Visual supplementation is an effective tool in cataract surgery counselling by eye-care practitioners.

BACKGROUND: Informed consent constitutes an important aspect of eye care. However, patients often experience difficulties understanding and retaining information presented to them during consultations. This study investigates the efficacy of pictorial aids in supplementing preoperative counselling of patients undergoing cataract surgery. METHODS: Patients attending routine pre-cataract surgery counselling were randomized to receive either a standard verbal consultation (control) or a verbal consultation with a digitalized pictorial aid illustrating key surgical steps (intervention). Patients were assessed after the consultation on their knowledge, satisfaction, anxiety and preparedness using an anonymous questionnaire. RESULTS: Seventy-six patients were recruited and randomized into the control and intervention groups. The intervention group attained better Knowledge Scores (control: 5 [2-6] vs. intervention: 6 [6]), and more patients "strongly agreed" that they were more prepared (control: 78.9% vs. intervention: 97.4%, P=0.028). A higher proportion of patients in the control group either "disagreed" or "neither disagree nor agreed (neutral)" that they were less worried (control: 15.8% vs. intervention: 0.0%, Fisher's Exact Test P=0.025). Although the consultation duration was shorter in the intervention group (21±4mins vs. 27±6mins, P<0.001), the use of digital pictorial aids during consultation resulted in more effective counselling with increased patient knowledge, easier decision-making process and reduced patient anxiety. CONCLUSION: Pictorial aids add to the repository of tools available to eye-care practitioners and are low-cost, easy to implement, and can effectively augment existing preoperative counselling processes to ensure accurate and effective preoperative counselling of patients.

[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

Dietary supplementation of proteases on growth performance, nutrient digestibility, blood characteristics and gut microbiota of growing pigs fed sorghum-based diets.

Low-tannin sorghum is an excellent energy source in pig diets. However, sorghum contains several anti-nutritional factors that may have negative effects on nutrient digestibility. The impacts of proteases on growth performance, nutrient digestibility, blood parameters, and gut microbiota of growing pigs fed sorghum-based diets were studied in this study. Ninety-six pigs (20.66 ± 0.65 kg BW) were allocated into three groups (eight pens/group, four pigs/pen): (1) CON (control diet, sorghum-based diet included 66.98% sorghum), (2) PRO1 (CON + 200 mg/kg proteases), (3) PRO2 (CON + 400 mg/kg proteases) for 28 d. No differences were observed in growth performance and apparent total tract digestibility (ATTD) of nutrients between CON and PRO1 groups. Pigs fed PRO2 diet had increased (P < 0.05) BW on d 21 and 28, and increased (P < 0.05) average daily gain during d 14-21 and the overall period compared with pigs fed CON diet. In addition, pigs fed PRO2 diet had improved (P < 0.05) ATTD of gross energy, CP, and DM compared with pigs fed CON and PRO1 diets. Pigs fed PRO2 diet had lower (P < 0.05) plasma globulin (GLB) level and higher (P < 0.05) plasma glucose, albumin (ALB) and immunoglobulin G levels, and ALB/GLB ratio than pigs fed CON and PRO1 diets. Furthermore, pigs fed PRO2 diet had decreased (P < 0.05) the relative abundance of Acidobacteriota at the phylum level and increased (P < 0.05) the relative abundance of Prevotella_9 at the genus level. The linear discriminant analysis effect size analysis also showed that pigs fed PRO2 diet had significantly enriched short-chain fatty acid-producing bacteria, such as Subdoligranulum and Parabacteroides. In conclusion, protease supplementation at 400 mg/kg improved the growth performance of growing pigs fed sorghum-based diets, which may be attributed to the improvement of nutrient digestibility, host metabolism, immune status and associated with the altered gut microbiota profiles.

[Clinical and pathological characteristics and prognosis analysis of gray zone lymphoma].

