Objective: To investigate the precise detection methods for weak partial D type 15 and evaluate their implications for blood transfusion safety, along with the development of corresponding strategies. Methods: A combination of serological methods, including the microplate method, indirect antiglobulin tube method, and microcolumn gel card method, was employed to identify RhD-negative and RhD variant samples. RhD-negative samples were screened for the presence of RHD genes using whole-blood direct PCR amplification. Subsequently, RhD variant samples and RhD-negative samples containing RHD genes underwent full-coding-region sequencing of the RHD gene to confirm their genotypes. The genotyping results were further correlated with the serological test findings for comprehensive analysis. Results: Among 615 549 first-time healthy blood donors, 3 401 samples with an RhD-negative phenotype and 156 samples with RhD variant were identified. Of the 3 401 RhD-negative samples, 1 054 were found to harbor RHD genes. Gene sequencing analysis of the 156 RhD variants and the 1 054 serological negative samples revealed that 89 samples contained the RHD 15 (c. 845G>A) allele. Conclusion: The integration of serological testing methods and genotyping technologies for the precise determination of RhD blood type plays a critical role in ensuring the safety and compatibility of blood transfusions.

Objective:To evaluate the role of ubiquitin-specific peptidase 22 (USP22) in myocardial ischemia-reperfusion (I/R) injury in diabetic mice.Methods:Seventy-eight SPF male C57BL/6 mice, aged 6-8 weeks, were divided into 6 groups using a random number table method: sham operation group (Sham group, n=12), type 1 diabetes mellitus + sham operation group (T1D+ Sham group, n=12), myocardial I/R injury group (I/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury group (DI/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury + empty vector group (DI/R+ V group, n=15), and type 1 diabetes mellitus + myocardial I/R injury + USP22 overexpression group (DI/R+ U group, n=15). Type 1 diabetes mellitus was induced by intraperitoneal injection of streptozotocin-citrate buffer. Myocardial I/R was induced by ligation of the left coronary artery. At 1 day before developing the myocardial I/R injury model, DI/R+ U group and DI/R+ V group received an intramyocardial injection of USP22 overexpression plasmid or empty vector plasmid, respectively. At 24 h of reperfusion, cardiac function was assessed using the echocardiography to measure the left ventricular ejection fraction and left ventricular fractional shortening. The mice were then sacrificed, and their hearts were harvested for measurement of the myocardial infarct size, for microscopic examination of pathological changes (using HE staining) and for determination of the apoptosis rate (TUNEL staining), reactive oxygen species(ROS) activity (DHE staining), and USP22 expression (by Western blot, immunofluorescence, and immunohistochemistry). Proteomic analysis was performed to identify downstream proteins regulated by USP22, and protein-protein interactions were investigated using co-immunoprecipitation. Results:Compared with Sham group, the cardiac function indices were significantly decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct size was significantly increased, the cardiac function indices were decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was aggravated in DI/R group. Compared with DI/R+ V group, the percentage of myocardial infarct size was significantly decreased, the cardiac function indices were increased, the apoptosis rate of myocardial cells and ROS activity were decreased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was alleviated in DI/R+ U group. The results of proteomics combined with co-immunoprecipitation experiments showed an interaction between calponin 1 and USP22. Conclusions:During myocardial I/R injury in diabetic mice, USP22 may act as an endogenous protective mechanism, and calponin 1 might be a downstream mechanism through which USP22 exerts its protective effects.

