BACKGROUND:It has been proved clinically that adhesion of fibrous scar with the dura mater or nerve root after lumbar operation is an important factor for postoperative symptoms,such as postoperative pain and numbness. OBJECTIVE:To verify the inhibitory effect of autologous ligamentum flavum on the formation of epidural fibrous scar after lumbar surgery and explore the possible molecular biological mechanism. METHODS:Forty-eight Japanese white rabbits(6-8 months old)were randomly divided into three groups:a ligamentum flavum preservation group,a ligamentum flavum non-preservation group,and an autologous fat reposition group.A lumbar laminectomy model was established in all the three groups of rabbits,and rabbit epidural tissues were collected at 3 and 6 weeks after modeling.Hematoxylin-eosin staining was used to observe histological changes and the number and density of fibroblasts,VG staining was used to observe the percentage of collagen fiber area,and immunohistochemistry was used to observe the expression of transforming growth factor β1 and Smad3 proteins. RESULTS AND CONCLUSION:Hematoxylin-eosin staining results revealed that fibroblasts in the ligamentum flavum preservation group were few and loosely arranged,while the cells in the ligamentum flavum non-preservation and autologous fat reposition groups were more numerous and closely arranged.The number density of fibroblasts in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P＜0.05);however,there was no significant difference between the latter two groups.VG staining results showed that the collagen fibers in the ligamentum flavum preservation group were sparse and distributed unevenly,while a lot of red collagen fibers were gathered in the ligamentum flavum non-preservation and autologous fat reposition groups.The area percentage of collagen fibers in the ligamentum flavum preservation group was lower than that in the ligamentum flavum non-preservation and autologous fat reposition groups at 3 and 6 weeks after surgery(P＜0.05),but there was no significant difference between the latter two groups.The results of immunohistochemistry showed that the degree of positive staining of retained histone the ligamentum flavum preservation group was significantly lower than that of the other two groups.The absorbance value of transforming growth factor β1 and Smad3 in the ligamentum flavum preservation group was significantly lower than that in the other two groups at 3 and 6 weeks after surgery(P＜0.05),but there was no significant difference between the latter two groups.To conclude,there are different degrees of epidural fibrous scar formation after lumbar surgery.If the ligamentum flavum is preserved,it can help to reduce the number of epidural fibroblasts as well as the formation of collagen fibers,thus reducing the adhesion of the fibrous scar tissue to the dural sac and nerve root.The mechanism is not only a purely mechanical blockade,but also to reduce the formation of epidural fibrous scar by interfering with the transforming growth factor β1/Smad3 signaling pathway.

This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.
Humans ; Ossification, Heterotopic/genetics*

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective:To investigate the clinical efficacy and safety of the triplet regimen of flumatinib, venetoclax (VEN) and azacitidine (AZA) for Philadelphia chromosome-positive (Ph +) mixed-phenotype acute leukemia (MPAL). Methods:The clinical data of 2 Ph + MPAL patients treated with triplet regimen of flumatinib, VEN and AZA who were admitted to the Institute of Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College in February and March 2023 were retrospectively analyzed, and the relevant literature was reviewed. Results:Patient 1 was a 56-year-old female, and patient 2 was a 59-year-old male. Both patients were diagnosed with Ph + B cell/myeloid (B/My) MPAL. After the first course of induction chemotherapy with the triplet regimen, patient 1 achieved hematological complete remission (HCR), complete cytogenetic remission (CCyR) and major molecular response (MMR), and patient 2 achieved HCR and CCyR. During the entire treatment process, the adverse reactions of two patients were mainly fever and ≥ grade 3 hematological adverse reactions, which were relieved after the use of antibiotics and intermittent infusion of blood products. When the patient achieved HCR and received consolidation treatment with the same regimen, the adverse reactions were mild. Conclusions:The triplet regimen of flumatinib, VEN and AZA is safe and effective for the treatment of Ph + MPAL, and is a new induction therapy option for such patients.

