AIM To investigate the ameliorative effects of Compound Fufangteng Mixture(CFM)on cyclophosphamide(CTX)-induced immunosuppression in mice.METHODS Forty-eight male C57BL/6J mice were randomly divided into the blank control group,the model group,the levamisole hydrochloride group(40 mg/kg)and the low-dose,medium-dose and high-dose CFM groups(3.75,7.5,10 g/kg),with 8 mice in each group,and given respective intervention orally once daily for 14 days.On the 5th to 7th day of administration,with the blank control group given normal saline intraperitoneally,the other groups underwent intraperitoneal CTX injections(80 mg/kg).24 hours after the last administration,organ indices of thymus and spleen were calculated;splenic histopathological alterations were assessed by HE staining;serum levels of IL-2,IL-6 and IgG were quantified using ELISA;splenic CD4+,CD8+T lymphocytes,alongside CD86+and CD206+macrophages populations were analyzed by flow cytometry;and splenic expression of CD4,CD8 and F4/80 was evaluated by immunohistochemical staining.RESULTS In CTX-treated mice,CFM administration mitigated body weight loss;enhanced thymus weight and thymic index;ameliorated splenic immune cell populations,elevated serum levels of cytokines IL-2,IL-6 and IgG in serum;and upregulated splenic levels of CD45+CD3+T lymphocytes and F4/80+CD11b+macrophages,alongside increasing the expression of CD4,CD8 and F4/80 surface markers.CONCLUSION CFM alleviates CTX-induced immunosuppression state in mice by modulating immune cells,restoring immune function and enhancing anti-inflammatory and tissue repair capabilities.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Background and purpose:Thyroid cancer is the most common malignant endocrine tumor,particularly prevalent among the Asian population.The overall survival for thyroid cancer patients is relatively high,but there are significant survival differences among patients.Based on long-term hospital-based cancer registry database,this study analyzed the 10-year observed overall survival(OS)rate of thyroid cancer cases and the distribution of causes of death,providing real-world evidences to further survival management of thyroid cancer in China.Methods:A total of 55343 thyroid cancer patients who underwent treatment at Fudan University Shanghai Cancer center from 2005 to 2021 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was October 31,2024.Kaplan-Meier method was applied in evaluating the OS rate,and survival data were described by different subgroups as age group,gender,treatment period,tumor staging and pathological characteristics.The standardized mortality ratio(SMR)and absolute excess risk(AER)were calculated using general Shanghai population as the reference,and the mortality risk was described by gender,age at diagnosis and histological subtype.Results:With a median follow-up time of 63.01 months,the overall 1-,3-,5-and 10-year OS rates of thyroid cancer patients were 99.67%(95%CI:99.62%-99.72%),99.11%(95%CI:99.03%-99.19%),98.48%(95%CI:98.36%-98.60%)and 95.81%(95%CI:95.50%-96.11%),respectively.The 10-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 97.99%(95%CI:97.70%-98.28%),89.80%(95%CI:87.24%-92.37%),77.84%(95%CI:70.76%-84.92%)and 62.95%(95%CI:55.37%-70.54%),respectively.The differences in OS among patients with different age,gender and histological classification were significant.1256(2.27%)deaths occurred,of which 18.63%,50.88%and 7.32%were attributable to thyroid cancer,other cancers and cardiovascular disease(CVD),respectively.Compared with the general population,patients with different subtypes of thyroid cancer had higher all-cause mortality rates,progressively increasing with papillary,follicular,medullary and anaplastic thyroid carcinoma/poorly differentiated carcinoma.Compared with general population,the death risk was 2.24 times higher in papillary thyroid cancer patients(95%CI:2.06-2.44),9.94 times higher in follicular thyroid cancer patients(95%CI:6.79-14.09),12.16 times higher in medullary thyroid cancer patients(95%CI:8.05-17.69),and the highest risk was observed in patients with anaplastic thyroid carcinoma/poorly differentiated carcinoma[SMR=79.67(95%CI:58.38-106.31),AER=766.01/1 000 person-years].Conclusion:The 10-year long survival data and cause of death for thyroid cancer patients with different histological types were reported in China based on a large single institution hospital-based cancer registry database.Staging and histological characteristics were the most important factors directly affected the survival.Early diagnosis and individualized treatment are crucial for improving prognosis.

With the establishment of bio-psycho-social medical model,both social and psychological factors play an important role in the occurrence,development and treatment of diseases.Hypertension is a common chronic multiple disease in China,and patients are often complicated with depression and other e-motional disorders.The interaction between hypertension and depression significantly increases the risk of poor prognosis.Current studies have shown a bidirectional promoting relationship between hypertension and depression,and they have some com-mon pathogenesis.However,the specific mechanism of their co-morbidity has not been fully elucidated.Renin-angiotensin sys-tem(RAS)plays an important role in the regulation of hyperten-sion and depression and other emotions.It is composed of two antagonistic pathways.The balance is maintained by angioten-sin-converting enzyme 2(ACE2).Therefore,this article reviews the relationship and mechanism of RAS in hypertension,depres-sion and comorbid states,in order to provide new treatment ide-as for hypertension and depression.