To explore the clinical and pathological characteristics as well as therapies and prognosis of gray zone lymphoma (GZL). The clinical data of 10 GZL patients admitted to the First Affiliated Hospital of Soochow University from December 2016 to December 2022 were retrospectively collected. The clinical and pathological characteristics, therapies and prognosis were analyzed. The cut-off time for follow-up visits was December 31, 2022, and the median time for follow-up visits [M(Q1, Q3)] was 40.0 (28.3, 59.8) months. Treatment efficacy was divided into complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD).　There were 6 males and 4 females, with a median age [M(Q1, Q3)] of 33.5 (27.3-39.5) years. Among them, 8 patients had mediastinal (thymus) involvement and 7 patients were accompanied with extranodal involvement. According to Ann Arbor staging, 1 case was in the limited stage and 9 cases were in the progressive stage. The immunophenotypes of 4 patients were strong expression of CD20, expression of CD30, and no expression of CD15. The immunophenotypes of 6 patients were unequal expression of CD20 and strong expression of CD30 and CD15. One patient received classical hodgkin lymphoma(cHL)-like immunochemotherapy and only achieved PR, and then received enhanced diffuse large b-cell lymphoma (DLBCL)-like immunochemotherapy to achieve CR. Five patients received enhanced DLBCL-like immunochemotherapy for induction therapy and achieved CR. All 4 patients who did not achieve CR achieved CR after receiving second-line or third-line salvage therapy. All patients were given autologous stem cell transplantation (ASCT) for consolidation therapy. One patient relapsed and died during the follow-up visit in the 33rd month, and the remaining patients currently maintained a state of sustained remission. It is found that GZL mostly occurs in young patients, mediastinal involvement is common, and diagnosis relies on pathological morphology and immunophenotype. GZL may be more sensitive to DLBCL-like intensive immune regimens. Sequential ASCT for consolidation can reduce the risk of relapse.

An analysis of emerging food safety and fraud risks of novel insect proteins within complex supply chains.

Food consumption play a crucial role in human life, yet conventional food production and consumption patterns can be detrimental to the environment. Thus, research and development has been directed towards alternative proteins, with edible insects being promising sources. Edible insects have been recognised for their sustainable benefits providing protein, with less emission of greenhouse gas, land and water usage compared to sources, such as beef, chicken, and dairy products. Among the over 2000 known edible insect species, only four, namely yellow mealworm (Tenebrio molitor), migratory locust/grasshopper (Locusta migratoria), grain mould beetle, also known as lesser mealworm which is a larval form of Alphitobius diaperinus (from the family of Tenebrionidae of darkling beetles) and house cricket (Acheta domesticus), are currently authorised in specific products through specific producers in the EU. The expansion of such foods into Western diets face challenges such as consumer barriers, gaps in microbiological and chemical safety hazard data during production and processing, and the potential for fraudulent supply chain activity. The main aim of this study was to map the supply chain, through interviews with personnel along the supply chain, coupled with searches for relevant publications and governmental documents. Thus, the main potential points of food safety and fraud along the edible insect supply chain were identified. Feed substrate was identified as the main area of concern regarding microbiological and chemical food safety and novel processing techniques were forecast to be of most concern for future fraudulent activity. Despite the on-going authorisation of insect species in many countries there are substantial food safety and authenticity information gaps in this industry that need to be addressed before edible insects can be viewed as a safe and sustainable protein sources by Western consumers.

Single-Cell Transcriptomic Analysis of Dental Pulp and Periodontal Ligament Stem Cells.

The regeneration of periodontal, periapical, and pulpal tissues is a complex process requiring the direct involvement of cells derived from pluripotent stem cells in the periodontal ligament and dental pulp. Dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs) are spatially distinct with the potential to differentiate into similar functional and phenotypic cells. We aimed to identify the cell heterogeneity of DPSCs and PDLSCs and explore the differentiation potentials of their specialized organ-specific functions using single-cell transcriptomic analysis. Our results revealed 7 distinct clusters, with cluster 3 showing the highest potential for differentiation. Clusters 0 to 2 displayed features similar to fibroblasts. The trajectory route of the cell state transition from cluster 3 to clusters 0, 1, and 2 indicated the distinct nature of cell differentiation. PDLSCs had a higher proportion of cells (78.6%) at the G1 phase, while DPSCs had a higher proportion of cells at the S and G2/M phases (36.1%), mirroring the lower cell proliferation capacity of PDLSCs than DPSCs. Our study suggested the heterogeneity of stemness across PDLSCs and DPSCs, the similarities of these 2 stem cell compartments to be potentially integrated for regenerative strategies, and the distinct features between them potentially particularized for organ-specific functions of the dental pulp and periodontal ligament for a targeted regenerative dental tissue repair and other regeneration therapies.

