Objective: To establish a method for the genotyping of fetal M blood group antigen by extracting cell-free fetal DNA (cff-DNA) from maternal plasma, so as to guide the management of M antigen-negative pregnant women with IgG anti-M antibody during pregnancy. Methods: A realtime fluorescent quantitative PCR (realtime PCR) method was established. The specificity and sensitivity of the method were validated by dilution of genomic DNA. Subsequently, a total of 12 M antigen-negative pregnant women were enrolled. The cff-DNA was extracted from maternal plasma, and fetal M antigen genotyping was performed by realtime PCR. Fetuses were classified as M-positive or M-negative according to the presence or absence of amplification curve. The accuracy of the method was validated by comparing fetal M antigen genotyping results with the serological results using the cord or peripheral blood of the neonate at birth. Results: Among the 12 M antigen-negative pregnant women, anti-M was detected in five cases, of which four cases had IgG anti-M, and one case had fetal anemia. The results of fetal M antigen genotyping showed that 9 cases were M-positive (9/12, 75%) and 3 cases were M-negative (3/12, 25%). Serological results of blood samples collected after birth from four M-positive fetuses and one M-negative fetus were consistent with the genotyping results. Conclusion: We have, for the first time, established a non-invasive prenatal genotyping method for fetal M antigen using maternal plasma cff-DNA, and preliminarily demonstrated the feasibility of this method.

This paper summarizes Professor LU Fang's clinical experience in treating systemic lupus erythematosus （SLE） based on the differentiation and treatment of heat-toxin and blood-stasis in the collaterals. SLE is generally characterized by deficiency in origin with excess in manifestation. The core pathogenesis is heat-toxin obstructing the collaterals. During the acute active stage， the predominant pattern is blazing heat-toxin causing blood stasis， while in the chronic remitting stage， the main pattern is toxic stasis blocking the collaterals with qi and yin deficiency. Clinical treatment follows the basic principle that treat with salty-cold herbs， when heat invades internally and that assist with acrid-dispersing herbs when stasis obstructs the collaterals. The self-formulated Yimian Decoction （抑免汤） serves as the base formula and is applied in stages. During the acute active stage， it is often combined with herbs for clearing heat and detoxifying， cooling blood and resolving stasis， and unblocking the collaterals. In the chronic remitting stage， it is often combined with herbs for activating blood circulation and unblocking the collaterals， as well as tonifying qi and nourishing yin.

Objective: To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools. Methods: Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test. Results: Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05). Conclusions In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.

