Root caries is a prevalent chronic oral disease with an average global prevalence of 41.5%, characterized by high incidence, low rate of treatment, and high rate of retreatment. Root caries is primarily caused by core microbiome-induced dysbiosis and has multiple risk factors, including gingival recession, root surface exposure, and salivary dysfunction. The traditional preventive measures and treatments such as fluoride, mineralizing agents, and restorative materials, are unable to restore or maintain oral microecological homeostasis. Recent studies have demonstrated that probiotics, prebiotics, synbiotics, and antimicrobial peptides may prevent and treat root caries by reversing dysbiosis. In addition, these biotherapeutics can reduce acid production by acidiferous bacteria, promote alkali production (hydrogen peroxide and ammonia) by alkali-producing bacteria, inhibit biofilm formation, decrease extracellular polysaccharide production, and suppress microbial adhesion and aggregation. It is expected to play an important role in the prevention and control of root caries. This article aims to review oral probiotics (Streptococcus oligofermentans, Streptococcus oralis subsp. dentisani, and Streptococcus salivarius), prebiotics (arginine, nitrates, and synthetic compounds), synbiotics, and antimicrobial peptides (gallic acid-polyphemusin I and LH12) to provide evidence and guidance for root caries management through microecological modulation.

AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.

In the context of modern medicine,it's difficult for doctors lacking narrative thinking to get into the hearts of patients and offer high-quality medical service.Precise classification terms and decontextualized abstract language have become communication barriers between doctors and patients,creating an atmosphere of unusual indifference and fear during the medical process.William Osler,the father of modern medicine,emphasized that doctors should respect the individuality of patients,and advocated that doctors should use life-oriented language to provide humanistic care to patients.This echoes the concept of the"doctor-patient narrative community"in the construction of the Chinese narrative medicine system.As a brand new clinical humanistic practice path,narrative medicine focuses on the keyword"narrative"and revolves around the theme of"inter-subjective relationship"in the medical context,advocates that doctors switch flexibly in the two references of science and life,achieve visual fusion with patients and their families,pay attention to patients'life experiences,and establish narrative connections with them.On this basis,it can achieve two-way narrative interaction,build a harmonious doctor-patient narrative community,and thus enhance the patient's medical experience.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.

Objective:To analyze the clinical features, diagnosis, treatment and prognosis of nodular fasciitis (NF) in the head and neck.Methods:Seven cases of primary NF in the head and neck admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 1990 to 2022 were retrospectively analyzed, including 3 males and 4 females, aged from 2 to 67 years, and the location, course of disease, clinical manifestations, imaging findings, and treatment results of the disease were summarized.Results:Of the 7 patients, the primary sites were respectively nasal vestibule, paranasal sinus, nasal dorsum, sella turcica and clivus, neck, subglottis, and tonsil. Three cases presented with rapidly growing subcutaneous painless masses within 2 months, 1 case presented with hemoptysis, hoarseness and asthma for 28 days, 1 case presented with blood in the nasal discharge for 2 months, 1 case presented with headache for 1 month, and 1 case was found to have tonsillar neoplasms on physical examination for 3 days. CT was performed in 5 patients and the lesions showed soft tissue density shadows, and MRI was also performed in 2 of them, which showed T1 isointensity or T2 slightly long abnormal signal shadows. All patients underwent simple surgical resection of the mass. The patients were followed up for 13 months to 10 years, and none had recurrence.Conclusion:Primary NF in the head and neck is rare, with atypical clinical symptoms and imaging findings. Surgery is the mainstay of treatment for NF with good results.

Objective:To analyze the risk factors of hearing loss caused by neonatal cytomegalovirus (CMV) infection, to construct a nomogram prediction model, and to evaluate its discrimination and consistency.Methods:Data of a total of 250 neonates with congenital and perinatal CMV infection who were treated in our hospital from June 2018 to March 2021 were collected, and grouped into hearing-impaired group of 50 cases and hearing-unimpaired group of 200 cases according to whether the hearing was impaired or not. Logistic regression analysis was performed to analyze the risk factors affecting hearing loss caused by CMV infection in neonates. R software was applied to construct a nomogram model for predicting the risk of hearing loss caused by CMV infection in neonates, and the ROC curve and calibration curve were analyzed to verify the discrimination and consistency of the nomogram model.Results:Among 250 CMV-infected neonates in the modeling group, the incidence of hearing impairment was 20.00%. The proportion of primary maternal infection before 14 weeks of gestation, the proportion of urine CMV viral load >5×10 4 copies/ml, the proportion of symptomatic CMV infection and the proportion of abnormal head MRI in the hearing-impaired group were significantly higher than those in the hearing-unimpaired group ( χ2=12.545, 11.812, 11.801, and 9.025, P=0.000, 0.001, 0.001, and 0.003). That urine CMV viral load>5×10 4 copies/ml, symptomatic CMV infection and abnormal head MRI were the risk factors affecting hearing loss caused by CMV infection in neonates ( OR=2.388, 6.765, and 4.993, P=0.022, 0.000, and 0.001), the prediction model of the line graph was constructed using Bootstrap internal verification, Hosmer-Lemeshow goodness of fit test =6.055, P=0.301, area under ROC curve was 0.817, 95% CI=0.754~0.880, and external verification result showed that the predicted probability of the calibration curve was close to the actual probability and has a good agreement, with an AUC of 0.791 (95% CI=0.716~0.866). Conclusions:The nomogram model constructed in this study to predict the risk of hearing loss caused by CMV infection in neonates can be used for the prediction of hearing loss in neonates after CMV infection.