Regional variations in retinopathy of prematurity incidence for preterm infants <32 weeks' gestation in China.

OBJECTIVES: National-level data on the incidence of retinopathy of prematurity (ROP) in different regions of China is insufficient. This study aimed to compare ROP incidences and care practices in different regions of China and their relationship with regional gross domestic product (GDP) per capita. STUDY DESIGN: Retrospective cohort study. METHODS: All infants born at <32 weeks gestational age (GA) and admitted to 70 neonatal intensive care units (NICUs) from January 1, 2019, to December 31, 2020, were enrolled. Hospitals were categorised into three regional groups according to geographical locations and GDP per capita from high to low: Eastern, Central, and Western China. The incidence of death or ROP, and care practices were compared among the groups. RESULTS: A total of 18,579 infants were enrolled. Median GA was 29.9 (interquartile range 28.4-31.0) weeks and birth weight was 1318.1 (317.2) g. The percentage of GA <28 weeks, complete administration of antenatal steroids, and weight gain velocity during NICU stay were highest in Eastern China and lowest in Western China (all P < 0.01). In Eastern, Central, and Western China, the rates of death or any stage of ROP were 33.3%, 38.5%, and 39.2%, respectively (P < 0.01). CONCLUSIONS: There were considerable regional disparities in ROP incidence in preterm infants with GA <32 weeks in China. The incidence of death or ROP ranged from high to low in Western, Central, and Eastern China.

[Humanized anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.

Single-crystal growth, structure and thermal transport properties of the metallic antiferromagnet Zintl-phase ß-EuIn2As2.

Zintl-phase materials have attracted significant research interest owing to the interplay of magnetism and strong spin-orbit coupling, providing a prominent material platform for axion electrodynamics. Here, we report the single-crystal growth, structure, magnetic and electrical/thermal transport properties of the antiferromagnet layer Zintl-phase compound ß-EuIn2As2. Importantly, the new layered structure of ß-EuIn2As2, in rhombohedral (R3̄m) symmetry, contains triangular layers of Eu2+ ions. The in-plane resistivity ρ(H, T) measurements reveal metal behavior with an antiferromagnetic (AFM) transition (TN ∼ 23.5 K), which is consistent with the heat capacity Cp(H, T) and magnetic susceptibility χ(H, T) measurements. Negative MR was observed in the temperature range from 2 K to 20 K with a maximum MR ratio of 0.06. Unique 4f7J = S = 7/2 Eu2+ spins were supposed magnetically order along the c-axis. The Seebeck coefficient shows a maximum thermopower |Smax| of about 40 µV K-1. The kink around 23 K in the Seebeck coefficient originates from the effect of the antiferromagnetic phase on the electron band structure, while the pronounced thermal conductivity peak at around 10 K is attributed to the phonon-phonon Umklapp scattering. The results suggest that the Eu2+ spin arrangement plays an important role in the magnetic, electrical, and thermal transport properties in ß-EuIn2As2, which might be helpful for future potential technical applications.

[Analysis of etiology and complications in children with stage 5 chronic kidney disease].