Objective: To investigate the association between different digital media usage types and depressive symptoms among junior and senior high school students, so as to provide a scientific reference for making precise mental health prevention and intervention strategies for adolescents. Methods: In October 2024, a convenience cluster sample of 3 225 students was collected from 2 junior high schools and 2 senior high schools in Shenyang City. Participants were investigated for its daily usage duration of various digital media types and depressive symptoms. Cochran-Armitage trend test was used to examine trend in depressive symptom detection rates across digital media usage types. Multivariate Logistic regression model was employed to assess associations, with stratified analyses by gender and educational stage. Results: The daily usage durations for educational/learning, social/chatting, gaming, and video/music/novel digital media were 30.0(12.1, 60.0), 22.9(9.3, 50.0), 17.1(0.0, 50.0), and 22.9(8.6, 55.7) minutes for junior and senior high school students, respectively. The detection rate of depressive symptoms was 46.1%. Among them, the detection rate of depressive symptoms of girls (49.8%) was higher than that of boys (42.3%), and that of senior high school students (53.2%) was higher than that of junior high school students (39.7%), and the differences were statistically significant ( χ 2= 18.35, 59.02, both P <0.01). Cochran-Armitage trend test revealed significant upward trends in depressive symptom detection rates with increasing usage of non educational digital media (social/chatting: Z =4.77; gaming: Z =3.24; video/music/novel: Z =7.30, all P <0.01). Logistic regression analysis showed that, compared to usage <1 h/d, using social/chatting digital media for 1-<2 h/d ( OR =1.66), 2-<3 h/d ( OR =1.80), and ≥3 h/d ( OR =2.68), gaming for 1-<2 h/d ( OR =1.48), 2-<3 h/d ( OR =1.90), and ≥3 h/d ( OR =2.93), and video/music/novel for 1-<2 h/d ( OR =1.76), 2-<3 h/d ( OR =2.00), and ≥3 h/d ( OR = 3.48) were all significantly associated with increased risks of depressive symptoms (all P <0.01). Conclusions Excessive use of non-educational digital media is a risk factor for depressive symptoms in adolescents. Regulating usage duration is beneficial for promoting adolescent mental health.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective: To explore the correlation and lag effects of environmental factors on pediatric respiratory disease visits at hospital, so as to provide scientific basis for disease prediction and optimizing clinical diagnosis and treatment. Methods: Data from 503 889 pediatric respiratory disease outpatient and emergency visits a central hospital in Minhang District of Shanghai between 2017 and 2019, along with concurrent meteorological data were collected. A distributed lag non-linear models (DLNM) was constructed to explore the specific relationship between pediatric respiratory disease consultations and various environmental factors and to quantify the cumulative lag effects of environmental factors on respiratory disease consultations. Results: Among the environmental factors, temperature, fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), nitrogen dioxide (NO 2), and sulfur dioxide (SO 2) were associated with pediatric respiratory disease visits. After adjusting for temperature, PM 2.5 and PM 10 concentrations did not show significant immediate or lag effects. The relative risk (RR) of pediatric respiratory disease visits increased with rising NO 2 concentrations. When NO 2 concentration ≥55 μg/m 3, significant immediate and lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.05, 1.13, 1.17, and 1.21( P <0.05). The RR values showed an inverted “U” shaped relationship with SO 2 concentrations. When SO 2 concentration ≥5 μg/m 3, significant lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.03 , 1.03, and 1.04 ( P <0.05). Conclusion High concentrations of NO 2 and SO 2 increase the risk of pediatric respiratory disease visits, with observable lag effects.

Objective To evaluate the efficacy and safety of robot-assisted laparoscopic pyeloplasty(RALP)in the treatment of obstructive hydronephrosis at ureteropelvic junction in infants≤6 months old.Methods Clinical data of 44 infants with ureteropelvic junction obstruction(UPJO)and hydronephrosis treated by RALP from January 2021 to December 2023 were analyzed retrospectively.The average age was(72.3±49.7)d(range,5 d-6 months old),and the average weight was(5.7±1.6)kg(range,2.9-8.5 kg).Preoperative ultrasonography showed that the anteroposterior diameter was(30.2±9.5)mm and the thinnest part of the renal parenchyma was(2.6±1.2)mm.By using the da Vinci Xi robotic operating system,the narrow segment of the ureteropelvic junction was fully exposed,the renal pelvis and ureter were trimmed with scissors,and the ureter was anastomosed with 6-0 single strands.Results All the 44 operations were completed successfully without conversion to traditional laparoscopic or open surgery.No intraoperative complications occurred.The operation time was 105-245 min(mean,179.8 min),and the intraoperative blood loss was 2-10 ml(mean,4.9 ml).Re-examinations of ultrasonography at 6 months after removal of double J tube showed that the anteroposterior diameter was(10.5±6.3)mm,which was significantly decreased than that before operation(paired t test,t=19.985,P=0.000),and the thinnest part of the renal parenchyma was(6.8±1.7)mm,which was significantly increased than that before operation(paired t test,t=18.420,P=0.000).The patients were followed up for 6-12 months after removal of double J tube.There were no complications such as anastomotic stricture,urine leakage,or recurrence of obstruction.Conclusion RALP is safe and effective in the treatment of UPJO and hydronephrosis in infants younger than 6 months old.

