Objective:To investigate therapeutic effect and mechanism of sanguinarine on postherpetic neuralgia(PHN)rats by modulating C-X-C chemokine ligand 12(CXCL12)/C-X-C chemokine receptor 4(CXCR4)signaling pathway.Methods:SD rats were randomly grouped into control group,model group,low-dose(50 mg/kg)sanguinarine group,high-dose(100 mg/kg)sanguina-rine group,NUCC-390(CXCL12/CXCR4 signal activator,2.2 mg/kg)group,high-dose(100 mg/kg)sanguinarine+NUCC-390(2.2 mg/kg)group,with 10 rats in each group.Rats in model group and drug-treated groups were injected with resin toxin(RTX)by intraperitoneal injection to induce PHN model,rats in control group were intraperitoneally injected with an equal dose of normal saline containing 10%Tween 80 and 10%ethanol.After treatment of sanguinarine and NUCC-390,symptoms of long-term spontaneous pain,mechanical hyperalgesia and thermal hyperalgesia were detected,number of spontaneous paw withdrawal reflexes,paw with-drawal threshold to mechanical stimulation(PWMT),and response latency to thermal stimulation(PWTL)were compared;spinal cord nerve cell apoptosis was detected by TUNEL staining;ELISA was used to detect levels of inflammatory factors TNF-α,IL-1β,cyclooxygenase-2(COX-2)in rat spinal cord tissue and serum;Western blot was used to detect expressions of CXCL12/CXCR4 path-way-related proteins in spinal cord tissues of rats in each group.Results:Compared with control group,PWMT of model group was obviously decreased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were obviously increased(P<0.05).Compared with model group,PWMT of rats in low-dose sanguinarine group and high-dose sanguinarine group was increased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were all decreased(P<0.05);PWMT of rats in NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Compared with high-dose sanguinarine group,PWMT of rats in high-dose sanguinarine+NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Conclusion:Sanguinarine can reduce expression of inflammatory factors by down-regulating CXCL12/CXCR4 signaling pathway,thereby preventing occurrence of inflammatory response in PHN rats,inhibiting apoptosis of spinal nerve cells,and finally reducing long-term spontaneous pain,mechanical allodynia and thermal hypoalgesia in rats.

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Objective:To investigate therapeutic effect and mechanism of sanguinarine on postherpetic neuralgia(PHN)rats by modulating C-X-C chemokine ligand 12(CXCL12)/C-X-C chemokine receptor 4(CXCR4)signaling pathway.Methods:SD rats were randomly grouped into control group,model group,low-dose(50 mg/kg)sanguinarine group,high-dose(100 mg/kg)sanguina-rine group,NUCC-390(CXCL12/CXCR4 signal activator,2.2 mg/kg)group,high-dose(100 mg/kg)sanguinarine+NUCC-390(2.2 mg/kg)group,with 10 rats in each group.Rats in model group and drug-treated groups were injected with resin toxin(RTX)by intraperitoneal injection to induce PHN model,rats in control group were intraperitoneally injected with an equal dose of normal saline containing 10%Tween 80 and 10%ethanol.After treatment of sanguinarine and NUCC-390,symptoms of long-term spontaneous pain,mechanical hyperalgesia and thermal hyperalgesia were detected,number of spontaneous paw withdrawal reflexes,paw with-drawal threshold to mechanical stimulation(PWMT),and response latency to thermal stimulation(PWTL)were compared;spinal cord nerve cell apoptosis was detected by TUNEL staining;ELISA was used to detect levels of inflammatory factors TNF-α,IL-1β,cyclooxygenase-2(COX-2)in rat spinal cord tissue and serum;Western blot was used to detect expressions of CXCL12/CXCR4 path-way-related proteins in spinal cord tissues of rats in each group.Results:Compared with control group,PWMT of model group was obviously decreased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were obviously increased(P<0.05).Compared with model group,PWMT of rats in low-dose sanguinarine group and high-dose sanguinarine group was increased(P<0.05),number of spontaneous foot withdrawal reflexes,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were all decreased(P<0.05);PWMT of rats in NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Compared with high-dose sanguinarine group,PWMT of rats in high-dose sanguinarine+NUCC-390 group was decreased(P<0.05),number of spontaneous foot withdrawal reflex,PWTL,spinal nerve cell apoptosis index,levels of TNF-α,IL-1β,COX-2 in spinal cord tissue and serum,and protein expressions of CXCL12 and CXCR4 in spinal cord tissue were increased(P<0.05).Conclusion:Sanguinarine can reduce expression of inflammatory factors by down-regulating CXCL12/CXCR4 signaling pathway,thereby preventing occurrence of inflammatory response in PHN rats,inhibiting apoptosis of spinal nerve cells,and finally reducing long-term spontaneous pain,mechanical allodynia and thermal hypoalgesia in rats.

