A real-world clinical study of immunocheckpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy in stage Ⅲ-ⅣA esophageal squamous cell carcinoma / 国际肿瘤学杂志

Objective:To investigate the efficacy of immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy for stage Ⅲ-ⅣA esophageal squamous cell carcinoma (ESCC) in the real world.Methods:The clinical data of 65 patients with stage Ⅲ-ⅣA ESCC treated by radical radiotherapy and chemotherapy from January 1, 2018 to December 31, 2022 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed. According to whether to undergo immune checkpoint inhibitor maintenance therapy after radical radiotherapy and chemotherapy, the patients were divided into a control group ( n=29) and an immune maintenance therapy group ( n=36) . The objective response rate (ORR) , progression-free survival (PFS) , and overall survival (OS) between the two groups were compared. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression model was used to conduct both univariate and multivariate analyses. Results:The ORR was 34.5% (10/29) in the control group and 61.1% (22/36) in the immune maintenance therapy group, with a statistically significant difference ( χ2=4.56, P=0.032) . The median PFS of control group and immune maintenance therapy group were 7.2 and 17.9 months, respectively, with a statistically significant difference ( χ2=7.86, P=0.005) . The median OS was 14.1 and 27.8 months, respectively, with a statistically significant difference ( χ2=5.40, P=0.020) . Univariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.28, P<0.001) and immune maintenance therapy ( HR=0.38, 95% CI: 0.17-0.88, P=0.024) were the influential factors of OS in ESCC patients treaded by radical chemoradiotherapy in stage Ⅲ-ⅣA. Multivariate analysis showed that, objective response ( HR=0.09, 95% CI: 0.03-0.29, P<0.001) and immune maintenance therapy ( HR=0.40, 95% CI: 0.17-0.92, P=0.032) were the independent influencing factors for OS in ESCC patients treaded by radical chemoracial therapy in stage Ⅲ-ⅣA. The incidence of adverse reactions was 22.22% (8/36) in the immune maintenance therapy group and 10.34% (3/29) in the control group, with no statistically significant difference ( χ2=1.61, P=0.204) . All the adverse reactions were grade 1-2, and the symptoms were relieved after symptomatic treatment. Conclusion:Maintenance therapy with immune checkpoint inhibitors after radical chemoradiotherapy of stage Ⅲ-ⅣA ESCC can significantly improve the prognosis of patients with good safety.

Computer Vision in Medical Imaging and its Impact on the Rare Musculoskeletal Diseases / 罕见病研究

There are over 6000 rare diseases in the world, affecting more than 300 million people. Early and precise diagnosis of rare diseases has always been the goal in clinical medicine. Emerging computer vision technology now greatly enhance medicine and healthcare and shows the potential in assisting the diagnosis and treatment for rare diseases. The technology can be a useful tool for extracting disease-relevant patterns from medical imaging. However, the effectiveness of its application depends on the complexity of the medical cases. In this paper, we summarize the challenges and emerging solution for the application of computer vision in diagnosis, rehabilitation as well as management of rare musculoskeletal diseases.

CT-Based Weighted Radiomic Score Predicts Tumor Response to Immunotherapy in Non-Small Cell Lung Cancer / 中国医学科学院学报

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.

Lumican and tumor therapy resistance / 国际肿瘤学杂志

Lumican is a member of the small leucine-rich proteoglycan family, which is involved in cell processes related to tumorigenesis and development, such as epithelial-mesenchymal transition, cell proliferation, migration, invasion and adhesion. The expression of Lumican in different tumors is positively or negatively correlated with tumor progression, and can be used as a reference for tumor prognosis and efficacy evaluation. Further study of the correlation and potential mechanism between Lumican and tumor therapy resistance can provide new ideas for predicting clinical therapeutic efficacy.

Value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting radiation pneumonitis in patients with esophageal cancer and lung cancer / 国际肿瘤学杂志

Objective:To investigate the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting the occurrence of radiation pneumonitis (RP) in patients with esophageal cancer and lung cancer.Methods:The clinicopathological data of 28 patients with esophageal and 16 patients with lung cancer undergoing radiotherapy from April 2018 to March 2020 in Hefei Cancer Hospital, Chinese Academy of Sciences were retrospectively analyzed, and the patients were divided into RP group ( n=16) and non-RP group ( n=28) according to whether RP occurred during and after treatment. The CD4/CD8 ratio and total B lymphocytes before radiotherapy between the two groups, and the CD4/CD8 ratio and total B lymphocytes before and after radiotherapy in the RP group were compared. Receiver operating characteristic curve was used to analyze the value of CD4/CD8 ratio and total B lymphocytes before radiotherapy in predicting RP. Results:The CD4/CD8 ratio before radiotherapy in the RP group was significantly lower than that in the non-RP group (0.993±0.179 vs. 1.708±0.170), with a statistically significant difference ( t=2.706, P=0.009); the total B lymphocytes in the RP group was significantly lower than that in non-RP group [(4.409±0.823)% vs. (8.153±1.017)%], with a statistically significant difference ( t=0.986, P=0.015). The CD4/CD8 ratio in the RP group was lower than that before radiotherapy when RP occurred (0.785±0.167 vs. 0.993±0.179), with no statistically significant difference ( t=1.376, P=0.189). The total B lymphocytes in the RP group was lower than that before radiotherapy when RP occurred [(3.487±1.018)% vs. (4.409±0.823)%], with no statistically significant difference ( t=0.804, P=0.433). The critical values of CD4/CD8 ratio and total B lymphocytes predicted RP were 0.580 and 0.357, respectively. The areas under the curve (AUC) of CD4/CD8 for predicting RP was 0.802 (95% CI: 0.653-0.932), the sensitivity was 89.29%, and the specificity was 68.75%. The AUC of total B lymphocytes for predicting RP was 0.694 (95% CI: 0.483-0.814), the sensitivity was 85.71%, and the specificity was 50.00%. The AUC of the two combined diagnostic method for RP was 0.834 (95% CI: 0.697-0.932), the sensitivity and specificity were 81.25% and 89.29%. AUC of the two combined tests was significantly higher than that of the single test, with statistically significant differences ( Z=1.115, P=0.046; Z=1.992, P=0.026). Conclusion:The CD4/CD8 ratio and total B lymphocytes in the RP group are lower than those in the non-RP group. The CD4/CD8 ratio and total B lymphocytes in the serum are of great significance in predicting the occurrence of RP in patients with malignant tumors receiving chest radiotherapy.