Objective:To analyze the association between physical activity levels and all-cause mortality risk in patients with diabetic kidney disease (DKD) and to investigate the mediating effect of inflammation.Methods:Based on National Health and Nutrition Examination Survey of America data matched with the National Death Index of America, a prospective cohort was formed, including 59 482 participants from six cycles between 2007 and 2018. After applying inclusion and exclusion criteria, 2 214 DKD patients were selected for the study. Cox proportional hazard regression models were used to analyze the impact of physical activity levels on all-cause mortality risk. The mediating effect of inflammatory markers in the association between physical activity and all-cause mortality risk was explored.Results:There were statistically significant differences in survival curves among different physical activity level groups ( P<0.001). As physical activity levels increased, the risk of mortality decreased. Patients in the high physical activity group had a lower mortality risk compared to those in the inactive group ( HR=0.64, 95% CI: 0.53-0.78), with a statistically significant difference ( P<0.001). Patients with higher physical activity levels had lower levels of inflammation (white blood cell, neutrophil, and C-reactive protein) ( P<0.001). White blood cell, neutrophil, C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), and the systemic inflammation index (SII) were independent risk factors for mortality in DKD patients ( HR>1.00), with higher risk effects observed for the combined indicator lgNLR ( HR=2.06, 95% CI: 1.76-2.41) and lgSII ( HR=1.44, 95% CI: 1.26-1.64). Mediation analysis showed that physical activity had an indirect effect on all-cause mortality risk through neutrophil, with an effect size of -0.033 (95% CI: -0.052 - -0.002), which was statistically significant ( P<0.05), with a mediation effect proportion of 9.75%. Conclusion:Physical activity is a protective factor against all-cause mortality risk in DKD patients, partly through reducing neutrophil levels.

Objective:To evaluate the clinical significance of morular metaplasia (MM) in fertility-preserving treatment for young patients with endometrial hyperplasia and grade 1 endometrial endometrioid carcinoma.Methods:Clinical data was retrospectively collected from patients diagnosed with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma under 40 years old who underwent progestin-based fertility-sparing treatmentat in Tianjin Medical University General Hospital between January 2018 and November 2022.Patients were divided into the MM group (37 cases) and the non-MM group (63 cases) based on pathological findings. Clinical characteristics, hysteroscopic features, treatment efficacy and fertility outcomes were compared between the two groups. The MM group was further stratified into three subgroups based on the timing of MM occurrence:(1) MM-Bef group ( n=10): MM was present in the initial endometrial curettage or hysteroscopic biopsy pathology before fertility-sparing treatment and disappeared after treatment; (2) MM-Sus group ( n=14): MM persisted consistently before and after therapy;(3) MM-Aft group ( n=13): MM was absent before therapy but appeared after treatment. The risk factors which had impact on the treatment outcomes of the patients were analyzed using univariate and multivariate Cox regression analysis. Results:The rate of polycystic ovary syndrome were higher in the MM group than the non-MM group [51% (19/37) vs 27% (17/63), P=0.014]. The complete response (CR) rate was significantly lower in the MM group than in the non-MM group [73% (27/37) vs 95% (60/63), P=0.006], and the median time to CR was significantly longer in the MM group (6.0 vs 5.0 months, P=0.005).Multivariate analysis identified that MM-Sus ( HR=0.355, 95% CI:0.174-0.723; P=0.004) and MM-Aft ( HR=0.314, 95% CI:0.145-0.681; P=0.003) were independent risk factors for delayed CR in fertility-sparing treatment. The patients in the MM group and non-MM group underwent hysteroscopic biopsy for 76 and 131 times. "Gravel-like change" was a more frequent hysteroscopic manifestation in the MM group than that in the non-MM group [18% (14/76) vs 2% (2/131), P<0.001]. Conclusions:Patients in the MM group have poorer treatment outcomes than patients in the non-MM group. MM-Sus and MM-Aft are risk factors for fertility-preserving treatment in young patients with endometrial hyperplasia or grade 1 endometrial endometrioid carcinoma. "Gravel-like change" is the characteristic hysteroscopic manifestations of MM.