Objective: To investigate the etiology, complications, and prognostic factors of stage 5 chronic kidney disease (CKD5) in children. Methods: A case series study was conducted to retrospectively analyze the general situation, clinical manifestations, laboratory tests, genetic testing, and follow-up data (until October 2022) of 174 children with CKD5 who were diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from April 2012 to April 2021. The characteristics of complications in the children were compared based on age, gender, and etiology. Based on the presence or absence of left ventricular hypertrophy (LVH), patients were divided into LVH group and non LVH group for analyzing the influencing factors of cardiovascular disease. Patients were also divided into death group and survival group, peritoneal dialysis group and hemodialysis group based on the follow-up data for analyzing the prognostic factors. The chi-square test, independent sample t-test, Fisher exact probability test, Mann-Whitney U test and Kruskal Wallis test were used to analyze data among different groups. Multivariate Logistic regression analysis was used to identify the prognostic factors. Results: A total of 174 children with CKD5 were enrolled in the study (96 boys and 78 girls), aged 11.2 (8.2, 13.0) years. Congenital kidney and urinary tract malformations (CAKUT) were the most common causes of the CKD5 (84 cases, 48.3%), followed by glomerular diseases (83 cases, 47.7%), and among which 28 cases (16.1%) were hereditary glomerular diseases. The common complications of CKD5 included anemia (98.2%, 165/168), mineral and bone disorder in chronic kidney disease (CKD-MBD) (97.7%, 170/174), lipid metabolism disorders (87.5%, 63/72), hypertension (81.4%, 127/156) and LVH (57.6%,57/99). The incidences of hypertension in primary glomerular disease were higher than that in CAKUT(93.8%(30/32) vs.73.7%(56/76),χ2=5.59,P<0.05). The incidences of hypertension in secondary glomerular disease were higher than that in CAKUT and that in hereditary kidney disease (100.0%(20/20) vs. 73.7%(56/76), 68.2%(15/22), both P<0.05). The incidence of hypocalcemia in CAKUT, primary glomerular disease, and hereditary kidney disease was higher than that in secondary glomerular disease (82.1%(69/84), 88.2%(30/34), 89.3%(25/28) vs. 47.6%(10/21), χ2=10.21, 10.75, 10.80, all P=0.001); the incidence of secondary hyperparathyroidism in women was higher than that in men (80.0%(64/80) vs. 95.0%(57/60), χ2=6.58, P=0.010). The incidence of LVH in children aged 6-<12 was higher than that in children aged 12-18 (73.5%(25/34) vs. 43.1%(22/51), χ2=7.62, P=0.006). Among 113 follow-up children, the mortality rate was 39.8% (45/113). Compared to the survival group, the children in the death group had lower hemoglobin, higher blood pressure, lower albumin, lower alkaline phosphatase and higher left ventricular mass index ((67±19) vs. (75±20) g/L, 142 (126, 154) vs. 128(113, 145) mmHg(1 mmHg=0.133 kPa), (91±21) vs. (82±22) mmHg, 32 (26, 41) vs. 40 (31, 43) g/L, 151 (82, 214) vs. 215 (129, 37) U/L, 48 (38, 66) vs. 38(32, 50) g/m2.7,t=2.03, Z=2.89, t=2.70, Z=2.49, 2.79, 2.29,all P<0.05), but no independent risk factors were identified (all P>0.05). The peritoneal dialysis group had better alleviation for anemia, low calcium, and high phosphorus than the hemodialysis group ((87±22) vs. (72±16) g/L, (1.9±0.5) vs. (1.7±0.4) mmol/L, (2.2±0.7) vs. (2.8±0.9) mmol/L, t=2.92, 2.29, 2.82, all P<0.05), and the survival rate of the peritoneal dialysis group was significantly higher than that of the hemodialysis group (77.8% (28/36) vs. 48.4% (30/62), χ2=8.14, P=0.004). Conclusions: CAKUT is the most common etiology in children with CKD 5, and anemia is the most common complication. The incidence of complications in children with CKD 5 varies with age, gender and etiology. Anemia, hypertension, hypoalbuminemia, reduced alkaline phosphatase and elevated LVMI may be the prognostic factors in children with CKD5. Peritoneal dialysis may be more beneficial for improving the long-term survival rate.

[Follow-up analysis of sex hormone levels and prognosis in women after hematopoietic stem cell transplantation].

