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.

Objective:To evaluate the efficacy, safety, and prognostic factors of transarterial chemoembolization (TACE) combined with molecular targeted therapy (MTT) and camrelizumab in patients with unresectable recurrent hepatocellular carcinoma (urHCC).Methods:Clinical data of 83 patients with urHCC treated at the First Affiliated Hospital of the University of Science and Technology of China between October 2018 and October 2023 were retrospectively analyzed, including 75 males and 8 females, aged (55.2±10.7) years. Among them, 43 patients received TACE combined with MTT and camrelizumab (observation group), while 40 received TACE combined with MTT alone (control group). Kaplan-Meier curves were plotted to compare overall survival (OS) and progression-free survival (PFS) between the groups. Treatment response was assessed according to the mRECIST criteria, and objective response rate (ORR) and disease control rate (DCR) were compared. Adverse events (AEs) were monitored in both groups.Results:The observation group demonstrated longer median OS (31.8 vs 19.9 months, χ2=11.26, P=0.001) and median PFS (14.5 vs 7.4, months, χ2=4.08, P=0.043) compared to the control group. The ORR and DCR in the observation group were 51.2% (22/43) and 90.1% (39/43), respectively, both higher than those in the control group [25.0% (10/40) and 70.0% (28/40), respectively]. The differences were statistically significant ( χ2=5.99, 5.71; P=0.023, 0.025; respectively). Multivariate Cox analysis showed that different treatment regimens were influencing factors for post-treatment survival in patients with urHCC (control group vs treatment group: HR=2.633, 95% CI: 1.483- 4.677, P<0.001), as well as for PFS (control group vs treatment group: HR=1.781, 95% CI: 1.116-2.842, P=0.015). No treatment-related deaths or unexpected AEs occurred in either group. The most common systemic therapy-related AE was hand-foot syndrome, observed in 15 patients (34.9%, 15/43) in the observation group and 9 (22.5%, 9/40) in the control group ( χ2=1.55, P=0.236). Conclusions:Compared to TACE combined with MTT alone, TACE combined with MTT and camrelizumab demonstrates superior efficacy and acceptable safety in treating unresectable recurrent HCC.

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 efficacy, safety, and prognostic factors of transarterial chemoembolization (TACE) combined with molecular targeted therapy (MTT) and camrelizumab in patients with unresectable recurrent hepatocellular carcinoma (urHCC).Methods:Clinical data of 83 patients with urHCC treated at the First Affiliated Hospital of the University of Science and Technology of China between October 2018 and October 2023 were retrospectively analyzed, including 75 males and 8 females, aged (55.2±10.7) years. Among them, 43 patients received TACE combined with MTT and camrelizumab (observation group), while 40 received TACE combined with MTT alone (control group). Kaplan-Meier curves were plotted to compare overall survival (OS) and progression-free survival (PFS) between the groups. Treatment response was assessed according to the mRECIST criteria, and objective response rate (ORR) and disease control rate (DCR) were compared. Adverse events (AEs) were monitored in both groups.Results:The observation group demonstrated longer median OS (31.8 vs 19.9 months, χ2=11.26, P=0.001) and median PFS (14.5 vs 7.4, months, χ2=4.08, P=0.043) compared to the control group. The ORR and DCR in the observation group were 51.2% (22/43) and 90.1% (39/43), respectively, both higher than those in the control group [25.0% (10/40) and 70.0% (28/40), respectively]. The differences were statistically significant ( χ2=5.99, 5.71; P=0.023, 0.025; respectively). Multivariate Cox analysis showed that different treatment regimens were influencing factors for post-treatment survival in patients with urHCC (control group vs treatment group: HR=2.633, 95% CI: 1.483- 4.677, P<0.001), as well as for PFS (control group vs treatment group: HR=1.781, 95% CI: 1.116-2.842, P=0.015). No treatment-related deaths or unexpected AEs occurred in either group. The most common systemic therapy-related AE was hand-foot syndrome, observed in 15 patients (34.9%, 15/43) in the observation group and 9 (22.5%, 9/40) in the control group ( χ2=1.55, P=0.236). Conclusions:Compared to TACE combined with MTT alone, TACE combined with MTT and camrelizumab demonstrates superior efficacy and acceptable safety in treating unresectable recurrent HCC.

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 analyze the causal relationship between serum sex steroid hormone levels and myopia with the Mendelian randomization(MR)methods.Methods Sex hormone genetic tools classified by sex were publicly availa-ble summarized statistical data from the Genome-wide association study(GWAS)of the UK Biobank Consortium on sex hormone-binding globulin(SHBG),total testosterone(TT),bioavailable testosterone(BT),and estradiol(E2).The GWAS summarized statistical data for myopia were obtained from publicly available data published by the FinnGen Consorti-um R10.All data were downloaded from April 18 to April 31,2024 from the corresponding databases and analyzed.All re-sults from the MR study were mainly analyzed by inverse-variance weighting(IVW)method.Results The study showed that a higher serum SHBG level in European increased the risk of myopia development in women(IVW,OR=1.152,95％CI:1.014-1.308,P=0.029);low serum TT level(IVW,OR=0.821,95％CI:0.697-0.967,P=0.018)and serum BT lev-el(IVW,OR=0.820,95％CI:0.691-0.972,P=0.022)increased the risk of myopia development in women.There was no causal relationship between serum SHBG,TT,and BT levels and myopia in men.There was no causal effect between E2 level and myopia in women and men.The stability of our findings was supported by sensitivity analysis.Conclusion In-creased serum SHBG level and decreased serum TT and BT levels are associated with an increased risk of myopia in women,whereas no such association is found in men.There is no causal relationship between E2 and myopia.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Objective:To analyze and evaluate the oral diseases burden in China from 1990 to 2021,and provide references on oral health policies making and adjustment. Methods:Using the Global Burden of Disease Study 2021 (GBD 2021) results,it described the trend of Disability Adjusted Life Years (DALYs) and DALYs rates from 1990 to 2021,analyzed the population and disease distribution and made an international comparisons. Results:From 1990 to 2021,the DALYs increased from 2.355 million person-years to 4.4001 million person-years,and the DALYs rate increased from 188.20 person-years/105 to 309.27 person-years/105. In terms of population distribution,the DALYs of oral diseases in females (2.3548 million person-years) were higher than that in males (2.0453 million person-years) in 2021,and the burden was clustered in middle-aged and elderly people. In terms of disease composition,the proportion of edentulism was more than 40％. In terms of international comparison,the DALYs accounted for 18.95％ of the world,and ranked first. The DALYs rate is in the middle,far lower than that of developed countries. Conclusion:From 1990 to 2021,the burden of oral diseases was on the rise,which was heavier than that in other countries. Moreover,there were differences between population and diseases. Attention should be paid to preventing and reducing the risk of disease and actively carry out treatment.