Objective:To explore the application value and treatment effects of multiple free anterolateral perforator flaps of calf for reconstruction of multiple digital wounds in single hand.Methods:From August 2020 to March 2022, 12 patients with soft tissue defects in 35 digits were treated in Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Ten patients were male and 2 were female, aged 25 to 58 years old. Of the patients, 1 had soft tissue defects in 5 digits, 3 in 4 digits, 2 in 3 digits and 6 in 2 digits. The size of defects was from 1.2 cm ×1.2 cm to 7.0 cm×3.5 cm after debridement. The vascular perforators discovered from intraoperative explorations were found originating from the superficial peroneal artery in 24 flaps, from the peroneal artery in 7 flaps and from the anterior tibial artery in 4 flaps. During surgery, the perforator artery and accompanying veins of the flaps were anastomosed with the proper digital artery and palmar or dorsal subcutaneous veins in the recipient site, respectively. The size of the flaps was from 1.5 cm×1.5 cm to 7.5 cm×4.0 cm. No nerve was affected in the surgery. The wound at donor sites in the calf was sutured directly. Regular postoperative follow-ups were conducted at outpatient clinics. The comprehensive evaluation scale of flap was used to assess the conditions of the donor and recipient sites.Results:In this study, all 35 soft tissue defects of digits in 12 patients were reconstructed by the anterolateral perforator flaps of calf. All the 35 flaps survived after surgery, with a 100% of survival rate. The patients were instructed to carry out early functional training after surgery. Follow-up lasted 6 to 24 months, with an average of 11 months. Twenty-five flaps were found in slightly swollen, and further flap thinning surgery were carried out 3 months after the primary surgery, while the rest of the flaps had good appearance and texture. At 6 months after surgery, all flaps recovered a partial deep and shallow sensory and sense of touch. All wound at donor sites in calf had one-stage healing without dysfunction. The comprehensive evaluation scale was excellent in 28 flaps and good in 7 flaps. The excellent and good rate was 100%.Conclusion:It is an effective method to use multiple free anterolateral perforator flaps of calf to reconstruct multiple digit defects in single hand. The flaps can be conveniently harvested and the multiple digital defects in single hand can be reconstructed in primary surgery with small damages to the donor sites and together with satisfactory clinical outcomes.

Noncarious lesions,a multifactorial condition encompassing tooth attrition,abrasion,and erosion,have a surge in prevalence and required increased attention in clinical practice.These nonbacterial-associated tooth de-fects can compromise aesthetics,phonetics,and mastica-tory functions.When providing full-arch fixed occlusal rehabilitation for such cases,the treatment strategy should extend beyond by restoring dentition morphology and aesthetics.This report details a complex case of erosive dental wear addressed through a fully digital,full-arch fixed occlusal rehabilitation.A 4D virtual patient was created using multiple digital data sources,including intraoral scanning,3D facial scanning,digital facebow registration,and mandibular movement tracing.With a comprehensive understanding of the masticatory system,various types of microinvasive prostheses were customized for each tooth,including labial ve-neers,buccal-occlusal veneers,occlusal veneers,overlays,inlays,and full crowns,were customized for each tooth.The reported digital workflow offered a predictable diagnostic and treatment strategy,which was facilitated by virtual visual-ization and comprehensive quality control throughout the process.

Objective To investigate the application value of point-of-care lung ultrasound (POC-LUS) scoring in selecting respiratory support treatment modalities for neonatal infectious pneumonia (NIP). Methods A total of 89 NIP patients were selected as the study subjects and divided into control group (no assisted ventilation) with 46 cases, noninvasive group (noninvasive assisted ventilation) with 28 cases, and invasive group (invasive mechanical ventilation) with 15 cases based on the degree of dyspnea and blood gas analysis results. The POC-LUS scores of the three groups were compared, and the correlations of POC-LUS scores with arterial oxygen partial pressure [p_a(O₂)] and arterial carbon dioxide partial pressure [p_a(CO₂)] were analyzed. Receiver operating characteristic (ROC) curves were plotted to assess the predictive efficacy of POC-LUS scores for the need for noninvasive assisted ventilation or invasive mechanical ventilation in NIP patients. Results The POC-LUS scores of the noninvasive group and the invasive group were (31.7±7.3) and (42.1±8.0), respectively, which were higher than (21.5±7.3) of the control group. Additionally, the score of the invasive group was higher than that of the noninvasive group (P < 0.05). Correlation analysis revealed a significant negative correlation between POC-LUS scores and p_a(O₂) (r=-0.802, P < 0.05), and a significant positive correlation with p_a(CO₂) (r=0.807, P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of POC-LUS scores for predicting the need for noninvasive assisted ventilation and invasive mechanical ventilation were 0.918 (95%CI, 0.862 to 0.973) and 0.938 (95%CI, 0.889 to 0.987), respectively. The sensitivity was 0.767 and 0.933, and the specificity was 0.935 and 0.824, with optimal cutoff values of 29.5 and 31.5, respectively. Conclusion POC-LUS scoring can quantitatively assess the severity of lung lesions in NIP patients and serves as a guiding tool for clinicians in selecting assisted ventilation treatment modalities.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