Objective: To investigate the levels of sex hormone and fertility in female patients after hematopoietic stem cell transplantation (HSCT), as well as their correlation with conditioning regimens, and analyse the effect of hormone replacement therapy (HRT) in young women after HSCT. Methods: Retrospective case series study. The clinical data of 147 women who underwent HSCT in the First Affiliated Hospital of Soochow University from January 2010 to January 2021 were retrospectively analyzed. The sex hormone levels were measured and followed-up, and the survival, menstrual fertility and the use of HRT of the patients were also followed-up. The sex hormone levels were measured after transplantation, and the ovarian function was evaluated. Independent sample t test and χ2 test were used for comparison between the two groups. Results: The median age of the 147 patients was 26 (range, 10-45) years. Of them, 135 patients received allogeneic HSCT and 12 patients received autologous HSCT. Furthermore, 129 patients received myeloablative conditioning, and 18 patients received reduced conditioning dose. The median follow-up time was 50 months (range, 18-134 months). Five patients died of disease recurrence during follow-up. Of the 54 patients with subcutaneous injection of zoladex, three recovered menstruation spontaneously after transplantation, and all of them were myeloablative conditioning patients, one patient gave birth to twins through assisted reproductive technology. Ninety-three patients did not use zoladex before conditioning, two patients with aplastic anemia with non-myeloablative transplantation resumed menstruation spontaneously, and conceived naturally. The level of follicle stimulating hormone after transplantation in patients receiving myeloablative conditioning regimen was significantly higher than that in patients receiving reduced-dose conditioning regimen [(95.28±3.94) U/L vs. (71.85±10.72) U/L, P=0.039]. Among 147 patients, 122 patients developed premature ovarian failure, 83 patients received sex hormone replacement therapy after transplantation, and 76 patients recovered menstruation and improved endocrine function. Conclusions: The incidence of premature ovarian failure is high in female patients after HSCT, and patients have a chance at natural conception. Reducing the dose of conditioning regimen and the application of zoladex before transplantation can reduce ovarian of conditioning drugs. HRT after transplantation can partially improve the endocrine function of patients.

Longitudinal Microbiome Changes in Supragingival Biofilm Transcriptomes Induced by Orthodontics.

INTRODUCTION: Common oral diseases are known to be associated with dysbiotic shifts in the supragingival microbiome, yet most oral microbiome associations with clinical end points emanate from cross-sectional studies. Orthodontic treatment is an elective procedure that can be exploited to prospectively examine clinically relevant longitudinal changes in the composition and function of the supragingival microbiome. METHODS: A longitudinal cohort study was conducted among 24 adolescent orthodontic patients who underwent saliva and plaque sampling and clinical examinations at time points: before fixed appliance bonding and at 1, 6, and 12 wk thereafter. Clinical indices included bleeding on probing (BOP), mean gingival index (GI), probing depths (PDs), and plaque index (PI). To study the biologically (i.e., transcriptionally) active microbial communities, RNA was extracted from plaque and saliva for RNA sequencing and microbiome bioinformatics analysis. Longitudinal changes in microbiome beta diversity were examined using PERMANOVA tests, and the relative abundance of microbial taxa was measured using Kruskal-Wallis tests, Wilcoxon rank-sum tests, and negative binomial and zero-inflated mixed models. RESULTS: Clinical measures of oral health deteriorated over time-the proportion of sites with GI and PI ≥1 increased by over 70% between prebonding and 12 wk postbonding while the proportion of sites with PD ≥4 mm increased 2.5-fold. Streptococcus sanguinis, a health-associated species that antagonizes cariogenic pathogens, showed a lasting decrease in relative abundance during orthodontic treatment. Contrarily, caries- and periodontal disease-associated taxa, including Selenomonas sputigena, Leptotrichia wadei, and Lachnoanaerobaculum saburreum, increased in abundance after bonding. Relative abundances of Stomatobaculum longum and Mogibacterium diversum in prebonding saliva predicted elevated BOP 12 wk postbonding, whereas Neisseria subflava was associated with lower BOP. CONCLUSIONS: This study offers insights into longitudinal community and species-specific changes in the supragingival microbiome transcriptome during fixed orthodontic treatment, advancing our understanding of microbial dysbioses and identifying targets of future health-promoting clinical investigations. KNOWLEDGE TRANSFER STATEMENT: Bonding braces was associated with subsequent changes in the oral microbiome characterized by increases in disease-associated species, decreases in health-associated species, and worsened clinical measures of oral health.

