorrhea ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha ; Cyclooxygenase 2