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 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.

【Objective】 To explore the therapeutic effect of autologous platelet-rich plasma (PRP) in the treatment of patellofemoral osteoarthritis (PFOA) based on the Magnetic Resonance Observation of Cartilage Repair Tissue 2.0 (MOCART 2.0) knee score system. 【Methods】 A total of 22 patients (28 knees) with PFOA treated by intraarticular PRP injection in our hospital from January 2020 to December 2023 were enrolled in the study. The nuclear magnetic resonance(NMR) images before and after treatment were compared using the MOCART 2.0 knee score system. Visual Analog Scales (VAS) score and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score before and after treatment were evaluated and compared, and adverse reactions were observed during the treatment. 【Results】 The MOCART 2.0 knee score showed no difference before and after treatment (53.4±12.2 vs 49.9±2.1)(P>0.05). In the subgroup analysis, the "signal intensity of the repair tissue" score and the "subchondral changes" score were better than those before treatment as(5.5±1.5)vs(4.6±1.5)and(15.9±4.3)vs(13.2±6.4)(P<0.05). There were no significant changes in indicators as " degree of cartilage filling" , " integration with adjacent cartilage edges" , " repair of tissue surface structure" , " repair of tissue structure" and " bone changes" (P>0.05).The VAS score and WOMAC score gradually decreased at 1 month, 3 months and 6 months after treatment and were better than before treatment (P<0.05). Incidence of adverse reactions was 4% (4/112). 【Conclusion】 Intraarticular PRP injection is an effective and safe option for treatment of PFOA, and can improve the cartilage signal intensity and alleviating subchondral bone edema.

【Objective】 To explore the model of treatment of refractory wounds by apheresis platelet-rich plasma (PRP), and evaluate its efficacy and safety. 【Methods】 PRP treatment was carried out for 34 patients with refractory wounds who were hospitalized in our hospital from June 2020 to December 2023. The patient′s autologous PRP was collected by the blood composition separator. PRP point-like injection and/or direct application along the edge of the wound, or platelet gel (PG) to cover the wound and fill the sinus were used to treat different types of wounds. The frequency of treatment was once to twice a week, with each course of treatment consisting of 4 to 5 sessions. The efficacy was observed and recorded, and the safety was evaluated. 【Results】 Before PRP collection, the basal platelet, white blood cell and red blood cell counts were (321.85±114.64) ×10⁹/L, (9.52±3.21) ×10⁹/L and (4.34±0.62) ×10¹²/L, respectively. The counts of platelets, white blood cells and red blood cells in PRP products were (1 438.53±376.89)×10⁹/L, (1.38±1.03)×10⁹/L and (0.03±0.01)×10¹²/L, respectively. The platelet concentration of PRP products increased by 4.47 times on average, and the sampled bacterial culture was negative. Out of 34 patients treated with PRP, 33 showed improvement in symptoms, while 1 did not respond well due to long-term bedridden and poor compliance. Four patients had mild adverse reactions during PRP collection or treatment, but all were able to complete PRP collection or treatment after standardized treatment. 【Conclusion】 Apheresis PRP products have the advantages of stable quality, safety, reliability and traceability, and can effectively promote the healing of a variety of refractory wounds. Its treatment process is safe and effective, and is worthy of popularization and application.

Objective:To observe the therapeutic efficacy and prognosis of daratumumab combined with chemotherapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) followed by daratumumab and lenalidomide maintenance treatment for primary plasma cell leukemia (PCL).Methods:The clinical data of a patient with primary PCL admitted to the First People's Hospital of Yunnan Province in January 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:The patient was diagnosed with primary PCL and treated with daratumumab combined with BD (bortezomib + dexamethasone) for 1 course and BCDD (bortezomib + cyclophosphamide + liposomaldoxorubicin + dexamethasone) for two courses. The patient was treated with daratumumab combined with allo-HSCT after complete remission. The donor cells were successfully implanted and the chimerism rate of donor cells was 94.36% without acute graft-versus-host disease reaction. And then the patient received intermittent maintenance therapy of daratumumab combined with low dose lenalidomide after transplantation, and the current remission period after transplantation reached 4 months.Conclusions:Daratumumab combined with chemotherapy bridging to allo-HSCT followed by daratumumab and lenalidomide may improve the prognosis of primary PCL and prolong survival time.

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.