[Orodental phenotype and genotype findings in 8 Chinese children with hypophosphatasia].

Objective: To analyze the oral phenotype and gene variation of children with hypophosphatasia (HPP), and explore the genotype-phenotype correlations. Methods: Eight children diagnosed with HPP from January 2008 to January 2023 in Children's Hospital,Zhejiang University School of Medicine were recruited in this study. The pathogenic genes of 5 of them were sequentially analyzed and all of their oral manifestations, laboratory tests and genetic variation types were retrospectively analyzed. Results: A total of 8 children were recruited in the study, 3 males and 5 females, aged from 20 months to 104 months, whose main complaints were premature deciduous tooth loss. Among them, 3 children were diagnosed with odonto HPP, and the other 5 children were diagnosed with childhood HPP, including 2 children was odonto HPP at the first diagnosis and modified as childhood HPP at the age of 5. The age range of first deciduous tooth loss is 9 to 18 months, and the age range of diagnosis is 20 to 104 months. The patients of odonto HPP only showed premature loss of deciduous anterior tooth, while the patients with childhood HPP also showed premature loss of multiple deciduous molars. Panoramic radiographic film revealed enlarged pulp chambers and radicular canals in some primary and permanent teeth. The enamel hypoplasia, hypoplastic short roots, and alveolar resorption of deciduous molar were observed in some cases. The serum alkaline phosphatase (ALP) (30-107 U/L) levels of all the patients were lower than that in the normal children of same age and gender, and the ALP value of the 1-3 years old girls with childhood HPP (30-33 U/L) was lower than that of the three children with odonto HPP (61-107 U/L), but there was no significant difference in statistical analysis. There were 8 variation sites of ALP liver/bone/kidney (ALPL) gene detected in 5 children and their families, all of which were missense variation, including the new variants in the mutations of c.1334C>G(p.Ser445Cys) and c.1259G>T(p.Gly420Val) that were not reported in the literature. One case was autosomal dominant inheritance and other 4 cases were complex heterozygous variation with autosomal recessive inheritance. Conclusions: Pediatric stomatologists are often the first doctors to detect childhood and odonto HPP. Diagnosis of mild HPP is often delayed. The severity of HPP is related to serum ALP level and ALPL gene mutation sites.

[Hsa_circ_0000392 affects the radiation sensitivity of cervical cancer by targeting the miR-145-5p/CRKL/MAPK pathway].