Objective To construct a model that can predict the risk of diagnosing ABO-blood group sys-tem hemolytic disease of the newborn(ABO-HDN)and to verify its effectiveness.Methods A total of 446 children with neonatal hyperbilirubinemia who met the inclusion criteria and were first diagnosed in this hos-pital from January 2022 to March 2023 were selected as the modeling group,and were divided into the develo-ping group(200 cases)and the non-developing group(246 cases)according to whether ABO-HDN was diag-nosed.Totally 17 potential influencing factors were included for univariate analysis and multi-factor analysis,and independent risk factors were included in R software to establish a Nomogram model to predict the risk of ABO-HDN.Another 105 cases of neonatal hyperbilirubinemia in the hospital from April to September 2023 were selected as the verification group.Results In the modeling group,Logistic regression analysis showed that maternal pregnancy number,prenatal serum titer,hemoglobin level,white blood cell count,creatine ki-nase level and neonatal Apgar 1 min score were all independent risk factors for ABO-HDN(P＜0.05).Multi-variate Logistic regression analysis showed that the area under receiver operating characteristic(ROC)curve of the modeling group was 0.819(95％CI:0.779-0.859),sensitivity was 0.655,specificity was 0.878.In the verification group,the area under ROC curve was 0.867(95％CI:0.800-0.933),the sensitivity was 0.803,and the specificity was 0.773.Conclusion The established predictive model scoring system can effec-tively predict the risk of ABO-HDN.

Objective:To evaluate the effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall.Methods:A retrospective study was conducted to analyze the data from the 83 patients with fracture of acetabular posterior wall who had been consecutively treated by open reduction and internal fixation at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2017 to December 2020. The patients were divided into 2 groups based on involvement of posterior wall impaction. In the impaction group of 33 cases, there were 26 males and 7 females with an age of (47.4±11.6) years; in the non-impaction group of 50 cases, there were 43 males and 7 females with an age of (41.3±12.0) years. The quality of postoperative fracture reduction, the function of the affected hip at the last follow-up, and the complication rate during follow-up were compared between the 2 groups. Multifactorial binary logistic regression and age subgroups were used to analyze the effects of posterior wall impaction on functional outcomes.Results:The age, rate of associated injuries in other body parts, and rate of posterior wall comminution in the impaction group were significantly higher than those in the non-impaction group ( P<0.05), but there was no statistically significant difference in other general data of patients between the 2 groups ( P>0.05). All patients were followed up for (44.5±13.3) months after surgery. The rate of anatomical reduction in the non-impaction group (96.0%, 48/50) was significantly higher than that in the impaction group (57.6%, 19/33) ( P<0.05), and the good and excellent rate by the modified Merle d'Aubigné & Postel scale at the last follow-up in the non-impaction group (84.0%, 42/50) was significantly higher than that in the impaction group (51.5%, 17/33) ( P<0.05). There was no significant difference in the incidence of complications between the 2 groups ( P>0.05). After adjusting for age and gender, the difference in hip function was still significantly different between the 2 groups ( OR=0.23, 95% CI: 0.06 to 0.79, P=0.020). The effect of posterior wall impaction on functional outcomes was statistically significant in patients aged ≥50 years ( P=0.008), whereas the difference was not statistically significant in patients aged <50 years ( P=0.194). Conclusions:Compared with non-impaction ones, acetabular fractures of posterior wall impaction tend to lead to poorer quality of reduction, which in turn affects the postoperative recovery of hip joint function. The impact of impaction fractures on functional recovery is more significant in patients aged 50 years and above.

