ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine （Opn4-DA） axis in myopic mice to inhibit endoplasmic reticulum （ER） stress in the retina and sclera， thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group， a form-deprived myopia group （FDM group）， an intrinsically photosensitive retinal ganglion cells ablation group （ipRGCs group）， a Mingshi Prescription group （MSF group， 5.2 g·kg^-1）， and an ipRGCs + MSF group （5.2 g·kg^-1）. Except for the normal group， all other groups underwent FDM modeling. Additionally， the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling， the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice， eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina， choroid， and sclera were observed using periodic acid-Schiff （PAS） staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor （DRD1）， C/EBP homologous protein （CHOP）， and glucose-regulated protein 78 （GRP78） in the retina， and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4， CHOP， and GRP78 in the retina， and CHOP and GRP78 in the sclera. Immunofluorescence staining （IF） was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group， the FDM group showed a significant myopic shift in refraction （P<0.05） and a significant increase in axial length （P<0.05）. The retinal layers were thinner， the number of ganglion cells was reduced， and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased （P<0.05）， while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased （P<0.05）. Compared with the FDM group， the ipRGCs group exhibited further increases in myopic refraction and axial length （P<0.05）， more pronounced thinning and looseness in the retinal， choroidal， and scleral layers， lower expression of Opn4 and DRD1 protein and mRNA in the retina （P<0.05）， and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera （P<0.05）. Compared with the FDM group， the MSF group showed significantly reduced refractive error and axial length （P<0.05）， with improved cellular number， arrangement， and thickness in ocular tissues， increased Opn4 and DRD1 protein and mRNA expression in the retina （P<0.05）， and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera （P<0.05）. Similarly， the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group （P<0.05）. ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice， thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes， softens the fascia， and restores ocular rhythm.

SARS-CoV-2 and its emerging variants continue to pose a significant global public health threat. The SARS-CoV-2 main protease (M^pro) is a critical target for the development of antiviral agents that can inhibit viral replication and transcription. In this study, we identified chebulagic acid (CHLA), isolated from Terminalia chebula Retz., as a potent non-peptidomimetic and non-covalent M^pro inhibitor. CHLA exhibited intermolecular interactions and provided significant protection to Vero E6 cells against a range of SARS-CoV-2 variants, including the wild-type, Delta, Omicron BA.1.1, BA.2.3, BA.4, and BA.5, with EC₅₀ values below 2 μmol/L. Moreover, in vivo studies confirmed the antiviral efficacy of CHLA in K18-hACE2 mice. Notably, CHLA bound to a unique groove at the interface between M^pro domains I and II, which was revealed by the high-resolution crystal structure (1.4 Å) of the M^pro-CHLA complex, shrinking the substrate binding pocket of M^pro and inducing M^pro aggregation. CHLA was proposed to act as an allosteric inhibitor. Pharmacokinetic profiling and safety assessments underscore CHLA's potential as a promising broad-spectrum antiviral candidate. These findings report a novel binding site on M^pro and identify antiviral activity of CHLA, providing a robust framework for lead compounds discovery and elucidating the underlying molecular mechanisms of inhibition.