Objective: To investigate the effect of hsa_circ_0000392 (circ_0000392) on the radiosensitivity of cervical cancer cells and explore its potential mechanism. Methods: Cervical cancer tissues and adjacent normal tissues of 42 patients with cervical cancer who were confirmed pathologically for the first time in Huaihe Hospital of Henan University from 2016 to 2019 were collected. According to the patients' response to radiotherapy, the cancer tissues were divided into radio-sensitive tissues and radio-resistant tissues. The expressions of circ_0000392, miR-145-5p, and CRKL in radiation-sensitive, radiation-resistant cervical cancer tissues and Hela, SiHa cells were detected by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. SiRNA circ_0000392, miR-145-5p mimic, miR-145-5p inhibitor, pcDNA 3.1-CRKL and its negative control were transfected into HeLa and Siha cells, respectively. After radiation induction, the survival fraction of cells was detected by clone formation assay, apoptosis was detected by flow cytometry, and the expressions of apoptosis-related proteins Bax and Bcl-2 and ERK pathway protein p-ERK1/2 and ERK1/2 were detected by western blot. The targeting relationship between circ_0000392, miR-145-5p and CRKL was verified by dual luciferase reporter gene assay. The effect of circ_0000392 on radiotherapy sensitivity of cervical cancer in vivo was observed in the tumor formation experiment in nude mice. Results: circ_0000392 and CRKL were upregulated in radiation-resistant tissues and cancer cells of cervical cancer, while miR-145-5p was downregulated. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ 6 Gy group were (78.67±10.97) and (71.00±9.54), respectively, which were lower than those in si-Ctrl+ 6 Gy group [(176.00±22.27) and (158.33±17.56), respectively]. The apoptosis rates were (41.55±3.40)% and (31.41±3.29)%, respectively, which were higher than those in si-Ctrl+ 6 Gy group [(15.91±1.37)% and (13.70±1.89)%, P<0.05]. The protein expression of Bax was higher than that of si-Ctrl+ 6 Gy group, and the protein expressions of Bcl2 was lower than those of si-Ctrl+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in si-circ_0000392#1+ miR-145-5p inhibitor+ 6 Gy group were (171.33±25.01) and (137.00±21.66), higher than those in si-circ_0000392#1+ inhibitor NC+ 6 Gy group [(84.67±17.79) vs (71.00±11.00), P<0.05]. The apoptosis rates were (17.41±2.58) % and (15.96±1.25) %, lower than those of si-circ_0000392 #1+ inhibitor NC+ 6 Gy [(40.29±2.92)% and (30.82±2.34)%, respectively, P<0.05]. The expression of Bax protein was lower than that of si-circ_0000392#1+ inhibitor NC+ 6 Gy group, and the expressions of Bcl2 protein were higher than those of si-circ_0000392#1+ inhibitor NC+ 6 Gy group. Circ_0000392 can target miR-145-5p, and CRKL is the downstream target gene of miR-145-5p. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ 6 Gy group were (74.33±10.02) and (66.00±12.17), respectively, which were lower than those of mimic NC+ 6 Gy group [(197.67±17.21) vs (157.67±11.59), respectively, P<0.05]. The apoptosis rates were (45.58±2.16)% and (32.10±3.55)%, higher than those of mimic NC+ 6 Gy group [(15.85±2.45)% and (13.99±1.69)%, respectively, P<0.05]. The expression of Bax protein was higher than that of the mimic NC+ 6 Gy mimic group, and the expression of Bcl2 protein was lower than that of the mimic NC+ 6 Gy group. The clone formation numbers of Hela and SiHa cells in miR-145-5p mimic+ pcDNA-CRKL+ 6 Gy group were (158.00±15.88) and (122.33±13.65), respectively, which were higher than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(71.33±8.02) vs (65.67±12.22), P<0.05]. The apoptosis rates were (19.50±3.45)% and (17.04±0.94)%, respectively, which were lower than those of miR-145-5p mimic+ pcDNA+ 6 Gy group [(44.33±2.36)% and (32.05±2.76)%, respectively, P<0.05]. The expression of Bax protein was lower than that of miR-145-5p mimic+ pcDNA group+ 6 Gy group, and the expression of Bcl2 protein was higher than that of miR-145-5p mimic+ pcDNA+ 6 Gy group. Sh-circ_0000392 group had smaller tumor volume and decreased tumor weight (P<0.05). The relative mRNA expression levels of circ_0000392, miR-145-5p and CRKL and the relative protein expression levels of CRKL, Bcl-2 and p-ERK1/2 were decreased, while the relative expression level of Bax protein was increased (P<0.05). Conclusion: Circ_0000392 could enhance the radiosensitivity of cervical cancer cells, and its mechanism may be related to the regulation of CRKL/ERK signaling pathway by targeting miR-145-5p, which provides a new reference for enhancing the radiosensitivity of cervical cancer cells.

[Shenqi Wenfei Formula alleviates chronic obstructive pulmonary disease in rats with pulmonary qi deficiency syndrome by regulating NLRP3/GSDMD pyroptosis pathway].