Objective:To investigate the feasibility of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester.Methods:A retrospective cohort study was conducted to collect 103 pregnant women who were diagnosed with premature rupture of membranes in the second trimester of pregnancy and insisted on continuing the pregnancy in Shanxi Bethune Hospital from July 2012 to July 2022. According to the degree of vaginal fluid, pregnant women were divided into rupture group (with typical vaginal fluid, 48 cases) and leakage group (without typical vaginal fluid, 55 cases). The rupture latency (the time from rupture of membranes to termination of pregnancy), gestational weeks of termination, indications and methods of termination of pregnancy, maternal infection related indicators and perinatal outcomes were compared between the two groups. Univariate regression model was used to analyze the correlation between different degrees of vaginal fluid in pregnant women with premature rupture of membranes and maternal and neonatal outcomes.Results:(1) Obstetric indicators: there was no significant difference in the gestational age of rupture of membranes between the two groups ( P>0.05). However, the proportion of rupture latency >28 days in the leakage group was significantly higher than that in the rupture group [42% (23/55) vs 13% (6/48); χ2=33.673, P<0.001], and the incidence of pregnancy termination ≥28 weeks was significantly higher [47% (26/55) vs 19% (9/48); χ2=9.295, P=0.002]. (2) Indications and methods of termination: the incidence of progressive reduction of amniotic fluid as the indication for termination in the leakage group was significantly lower than that in the rupture group [22% (12/55) vs 42% (20/48); χ2=4.715, P=0.030], and the incidence of full-term termination in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 12% (6/48); χ2=5.008, P=0.025], while there were no significant differences in the indications of termination of pregnancy, including amniotic cavity infection, uterine contraction failure and fetal distress between the two groups (all P>0.05). The incidence of induced labor or spontaneous contraction in the leakage group was significantly lower than that in the rupture group [53% (29/55) vs 81% (39/48); χ2=9.295, P=0.002], while the cesarean section rate and vaginal delivery rate were similar between the two groups (both P>0.05). (3) Infection related indicators: the incidence of amniotic cavity infection in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 13% (6/48); χ2=4.003, P=0.045]. However, there were no significant differences in the elevation of inflammatory indicators, the positive rate of cervical secretion bacterial culture and the incidence of tissue chorioamnionitis between the two groups (all P>0.05). (4) Perinatal outcomes: the live birth rate in the leakage group was significantly higher than that in the rupture group [51% (28/55) vs 27% (13/48); χ2=5.119, P=0.024]. The proportion of live births with 1-minute Apgar score >7 in the leakage group was significantly higher than that in the rupture group [38% (21/55) vs 17% (8/48); χ2=4.850, P=0.028]. However, there were no significant differences in the birth weight of live births and the incidence of neonatal complications between the two groups (all P>0.05). (5) Univariate regression analysis showed that compared with the rupture group, the leakage group had a higher risk of pregnancy termination at ≥28 gestational weeks ( RR=2.521, 95% CI: 1.314-4.838; P=0.002), amniotic infection ( RR=2.473, 95% CI: 1.061-5.764; P=0.025), perinatal survival ( RR=1.880, 95% CI: 1.104-3.199; P=0.014). Conclusion:Compared with pregnant women with typical vaginal fluid in the second trimester of premature rupture of membranes, expectant treatment for pregnant women with atypical vaginal fluid is more feasible, which could effectively prolong the gestational weeks and improve the perinatal live birth rate.

Preimplantation genetic testing is an important part in assisted reproductive technology,which can block the intergenerational inheritance of a single gene or chromosomal diseases.Preimplantation genetic testing for polygenic disease risk(PGT-P)is one of the latest developments in the field.With the development of artificial intelligence and genetic detection technology,PGT-P can be used to analyze genetic material,calculate polygenic risk scores and convert these into incidence probability.Embryos with relatively low incidence probability can be screened for transfer,in order to reduce the possibility that the offspring suffers from the disease in the future.This has significant clinical and social significance.At present,PGT-P has been applied clinically and made phased progress at home and abroad.But as a developing technology,PGT-P still has some technical limitations as unstable results,environmental influences and racial differences cannot be ruled out.From the ethical perspective,if the screening indications are not strictly regulated,it is likely to cause new social problems.In this paper,we review the technical details and recent progress in PGT-P,and discuss the prospects of its future development,especially how to establish a complete and suitable screening model for Chinese population.