Objective:To investigate the clinicopathological characteristics and prognosis of non-specific invasive breast cancer (BIC-NST) patients with and without ductal carcinoma in situ (DCIS).Methods:A retrospective cohort study was conducted. A total of 9 490 female BIC-NST patients who underwent surgery in the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College and the Yuncheng Central Hospital in Shanxi Province from January 2009 to December 2017 were collected. Among them, 4 248 cases (44.8%) had DCIS and 5 242 cases (55.2%) did not have DCIS. The clinicopathological characteristics and prognosis of BIC-NST patients with and without DCIS were compared. Cox proportional hazards model was used to make univariate and multivariate analysis on the influencing factors of overall survival (OS) and disease-free survival (DFS) in BIC-NST patients.Results:Compared with patients without DCIS, patients with DCIS were younger [(51±11) years vs. (53±11) years, t = -8.75, P < 0.001], had a lower proportion of breast conserving surgery [19.2% (815/4 248) vs. 21.2% (1 113/5 242), χ2 = 6.07, P = 0.010], a higher proportion of pathological T 1 stage [60.2% (2 558/4 248) vs. 57.5% (3 016/5 242), χ2 = 6.96, P = 0.008], a lower histological grade, a lower Ki-67 positivity index [(28±19)% vs. (31±22)%, χ2 = -5.84, P < 0.001], a higher proportion of lymphatic vessel invasion [18.3% (777/4 248) vs. 15.9% (831/ 5 242), χ2 = 9.91, P = 0.002], higher positivity rates of hormone receptor (HR) [78.9% (3 278/4 248) vs. 76.2% (3 907/5 242), χ2 = 9.02, P = 0.003] and human epidermal growth factor receptor 2 (HER2) [31.3% (1 236/4 248) vs. 21.2% (1 029/5 242), χ2 = 117.64, P < 0.001], a lower proportion of patients with HR - HER2 - [9.0% (353/ 4 248) vs. 16.5% (800/5 242), χ2 = 138.68, P < 0.001] and HR + HER2 - [59.8% (2 354/4 248) vs. 62.4% (3 026/5 242), χ2 = 8.50, P = 0.004]. Survival analysis showed that there were no statistically significant differences in OS and DFS between patients with and without DCIS ( χ2 = 1.05, P = 0.310; χ2 = 0.42, P = 0.520). Univariate analysis showed that DCIS had no effect on the OS ( HR = 0.926, 95% CI: 0.799-1.073, P = 0.306) and DFS ( HR = 1.040, 95% CI: 0.924-1.170, P = 0.518) of BIC-NST patients. Conclusions:The clinicopathological characteristics of BIC-NST patients with and without DCIS are different, while the presence of DCIS does not affect the prognosis of BIC-NST patients.

BACKGROUND:Facet joint osteoarthritis is acknowledged as a significant contributor to lower back pain in the geriatric population.The advent of an innovative spinal facet joint fusion device presents a therapeutic option for intervening during the initial stages of facet joint osteoarthritis,and significantly reduces the incidence of a series of complications caused by poor early conservative treatment and late surgical treatment.However,its effect on the biomechanics of the lumbar spine is unknown.OBJECTIVE:To investigate the biomechanical disparities between the novel lumbar zygapophyseal joint fusion device and traditional fusion devices.METHODS:A comprehensive three-dimensional finite element model of the L3-S1 lumbar spine was established and validated.Based on this intact model,three groups of surgical models were constructed:a bilateral pedicle screw fixation model,a bilateral novel facet joint fusion fixation model,and a bilateral facet screw fixation model,with the surgical segment designated as L4-5.Under a load of 500 N,a torque of 7.5 Nm was applied to all lumbar models to calculate the range of motion,displacement values,and intervertebral disc stress values at the L4-5 segment;stress values at the L3-4 and L5-S1 segments were also measured.RESULTS AND CONCLUSION:(1)Compared with the intact model,the range of motion at the L4-5 segment was reduced in all surgical models.(2)The novel device exhibited the smallest range of motion at the L4-5 segment under left and right rotational conditions;the greatest range of motion at the L4-5 segment under extension conditions;and a greater range of motion under other conditions than the bilateral pedicle screw fixation model.(3)The novel device demonstrated the smallest displacement values at the L4-5 segment under left and right rotational conditions;under other conditions,the displacement values at the L4-5 segment were greater than those in the bilateral pedicle screw fixation model.(4)In terms of stress distribution at the L4-5 segment,the novel device consistently exhibited the smallest values across all conditions.(5)For the L3-4 segment,the novel device showed the greatest stress values under extension and left and right rotational conditions,while under other conditions,the values were lower than those in the bilateral pedicle screw fixation model.(6)Compared with pedicle screw fixation,the novel device produced smaller stress values at the L5-S1 segment.(7)This study indicates that,compared with pedicle screw fixation,the novel device impacts the biomechanics of the lumbar spine by fusing the facet joints.It provides stability while preserving the range of motion at the surgical segment and reduces stress on the intervertebral discs of the surgical and adjacent segments,thereby potentially delaying disc degeneration.This suggests that the novel device can achieve biomechanical effects similar to those of pedicle screw fixation in theory.