Objective:To explore the expression regulation of lipid metabolism gene ABHD5 in testes.Methods:Differential gene analysis was performed by integrating databases of TCGA and GTEx to identify the target gene ABHD5.The expression trends of ABHD5 gene in testicular carcinoma tissue were analyzed.Human testis single-cell atlases were obtained from the Human Protein Atlas and Male Health Atlas databases to determine the expression distribution of ABHD5 across different testicular cell types.Additionally,the GTEx database was utilized to visualize the expression pattern of ABHD5 in the testis,thereby enhancing the understanding of its transcriptional profile.The relationship between ABHD5 expression and age was assessed through integrated database analysis.Western blotting and immunofluorescence were performed to detect differential expressions of ABHD5 in testicular tissues of young and aged mice respectively.Results:The TCGA database indicated that the expression of ABHD5 in human testicular carcinoma tissue was significantly lower than that in normal testicular tissue which showed a negative correlation with patient survival.ABHD5 was highly ex-pressed in germ cells of the testis reveaked from Human Protein Atlas and Male Health Atlas databases.The stability of ABHD5 protein was crucial for testicular tissue,and its expression decreased with age.Furthermore,Western blot and immunofluorescence staining demonstrated that ABHD5 expression in the testicular tissue of aged mice was significantly lower than that in young mice.Conclu-sion:ABHD5 plays an important role in testicular tissue,and may be inseparable from testicular tumors and reproductive aging.How-ever,its mechanism of action remains to be further studied.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

Dental fluorosis is a chronic fluorosis manifestation characterized by tooth discoloration and structural abnormalities, resulting from excessive fluoride intake through respiratory and digestive systems during tooth development. This exposure inhibits ameloblast differentiation and disrupts enamel crystal formation and mineralization processes. While the exact pathogenesis remains unclear, this review systematically examines recent underlying mechanisms of dental fluorosis in the past five years, focusing on endoplasmic reticulum stress, Ca 2+ homeostasis imbalance, gene expression abnormalities, autophagy dysregulation, and microRNA-mediated regulatory pathways, in order to gain a deeper understanding of its pathogenesis at the molecular level and provide theoretical basis for prevention and treatment of dental fluorosis.

Objective:To observe the effect of modified autologous skull defect repair in patients with traumatic brain injury and its influence on neurological function and living ability.Methods:104 patients with traumatic brain injury who were admitted to our hospital from March 2022 to August 2024 were included,they were divided into Group A[37 cases,poly ether ether ketone(PEEK)skull defect repair],Group B(35 cases,traditional titanium mesh skull defect repair),and Group C(32 cases,modified autologous skull defect repair).Perioperative indicators,neurological function,activity of daily living,quality of life,satisfaction,and incidence of postoperative complications were compared among three groups.Results:There were no differences in the operation time,operation blood loss and postoperative hospital stay among the three groups(P＞0.05).The hospitalization costs of Group A,Group B and Group C decreased successively(P＜0.05).Activity of Daily Living(ADL)scores at 3 and 6 months after surgery increased among three groups,while National Institutes of Health Stroke Scale(NIHSS)scores decreased(P＜0.05).There was no significant difference in physiological function,social function,psychological function,and material life among the three groups at 6 months after surgery(P＞0.05).The overall satisfaction rate in Group C was higher than that of Group A and Group B(P＜0.05).The overall incidence of complications in Group C was lower than that in Group A and Group B(P＜0.05).Conclusion:PEEK,traditional titanium mesh,and modified autologous skull are used in skull defect repair,operation time,operation blood loss and postoperative hospital stay are comparable,they can also reduce neurological function damage,improve living ability,and enhance the quality of life of patients,however,PEEK is relatively expensive,the satisfaction of traditional titanium mesh is low,andincidence of postoperative complications are relatively high.

Objective:To observe the effect of modified autologous skull defect repair in patients with traumatic brain injury and its influence on neurological function and living ability.Methods:104 patients with traumatic brain injury who were admitted to our hospital from March 2022 to August 2024 were included,they were divided into Group A[37 cases,poly ether ether ketone(PEEK)skull defect repair],Group B(35 cases,traditional titanium mesh skull defect repair),and Group C(32 cases,modified autologous skull defect repair).Perioperative indicators,neurological function,activity of daily living,quality of life,satisfaction,and incidence of postoperative complications were compared among three groups.Results:There were no differences in the operation time,operation blood loss and postoperative hospital stay among the three groups(P＞0.05).The hospitalization costs of Group A,Group B and Group C decreased successively(P＜0.05).Activity of Daily Living(ADL)scores at 3 and 6 months after surgery increased among three groups,while National Institutes of Health Stroke Scale(NIHSS)scores decreased(P＜0.05).There was no significant difference in physiological function,social function,psychological function,and material life among the three groups at 6 months after surgery(P＞0.05).The overall satisfaction rate in Group C was higher than that of Group A and Group B(P＜0.05).The overall incidence of complications in Group C was lower than that in Group A and Group B(P＜0.05).Conclusion:PEEK,traditional titanium mesh,and modified autologous skull are used in skull defect repair,operation time,operation blood loss and postoperative hospital stay are comparable,they can also reduce neurological function damage,improve living ability,and enhance the quality of life of patients,however,PEEK is relatively expensive,the satisfaction of traditional titanium mesh is low,andincidence of postoperative complications are relatively high.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.