Objective:To investigate the efficacy and safety of ixazomib-based therapy for multiple myeloma.Methods:The data of 32 patients with multiple myeloma treated with isazomib-based regimen in the Affiliated Hospital of Jining Medical University from December 2020 to December 2021 were retrospectively analyzed. Among 32 patients, 17 cases were relapsed/refractory, and the remaining 15 cases had initial treatment. The treatment regimens included ID (isazomib + dexamethasone), IRD (isazomib + lenalidomide + dexamethasone) and ICD (isazomib + cyclophosphamide + dexamethasone). The short-term curative effect and adverse reactions of relapsed/refractory patients and patients at initial onset were analyzed.Results:The overall response rate (ORR) of relapsed/refractory patients was 52.9% (9/17), of which 6 cases achieved complete remission (CR), 2 cases achieved very good partial remission (VGPR) and 1 case achieved partial remission (PR). The ORR of refractory patients receiving bortezomib therapy was 40.0% (4/10). The ORR of patients at initial onset who could be evaluated the curative effect was 100.0% (14/14), including 9 cases of CR, 2 cases of VGPR and 3 cases of PR. After treatment, 2 patients (6.2%) had grade Ⅲ-Ⅳ adverse events (1 case of herpes zoster and 1 case of thrombocytopenia), and none of the patients had grade Ⅲ-Ⅳ peripheral neuropathy.Conclusion:Isazomib is effective and safe in the treatment of initially treated and relapsed/refractory multiple myeloma.

【Objective】 To explore the application of the indicator system of disease diagnosis related groups (DRGs) on the management of clinical blood use in hospitals. 【Methods】 Statistics information on clinical blood use as well as DRGs indexes including case mixed index (CMI), DRG grouping and corresponding weights among patients discharged during 2017 to 2019 from a hospital were recorded. RBC usage per 100 discharged patients after CMI adjustment and DRGs with a larger number of annual blood use cases were compared to make recommendations on the management of clinical blood use in the hospital. 【Results】 From 2017 to 2019, the number of blood users and patients discharged from our hospital kept growing, while the total blood use, RBC usage per 100 discharged patients after CMI adjustment showed a decreasing trend. There were 6 DRGs with the top five blood users from 2017 to 2019, and the top five DRGs accounted for 0.79%(5/629)in 2019, involving 1 611 blood use cases, accounted for 37.49%(1 611/4 297)of all cases of blood use in the year. 【Conclusion】 The application of the indicator system of DRGs to evaluate the clinical use of blood in hospitals is conductive to improve the rationality of clinical blood use, and can provide recommendations for the management of clinical blood use.

Objective To investigate the application prospect of the most extensive genome engineering pig internationally in preclinical xenotransplantation. Methods Porcine endogenous retrovirus (PERV) knockout combined with 3 major heterologous antigen gene knockouts and 9 humanized genes for inhibition of complement activation, regulation of coagulation disorders, anti-inflammatory and anti-phagocytosis were transferred into a pig (PERV-KO/3-KO/9-TG) as a donor, and the heart, liver and kidney were obtained and transplanted to 3 Rhesus macaque recipients respectively to establish a preclinical research model of pig-to-Rhesus macaque xenotransplantation. The functional status of xenografts after blood flow reconstruction was observed and the survival of recipients was summarized. The hemodynamics of xenografts were monitored. The change of hematological indexes of each recipient was compared. The histopathological manifestation of xenografts was observed. Results After the blood flow was reconstructed, all xenografts showed ruddy color, soft texture and good perfusion. The transplant heart, liver and kidney showed full arterial and venous blood flow and good perfusion at 1 d after operation. The postoperative survival time of heart, liver, and kidney transplant recipients was 7, 26, and 1 d, respectively. The levels of creatine kinase, creatine kinase isoenzyme, and lactate dehydrogenase increased in heart transplant recipient at 1 d after operation, and gradually recovered to near normal levels at 6 d after operation. All indexes increased sharply at 7 d after operation. The level of aspartate aminotransferase increased in liver transplant recipients at 2 d after operation, and the alanine aminotransferase basically returned to normal at 10 d after operation, but the total bilirubin continued to increase. Both aspartate aminotransferase and alanine aminotransferase increased at 12 d after operation, and reached a peak at 15 d after operation. The kidney transplant recipient developed mild proteinuria at 1 d after operation, and died of sudden severe arrhythmia. Histopathology showed that the tissue structure of cardiac and renal xenografts was close to normal, and liver xenografts presented with patchy necrosis, the liver tissue structure was disordered, accompanied by inflammatory damage, interstitial hemorrhage and thrombotic microangiopathy. Conclusions PERV-KO/3-KO/9-TG pig shows advantages in overcoming hyperacute rejection, mitigating humoral rejection and coagulation dysregulation. However, whether it can be used as potential donor for clinical xenotransplantation needs further evaluation.