Objective:To evaluate the clinical value of sacral canal posterior wall reconstruction in the treatment of symptomatic sacral canal cysts.Methods:A retrospective cohort study was conducted.The clinical data of 80 patients with symptomatic sacral cysts who underwent surgical treatment at Beijing Friendship Hospital, Capital Medical University, between June 2018 and September 2024 were collected. There were 19 males and 61 females, with an average age of (49.0±11.3) years (ranged from 23-76 years). The patients were divided into the traditional group ( n=30) and the reconstruction group ( n=50) based on the surgical approach. The traditional group underwent the conventional surgical method without reconstruction of the posterior wall of the sacral canal, while the reconstruction group underwent posterior wall reconstruction of the sacral canal. Postoperative observations included the integrity of the sacral canal posterior wall, wound healing, and symptom improvement in both groups. Measurement data with normal distribution were expressed as mean±standard deviation( ± s). Independent samples t-test was used for comparisons of measurement data between groups. Categorical data were compared using the chi-square test or Fisher′s exact test. Ordinal data were analyzed using the Mann-Whitney U test. Pearson correlation analysis was used to assess the relationship between variables. Results:Among the 80 patients, the sacral bone integrity score in the reconstruction group was (1.42±0.49) scores, compared to (3.00±0.00) scores in the traditional group, the reconstruction group showed significantly better results ( P<0.05). Symptom improvement was also significantly different between the two groups ( P=0.038): in the traditional group, 17 patients experienced complete symptom resolution, 6 partial improvement, 7 no improvement, and 0 worsening; in the reconstruction group, 37 had complete symptom resolution, 11 partial improvement, 2 no improvement, and 0 worsening. The effective improvement rate (complete+ partial improvement) in the reconstruction group was significantly better than that in the traditional group ( P=0.012). In terms of wound healing, 76 cases healed well, 4 had delayed healing, and 0 had infections. In the traditional group, 27 healed well, 3 had delayed healing, 0 infections; in the reconstruction group, 49 healed well, 1 had delayed healing, and 0 infections. There was no significant difference in wound healing rate between the two groups ( P=0.146). A significant positive correlation was found between sacral canal posterior wall integrity and symptom improvement ( r=0.288, P=0.010). Conclusion:Sacral canal posterior wall reconstruction significantly improves postoperative anatomical integrity and clinical outcomes without increasing complications, supporting its adoption as a preferred surgical approach for symptomatic sacral canal cysts.

Objective:To evaluate the factors influencing test failure after resampling in non-invasive prenatal testing (NIPT) and to explore its impact on pregnancy outcomes.Methods:The information of pregnant women who failed to undergo NIPT for the first time and resampled for testing in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to January 2022 were collected and retrospectively analyzed. According to the results of resampled NIPT, the pregnant women were divided into the failure group (170 cases) and the success group(485 cases), and the general clinical data and pregnancy outcomes of the two groups were compared.Results:(1) A total of 88 928 pregnant women underwent NIPT in Beijing Obstetrics and Gynecology Hospital during the study period, of which 1 299 (1.461%, 1 299/88 928) failed in the first NIPT. Among the 1 299 pregnant women who failed in the first NIPT, 720 were resampled for testing. Finally, 655 pregnant women who met the inclusion criteria and had complete clinical information and perinatal outcomes were collected. The success rate of resampling was 74.0% (485/655). Compared with the success group, the pregnant women in the failure group had a later gestational age at resampling, a higher pre-pregnancy body mass index (BMI) and a higher fetal fraction, and the differences were statistically significant (all P<0.001). (2) Among the 485 pregnant women in the success group, 130 cases (26.8%, 130/485) were detected with chromosome aneuploidy. Among the 170 pregnant women in the failure group, 8 cases had abnormal amniocentesis, 2 cases had abnormal maternal serum screening of aneuploidy in the second trimester, 3 cases had abnormal ultrasound anomaly removal, and 157 cases had no abnormality. (3) The incidence of fetal or neonatal malformation in the failure group was significantly higher than that in the success group [11.2% (19/170) vs 5.8% (28/485), P=0.019], but after adjusting for age and pre-pregnancy BMI, fetal or neonatal malformation was not associated with the success of resampling ( RR=0.675, 95% CI: 0.346-1.319; P=0.250). The incidences of gestational diabetes mellitus and hypertensive disorders in pregnancy in the failure group were significantly higher than those in the success group (all P<0.05), but after adjusting for age and pre-pregnancy BMI, only the incidence of gestational diabetes mellitus in the failure group was higher ( RR=0.630, 95% CI: 0.426-0.932; P=0.021). Conclusions:For pregnant women who failed the initial NIPT, the success of the resampling test is associated with pre-pregnancy BMI and the gestational week at the time of resampling. Those who failed the resampling test are more likely to develop gestational diabetes mellitus. When providing genetic counseling for pregnant women who failed the initial NIPT, it is important to consider the successful rate of resampling testing. The risk of chromosomal abnormalities should be comprehensively considered to develop further screening strategies.