Objective To investigate the impact of quercetin(Que)on postherpetic neuralgia(PHN)and chemokine ligand 3(CCL3,namely MIP-1α)/C-C chemokine receptor 1(CCR1)/C-C chemokine receptor 5(CCR5)signaling pathway in rats.Methods Sixty rats were divided into the control group(Con),the PHN group(model group),the L-Que(30 mg/kg)group,the M-Que(60 mg/kg)group,the H-Que(120 mg/kg)group and the H-Que+pathway activator MIP-1α(120 mg/kg Que+0.4 mg/kg recombinant MIP-1α)group.The mechanical paw withdrawal threshold(PWT)and thermal pain threshold(TWL)of rats were detected in each group.The kit was used to detect adenosine,Adenine ribonucleotide(AMP),adenosine diphosphate(ADP)and tumor necrosis factor in spinal dorsal horn samples-α(TNF-α),and interleukin-1 β(IL-1 β)levels in spinal dorsal horn samples.HE staining was applied to observe the pathological sections of spinal dorsal horn.Immunofluorescence staining was used to detect the activation of microglia in spinal dorsal horn.Western blot assay was applied to detect MIP-1α/CCR1/CCR5 signaling pathway protein expression.Results In the PHN group,the dorsal horn of the spinal cord was ruptured,the arrangement of nerve bundles was disordered,and inflammatory cell infiltration,edema,and slight atrophy of neurons appeared.Compared with the Con group,the PWT value,adenosine,AMP and ADP levels were obviously decreased in the PHN group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1-positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).After treatment with Que,the disordered arrangement of nerve bundles was improved,the infiltration of inflammatory cells was reduced,and the phenomenon of neuronal atrophy disappeared.Compared with the PHN group,the PWT value,adenosine,AMP and ADP levels were obviously increased in the L-Que group,the M-Que group and the H-Que group(P＜0.05).TWL value,TNF-αand IL-1β levels,the number of Iba1-positive microglia,and MIP-1α,CCR1 and CCR5 protein levels were obviously decreased(P＜0.05).The effect of Que was dose dependent.Compared with the H-Que group,PWT value,adenosine,AMP and ADP levels were obviously decreased in the H-Que+MIP-1α group(P＜0.05),and TWL value,TNF-α,IL-1β levels,the number of Iba1 positive microglia,MIP-1α,CCR1 and CCR5 protein levels were obviously increased(P＜0.05).Conclusion Que may reduce the inflammatory response in rats by inhibiting the MIP-1α/CCR1/CCR5 signaling pathway,thereby reducing PHN.

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Dysregulated Epiregulin(EREG)can activate epidermal growth factor receptor(EGFR)and promote tumor progression in head and neck squamous cell carcinoma(HNSCC).However,the mechanisms underlying EREG dysregulation remain largely unknown.Here,we showed that dysregulated EREG was highly associated with enhanced PDL1 in HNSCC tissues.Treatment of HNSCC cells with EREG resulted in upregulated PDL1 via the c-myc pathway.Of note,we found that N-glycosylation of EREG was essential for its stability,membrane location,biological function,and upregulation of its downstream target PDL1 in HNSCC.EREG was glycosylated at N47 via STT3B glycosyltransferases,whereas mutations at N47 site abrogated N-glycosylation and destabilized EREG.Consistently,knockdown of STT3B suppressed glycosylated EREG and inhibited PDL1 in HNSCC cells.Moreover,treatment of HNSCC cells with NGI-1,an inhibitor of STT3B,blocked STT3B-mediated glycosylation of EREG,leading to its degradation and suppression of PDL1.Finally,combination of NGI-1 treatment with anti-PDLl therapy synergistically enhanced the efficacy of immunotherapy of HNSCC in vivo.Taken together,STT3B-mediated N-glycosylation is essential for stabilization of EREG,which mediates PDL1 upregulation and immune evasion in HNSCC.

Objective:To explore the correlation between hypoalbuminemia and caspofungin-induced liver injury.Methods:This research was designed as a retrospective cohort study. The medical records of discharged adult patients treated with caspofungin acetate for injection (caspofungin) in Wuhan No.1 Hospital from January 1, 2019 to December 31, 2021 were extracted through the electronic medical record system. According to the average serum albumin level during caspofungin treatment, patients were divided into hypoalbuminemia group and non-hypoalbuminemia group. Propensity score matching (PSM) was performed for gender, age, weight, underlying disease, and hospital stay, etc. in a 1∶1 ratio in patients between hypoalbuminemia and non-hypoalbuminemia groups. Taking the occurrence of drug-induced liver injury as the outcome index, the incidences of liver injury were compared between the 2 groups, before and after PSM. The relative risk ( RR) and its 95% confidence interval ( CI) of caspofungin-related liver injury were calculated by cluster study method. Results:A total of 357 patients were entered, including 202 (56.6%) males and 155 (43.4%) females; 72 patients (20.2%) were in the hypoalbuminemia group and 285 patients (79.8%) were in the non-hypoalbuminemia group. Twenty-eight patients (7.8%) were judged with caspofungin-related liver injury, including 21 in the hypoalbuminemia group and 7 in the non-hypoalbuminemia group. The difference in the incidence of liver injury between the 2 groups was statistically significant whether before or after PSM [29.2% (21/72) vs. 2.5% (7/285), P<0.001; 29.2% (21/72) vs. 2.8% (2/72), P<0.001]. The results of the cluster study after PSM showed that hypoalbuminemia had a strong positive correlation with caspofungin-related liver injury ( RR=10.500, 95% CI: 2.555-43.143), and the incidence of caspofungin-related liver injury in patients with hypoalbuminemia was 26.39% higher than that in patients without hypoalbuminemia. Conclusion:Hypoalbuminemia was significantly correlated to the occurrence of caspofungin-related liver injury.