Objective:To explore the oxidative stress of cerebral white matter lesion (WML) and normal-appearing white matter (NAWM) with in vivo proton exchange rate (k ex) MRI on relapse-remitting multiple sclerosis (RRMS) patients. Methods:Clinical and imaging data of 37 patients (case group) with RRMS patients of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology were analyzed retrospectively from November 2018 to November 2021, including 11 males and 26 females aged 18-41 (29±7) years. Another 22 age-matched healthy volunteers (control group) were recruited for the same period, including 4 males and 18 females aged 23-44 years with a median age of 25 (24, 28.25) years. All subjects received conventional MR protocols and chemical exchange saturation transfer imaging. The manifestation of WML on the k ex map and T 1WI images were assessed while the k ex values of WML, NAWM and normal white matter (NWM) of control group were quantitatively evaluated. Student′s t test was used to compare the k ex difference of WML and NAWM in the case group, NAWM in the case group and NWM in the control group, low-signal and isosignal WML in T 1WI. Spearman rank correlation was used to analyze the correlation of the k ex values of WML with patients′ expanded disability status scale (EDSS) score. Results:A total of 272 WML were found in the 37 RRMS patients, and 25.4% (69/272) were T 1-hypointense. The k ex value of WML in the case group [(932±108) s -1] was higher than that of NAWM [(771±26) s -1], and the difference was statistically significant ( t=8.95, P<0.001); the k ex value of NAWM in the case group [(771±26) s -1 ] was higher than that of NWM [(745±26) s -1] in the control group, and the difference was statistically significant ( t=3.96, P<0.001). The k ex value [(1 039±110) s -1] of WML with low signal at T 1WI was higher than that of WML with equal signal [(895±79) s -1], with a statistically significant difference ( t=9.78, P<0.001). Correlation analysis showed that the k ex value of WML in the case group was positively correlated with the EDSS score ( r=0.54, P<0.001). Conclusions:The elevated k ex values of WML and NAWM reflect the cerebral oxidative stress of RRMS patients and are positively correlated to the severity of tissue damage, which suggests the role of oxidative stress in RRMS lesion formation and brain atrophy.

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

BACKGROUND: Hyaluronic acid dermal fillers are composed of cross-linked viscoelastic particles with high biocompatibility. The performance of the fillers is determined by the viscoelastic properties of particles and the connecting force between particles. However, the relationships among the properties of fillers, the interaction of the gels and the surrounding tissue are not clear enough.METHOD: Four kinds of typical dermal filler were selected in this research to reveal the interaction between the gels and cells. A series of analytical tools was applied to characterize the structure and physicochemical properties of the gel, as well as observing their interaction with the surrounding tissues in vivo and discussing their internal mechanism.RESULT: The large particles internal the gel and the high rheological properties endow the Restylane2 with excellent support. However, these large-size particles have a significant impact on the metabolism of the local tissue surrounding the gel. Juvéderm3 present gel integrity with the high cohesiveness and superior support. The rational matching of large and small particles provides the Juvéderm3 with supporting capacity and excellent biological performance. Ifresh is characterized by small-size particles, moderate cohesiveness, good integrity, lower viscoelasticity and the superior cellular activity located the surrounding tissues. Cryohyaluron has high cohesion and medium particle size and it is prominent in cell behaviors involving localized tissues. Specific macroporous structure in the gel may facilitate the nutrients delivering and removing the waste. CONCLUSION It’s necessary to make the filler both sufficient support and biocompatibility through the rational matching of particle sizes and rheological properties. Gels with macroporous structured particle showed an advantage in this area by providing a space inside the particle.