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.

Objective:To evaluate the factors influencing test failure after resampling in non-invasive prenatal testing (NIPT) and to explore its impact on pregnancy outcomes.Methods:The information of pregnant women who failed to undergo NIPT for the first time and resampled for testing in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2018 to January 2022 were collected and retrospectively analyzed. According to the results of resampled NIPT, the pregnant women were divided into the failure group (170 cases) and the success group(485 cases), and the general clinical data and pregnancy outcomes of the two groups were compared.Results:(1) A total of 88 928 pregnant women underwent NIPT in Beijing Obstetrics and Gynecology Hospital during the study period, of which 1 299 (1.461%, 1 299/88 928) failed in the first NIPT. Among the 1 299 pregnant women who failed in the first NIPT, 720 were resampled for testing. Finally, 655 pregnant women who met the inclusion criteria and had complete clinical information and perinatal outcomes were collected. The success rate of resampling was 74.0% (485/655). Compared with the success group, the pregnant women in the failure group had a later gestational age at resampling, a higher pre-pregnancy body mass index (BMI) and a higher fetal fraction, and the differences were statistically significant (all P<0.001). (2) Among the 485 pregnant women in the success group, 130 cases (26.8%, 130/485) were detected with chromosome aneuploidy. Among the 170 pregnant women in the failure group, 8 cases had abnormal amniocentesis, 2 cases had abnormal maternal serum screening of aneuploidy in the second trimester, 3 cases had abnormal ultrasound anomaly removal, and 157 cases had no abnormality. (3) The incidence of fetal or neonatal malformation in the failure group was significantly higher than that in the success group [11.2% (19/170) vs 5.8% (28/485), P=0.019], but after adjusting for age and pre-pregnancy BMI, fetal or neonatal malformation was not associated with the success of resampling ( RR=0.675, 95% CI: 0.346-1.319; P=0.250). The incidences of gestational diabetes mellitus and hypertensive disorders in pregnancy in the failure group were significantly higher than those in the success group (all P<0.05), but after adjusting for age and pre-pregnancy BMI, only the incidence of gestational diabetes mellitus in the failure group was higher ( RR=0.630, 95% CI: 0.426-0.932; P=0.021). Conclusions:For pregnant women who failed the initial NIPT, the success of the resampling test is associated with pre-pregnancy BMI and the gestational week at the time of resampling. Those who failed the resampling test are more likely to develop gestational diabetes mellitus. When providing genetic counseling for pregnant women who failed the initial NIPT, it is important to consider the successful rate of resampling testing. The risk of chromosomal abnormalities should be comprehensively considered to develop further screening strategies.