Objective:To explore the correlation between hypoalbuminemia and caspofungin-induced liver injury.Methods:This research was designed as a retrospective cohort study. The medical records of discharged adult patients treated with caspofungin acetate for injection (caspofungin) in Wuhan No.1 Hospital from January 1, 2019 to December 31, 2021 were extracted through the electronic medical record system. According to the average serum albumin level during caspofungin treatment, patients were divided into hypoalbuminemia group and non-hypoalbuminemia group. Propensity score matching (PSM) was performed for gender, age, weight, underlying disease, and hospital stay, etc. in a 1∶1 ratio in patients between hypoalbuminemia and non-hypoalbuminemia groups. Taking the occurrence of drug-induced liver injury as the outcome index, the incidences of liver injury were compared between the 2 groups, before and after PSM. The relative risk ( RR) and its 95% confidence interval ( CI) of caspofungin-related liver injury were calculated by cluster study method. Results:A total of 357 patients were entered, including 202 (56.6%) males and 155 (43.4%) females; 72 patients (20.2%) were in the hypoalbuminemia group and 285 patients (79.8%) were in the non-hypoalbuminemia group. Twenty-eight patients (7.8%) were judged with caspofungin-related liver injury, including 21 in the hypoalbuminemia group and 7 in the non-hypoalbuminemia group. The difference in the incidence of liver injury between the 2 groups was statistically significant whether before or after PSM [29.2% (21/72) vs. 2.5% (7/285), P<0.001; 29.2% (21/72) vs. 2.8% (2/72), P<0.001]. The results of the cluster study after PSM showed that hypoalbuminemia had a strong positive correlation with caspofungin-related liver injury ( RR=10.500, 95% CI: 2.555-43.143), and the incidence of caspofungin-related liver injury in patients with hypoalbuminemia was 26.39% higher than that in patients without hypoalbuminemia. Conclusion:Hypoalbuminemia was significantly correlated to the occurrence of caspofungin-related liver injury.

Objective:To investigate the treatment and prognosis of children with propionic acidemia (PA).Methods:This study involved 82 children with PA treated in the Department of Pediatric Endocrinol-ogy and Genetic Metabolism, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2002 to June 2020. Clinical data, including manifestations, laboratory test results, treatment strategy, and follow-up data, were summarized and analyzed using t-test or Mann-Whitney U test. Results:(1) Among the 82 cases consisting of 50 (61.0%) boys and 32 (39.0%) girls, 59 (72.0%) were diagnosed after clinical onset; 22 (26.8%) were diagnosed by newborn screening, including eight asymptomatic ones; the other one (1.2%) was asymptomatic but confirmed after the diagnosis of PA in the patient's sibling. The average age at first onset was 4.5 months (2 d-5 years) in 73 subjects, of which 28 (38.4%) were early-onset PA (within three months after birth). (2) Cranial MRI was performed on 26 cases, and abnormality was identified in 19 (73.1%) cases. (3) Hyperlactatemia was found in 16 cases among 30(53.3%) who underwent relevant examination with the average lactic acid level of 3.5 (2.1-4.3) μmol/L, while 35 out of 40 patients (87.5%) had hyperammonemia with an average blood ammonia level of 105.4 (34-907) μmol/L. (4) Among the 28 early-onset PA cases, 16 (57.1%) died, and 12 (42.9%) survived. There was no significant difference in the serum propionylcarnitine level, propionylcarnitine to acetylcarnitine ratio, urine 3-hydroxypropionic acid, or methylcitrate level between the survival and death cases. (5) Genetic mutations were detected in 75 patients (91.5%), among which 26 (34.7%) carried PCCA gene mutations and 48 (64%) with PCCB gene mutations. One patient (1.3%) harbored one known pathogenic mutation in each of the PCCA and PCCB genes. All mutations were inherited from the parents. (6) Followed up to June 2020, 57 (69.5%) patients survived, and 25 (30.5%) died from multiple organ failure secondary to severe acidosis, including 16 early-onset and nine late-onset cases. Conclusions:The primary treatment of PA is dietary control. Most PA patients are diagnosed after clinical onset, but symptoms may recur and even have developmental retardation despite treatment. Some of those diagnosed through newborn screening are asymptomatic after treatment. Newborn screening using tandem mass spectrometry is recommended for early diagnosis and treatment of PA.