Objective:To explore the features and clinical significance of gene mutations in patients with myelodysplastic syndromes with ring sideroblasts (MDS-RS) .Methods:A total of 255 newly diagnosed primary MDS-RS patients were retrospectively reviewed from our center from January2001 to June 2019. SF3B1 gene mutations were detected by Sanger sequencing in 129 patients, and next generation sequencing (NGS) was performed in the other 126 patients using a set of selected 112-genes.Results:A total of 193 (75.7%) patients presented with SF3B1 mutation, predominantly mutant at amino acid position 700 (K700E) ( n=147, 76.2%) . Non-SF3B1 gene mutations were TET2 (16.7%) , ASXL1 (14.3%) , U2AF1 (11.1%) , TP53 (7.9%) , SETBP1 (6.3%) , and RUNX1 (6.3%) . RS 5%-<15% patients had a higher SETBP1 mutation frequency than RS≥15% patients (21.4% vs 4.5%, P=0.044) . Mutation frequencies of other genes were similar in both groups (all P>0.05) . SF3B1 variant allele frequencies (VAF) had positive correlation with marrow RS percentage but without statistical significance in RS 5%-<15% group ( P=0.078, r=0.486) . SF3B1 mutant patients presented with higher marrow RS percentage compared with wild-type patients[40.0% (15.0%-80.0%) vs 25.5% (15.0%-82.0%) , P<0.001], and SF3B1 VAF positively correlated with RS percentage ( P=0.009, rs=0.261) in RS≥15% group. Age, ANC, PLT, mean RBC corpuscular volume, RS percentage, IPSS-R cytogenetics, and IPSS-R risk score were significantly different between patients with SF3B1 mutations and wild-type SF3B1 (all P<0.05) . Multivariable survival analyses adjusted by age and IPSS-R cytogenetics revealed that SF3B1 mutation was an independent favorable prognostic factor ( HR=0.265, 95% CI 0.077-0.917, P=0.036) , and TP53 mutation was an adverse variable independent of SF3B1 mutation ( HR=6.272, 95% CI 1.725-22.809, P=0.005) . According to the mutant status of SF3B1 and TP53, MDS-RS patients were categorized into 4 groups, namely, with SF3B1 and TP53 mutation, with wild-type SF3B1 and TP53, with wild-type SF3B1 but TP53 mutation, and with SF3B1 mutation but wild-type TP53. There was a significant difference for OS among these 4 groups ( P<0.001) . The former 3 groups showed no significant difference in OS in multiple comparisons. However, the SF3B1 mutation but wild-type TP53 group had a better OS than wild-type SF3B1 but TP53 mutation group and wild-type SF3B1 and TP53 group, whereas a similar OS compared with SF3B1 and TP53 mutation group. Conclusion:SF3B1 mutations were prevalent in MDS-RS patients with the most common mutation at amino acid position 700 (K700E) . SF3B1 mutation was an independent favorable prognostic variable, whereas TP53 mutation was an independent adverse variable. SF3B1 mutation could coordinate with TP53 mutation for more sophisticated prognosis stratification in MDS-RS patients.

Objective:To investigate the pathological characteristics of megakaryocytes in myeloproliferative neoplasms(MPN)and their correlations with driver gene mutations.Methods:Trephine specimens administered for 160 patients with MPN from February 2012 to October 2017 were reevaluated according to the World Health Organization(WHO)’s(2016)diagnostic criteria.Results:This cohort of patients included 72(45.0%)men, with the median age of 59(range, 13-87)years, comprising 39 with polycythemia vera(PV), 33 with essential thrombocythemia(ET), 37 with prefibrotic/early-primary myelofibrosis(pre-PMF), 37 with overt PMF, 1 with post-ET MF, 2 with post-PV MF, and 11 with MPN-unclassifiable(MPN-U)after the re-diagnosis. With PV, ET, pre-PMF, and overt PMF changes, proportions of dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes gradually increased, whereas erythropoiesis gradually decreased. Proportions of reticulin, collagen, and osteosclerosis grades of ≥1 also increased. Dense clusters, hypolobulated nuclei, and naked nuclei of megakaryocytes were negatively correlated with erythropoiesis and positively correlated with granulopoiesis and fibrosis. In patients with pre- and overt PMF, dense clusters and naked nuclei of megakaryocytes were positively correlated with fibrosis. Patients with JAK2V617F MPN had significantly increased erythropoiesis( P=0.022). Patients with CALR-mutated MPN were characterized by increased loose and dense clusters; paratrabecular distribution and naked nuclei of megakaryocytes( P=0.055, P=0.002, P=0.018, P=0.008); and increased reticulin, collagen, and osteosclerosis( P=0.003, P<0.001, P=0.001). In patients with pre- and overt PMF, patients with JAK2V617F had increased cellularity( P=0.037). CALR-mutated patients had increased dense clusters and giant sizes of megakaryocytes, collagen, and osteosclerosis( P=0.055, P=0.059, P=0.011, P=0.046). Conclusion:Megakaryocytes showed abnormal MPN morphology and distribution, which were related to fibrosis. CALR mutation was probably associated with abnormal morphology and distribution of megakaryocytes and fibrosis.

Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10⁹/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10⁹/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10⁹/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10⁹/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ²=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.