BACKGROUND:Facet joint osteoarthritis is acknowledged as a significant contributor to lower back pain in the geriatric population.The advent of an innovative spinal facet joint fusion device presents a therapeutic option for intervening during the initial stages of facet joint osteoarthritis,and significantly reduces the incidence of a series of complications caused by poor early conservative treatment and late surgical treatment.However,its effect on the biomechanics of the lumbar spine is unknown.OBJECTIVE:To investigate the biomechanical disparities between the novel lumbar zygapophyseal joint fusion device and traditional fusion devices.METHODS:A comprehensive three-dimensional finite element model of the L3-S1 lumbar spine was established and validated.Based on this intact model,three groups of surgical models were constructed:a bilateral pedicle screw fixation model,a bilateral novel facet joint fusion fixation model,and a bilateral facet screw fixation model,with the surgical segment designated as L4-5.Under a load of 500 N,a torque of 7.5 Nm was applied to all lumbar models to calculate the range of motion,displacement values,and intervertebral disc stress values at the L4-5 segment;stress values at the L3-4 and L5-S1 segments were also measured.RESULTS AND CONCLUSION:(1)Compared with the intact model,the range of motion at the L4-5 segment was reduced in all surgical models.(2)The novel device exhibited the smallest range of motion at the L4-5 segment under left and right rotational conditions;the greatest range of motion at the L4-5 segment under extension conditions;and a greater range of motion under other conditions than the bilateral pedicle screw fixation model.(3)The novel device demonstrated the smallest displacement values at the L4-5 segment under left and right rotational conditions;under other conditions,the displacement values at the L4-5 segment were greater than those in the bilateral pedicle screw fixation model.(4)In terms of stress distribution at the L4-5 segment,the novel device consistently exhibited the smallest values across all conditions.(5)For the L3-4 segment,the novel device showed the greatest stress values under extension and left and right rotational conditions,while under other conditions,the values were lower than those in the bilateral pedicle screw fixation model.(6)Compared with pedicle screw fixation,the novel device produced smaller stress values at the L5-S1 segment.(7)This study indicates that,compared with pedicle screw fixation,the novel device impacts the biomechanics of the lumbar spine by fusing the facet joints.It provides stability while preserving the range of motion at the surgical segment and reduces stress on the intervertebral discs of the surgical and adjacent segments,thereby potentially delaying disc degeneration.This suggests that the novel device can achieve biomechanical effects similar to those of pedicle screw fixation in theory.

Objective:To investigate the short-term clinical efficacy of implantation with a 3D-printed microporous titanium prosthesis in the treatment of large segmental infectious tibial defects.Methods:A retrospective analysis was conducted of the electronic medical records of the 47 patients with large segmental tibial defects who had been treated with 3D-printed microporous titanium prostheses at Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force from January 2019 to February 2024. The cohort included 36 males and 11 females, with an age of (46.2±11.8) years and a mean bone defect length of 12.3 (8.0, 16.8) cm. In the 19 patients complicated with soft tissue defects, the area of soft tissue defects ranged from 10.0 cm × 6.0 cm to 33.0 cm × 10.0 cm. For the 28 patients without soft tissue defects at the lower leg, the bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage; for the 19 patients complicated with soft tissue defects, the soft tissue defects at the lower limb were repaired using an anterolateral thigh flap with vascular anastomosis at the same time when bone defects were filled with vancomycin-loaded calcium sulfate bone cement at the first stage. After infection control at 2 to 8 months after surgery, individualized 3D-printed microporous titanium prostheses were implanted at the second stage to reconstruct the bone defects. Postoperative observations included the patients' first standing time, crutch walking time, full weight-bearing time, osseointegration of the tibial fracture and the prosthesis, and complications during follow-up.Results:The follow-up period for the 47 patients was (34.7±14.3) months. The first standing time was (2.2±0.6) months, crutch walking time (3.8±1.1) months, and full weight-bearing time (5.3±1.2) for this cohort. The evaluation by the Paley's bone healing score resulted in 25 excellent cases, 18 good cases, 1 medium case, and 3 poor cases, giving an excellent and good rate of 91.5% (43/47). One year after operation, the X-ray films showed that the tibial fractures and prostheses were well integrated in the 43 patients. Two patients developed recurrent tibial infection which was responded to replacement of the vancomycin-loaded calcium sulfate spacer. The fixation screws for tibial prosthesis were broken in one patient, but no recurrence of infection was observed after revision. The overall incidence of complications was 6.4% (3/47).Conclusion:In the treatment of large segmental infectious tibial defects, by facilitating rapid functional recovery and ensuring a low incidence of complications, implantation with a 3D-printed microporous titanium prosthesis demonstrates fine short-term clinical efficacy.