OBJECTIVE: To investigate the effects of Shenqi Wenfei (SQWF) Formula on the NLRP3/GSDMD signaling pathway in pulmonary qi deficiency syndrome rats with chronic obstructive pulmonary diseases (COPD). METHODS: Rat models of COPD and lung qi deficiency syndrome induced by exposure to cigarette smoke and lipopolysaccharide (LPS) injection were randomized (n=8) for treatment with low-, medium- and high-dose SQWF or Yu Ping Feng (YPF). The changes in body weight, grip strength, lung function, pulmonary pathology, peripheral blood inflammatory cell counts, and levels of inflammatory factors in the bronchoalveolar lavage fluid (BALF) were examined. The expressions of proteins associated with the NLRP3/GSDMD signaling pathway in the lung tissues were determined with RT-qPCR and immunohistochemistry. RESULTS: The rat models of COPD and lung qi deficiency syndrome showed significantly reduced body weight, grip strength and lung function (P<0.01) with severe lung pathologies, increased levels of WBC, NEU% and MON% (P<0.01), decreased LYM% (P<0.01), and increased levels of TNF-α, IL-6, IL-1ß and IL-18 in the BALF (P<0.01); the mRNA and protein expression levels of NLRP3, ASC, GSDMD and IL-1ß all increased significantly in the lung tissue (P<0.01). Treatment with SQWF and YPF obviously increased body weight and improved grip strength, pulmonary function and lung pathology of the COPD rats (P<0.05). The treatments obviously improved the changes in peripheral blood inflammatory cell counts and inflammatory factors in the BALF of the rat models (P<0.01) and lowered the expressions of NLRP3, ASC, GSDMD and IL-1ß in the lung tissues (P<0.05) without significantly affecting the mRNA levels of caspase-1 and IL-18 (P>0.05), and the effects of SQWF were dose-dependent. CONCLUSION: SQWF Formula relieves inflammatory response and injury in the lung tissue of COPD rats with pulmonary qi deficiency syndrome possibly by inhibiting pyroptosis through regulating the NLRP3/GSDMD pathway.

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia].

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

A prospective multicentre controlled study of Gaoweikang (Chinese multiherb extract-based tincture) used in high-risk HPV infections.

OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.

Efficacy of percutaneous cement-augmented screw fixation plus percutaneous kyphoplasty in the management of unstable osteoporotic vertebral compression fractures.

OBJECTIVE: The present study was performed to compare the efficacy of percutaneous kyphoplasty (PKP) vs. percutaneous cement-augmented screw fixation plus PKP in the management of unstable osteoporotic vertebral compression fractures (OVCF). PATIENTS AND METHODS: A total of 197 patients with unstable OVCF treated in the Department of Spine Surgery, Lianyungang First People's Hospital from September 2019 to September 2021 were recruited and assigned via random number table method 1:1 to receive either PKP (group A, n=106) or PKP plus percutaneous cement-augmented screw fixation (group B, n=91). The outcome measures for the evaluation of different surgical methods included visual analogue scale (VAS), the height of the anterior-posterior border of the injured spine, Cobb angle of the posterior convexity, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores. RESULTS: PKP exhibited shorter operative time and length of hospital stay and less intraoperative blood loss vs. PKP plus percutaneous cement-augmented screw fixation (p<0.05). Patients with PKP plus percutaneous cement-augmented screw fixation experienced milder postoperative pain vs. those with PKP alone at 7 days postoperatively, as evidenced by the lower VAS scores (p<0.05). PKP plus percutaneous cement-augmented screw fixation provided more restoration of anterior margin height and posterior convexity Cobb angle vs. PKP alone (p<0.05). Patients with PKP only showed slightly higher Japanese Orthopaedic Association (JOA) scores than those with combined surgery, while the postoperative clinical signs between the two arms were similar (p>0.05). CONCLUSIONS: Single PKP features the benefits of minimal trauma, simple operation, and rapid postoperative recovery in the treatment of OVCF. PKP plus percutaneous cement-augmented screw fixation for severe OVCF provided distinctly better performance than PKP alone in terms of early pain relief, restoration of vertebral body height, correction of posterior convexity deformity, and firm spinal stability.