Development of novel self-adhesive resin cement with antibacterial and self-healing properties / 华西口腔医学杂志

OBJECTIVE@#This study aimed to develop novel self-adhesive resin cement with antibacterial and self-healing properties. Furthermore, the dentin bonding strength, mechanical properties, self-healing efficiency, and antibacterial property of the developed cement were measured.@*METHODS@#Novel nano-antibacterial inorganic fillers that contain quaternary ammonium salts with long-chain alkyls were synthesized. These fillers were added into self-adhesive resin cement containing self-healing microcapsules at mass fractions of 0, 2.5%, 5.0%, 7.5%, or 10.0%. The dentin shear bonding test was used to test the bonding strength, whereas the flexural test was used to measure the flexural strength and elastic modulus of the cement. The single-edge V-notched beam method was used to measure self-healing efficiency, and human dental plaque microcosm biofilms were chosen to calculate the antibacterial property.@*RESULTS@#The dentin shear bond strength significantly decreased when the mass fraction of the nano-antibacterial inorganic fillers in the novel cement reached 7.5% (P0.1). Resin cement containing 2.5% mass fraction or more nano-antibacterial inorganic fillers significantly inhibited the metabolic activity of dental plaque microcosm biofilms, indicating strong antibacterial potency (P<0.05).@*CONCLUSIONS@#The novel self-adhesive resin cement exhibited promising antibacterial and self-healing properties, which enable the cement to be used for dental applications.

Relationship between tuberculosis and microbiota / 中华实用儿科临床杂志

Tuberculosis(TB) caused by the Mycobacterium tuberculosis(Mtb) is a worldwide public health threat.Microbiota in body affects human health and is involved in human diseases, and its clinical importance is begi-nning to be understood.In this review, studies on the relationship between the establishment of Mtb infection and microbiota as well as the development and antibiotic treatment of Mtb infection were discussed.Studies have shown that: (1) microbiota influences the establishment of Mtb infection; (2) co-infection of Helicobacter pylori alters susceptibility to Mtb infection and progression of active TB; (3) microbiota influences the progression of TB by regulating the nutritio-nal, metabolic and immune status of the host; (4) susceptibility to reinfection increases in TB patients treated with antibiotics, possibly due to T-cell epitope depletion of common intestinal non-Mtb Mycobacterium, the effects of antibio-tics are long-term in patients; (5) the occurrence of childhood TB is age-related and many factors such as co-infection and vaccine inoculation increase risk.An in-depth study of the relationship between the microbiota and TB will provide a new perspective on the prevention of TB.

Regulatory effect of curcumin on renal apoptosis and its mechanism in overtraining rats / 中国应用生理学杂志

OBJECTIVE@#To study the effects and mechanisms of curcumin alleviating oxidative stress induced by overtraining and inhibiting renal apoptosis in rats.@*METHODS@#Male Wistar rats of 7 weeks old were divided into control group (C group, 12), overtraining group (OM group, 11), curcumin + overtraining group (COM group, 14). Group C did not undergo any exercise intervention. Rats in OM group and COM group underwent 8-week incremental load swimming training. During the training, the COM group was treated with curcumin at the dose of 200 mg/(kg·d) in the volume as 5 ml/kg by intragastric administration, and the other groups was treated with an equal volume of 0.5% carboxymethylcellulose. Twenty-four hours after the last training, renal histopathological changes were observed by light microscopy, related biochemical indicators in blood and renal tissue were detected.@*RESULTS@#The results showed that after 8 weeks of incremental load swimming training, the renal tissue structure of group C was normal under light microscope; histopathological changes were observed in OM group; COM group was significantly relieved compared with OM group. Compared with group C, serum levels of corticosterone (Cor), creatinine (Cr) and blood urea nitrogen (BUN) in OM group were increased (0.05), while the expression of heme oxygenase-1 (HO-1) was decreased (<0.05), total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity were decreased (<0.01), malondialdehyde (MDA) concentration was increased (<0.01); the renal apoptosis was increased (<0.01), the expression of anti-apoptotic B cell lymphoma-2 protein (Bcl-2) was decreased (<0.01), and the expression of proapoptotic Bcl-2 associated X protein (Bax) was increased (<0.01). Compared with the OM group, Cor level was decreased (<0.01) in the COM group, T level was increased (<0.01), Cr and BUN levels were lower (<0.05); the expression of Nrf2 and HO-1 were increased (<0.05), T-AOC and SOD activity were increased (<0.01), MDA concentration was decreased (<0.05); the renal apoptosis was decreased (<0.05), the expression of Bcl-2 was increased (<0.05), and the expression of Bax was decreased (<0.01). The trend of testosterone/corticosterone ratio between groups was consistent with testosterone change, and the change trend of Bcl-2/Bax ratio was consistent with the change of Bcl-2.@*CONCLUSIONS@#The 8-week incremental load swimming training triggered excessive training in rats, aggravated oxidative stress and accelerated renal apoptosis, leading to pathological changes and dysfunction of kidney. Curcumin can up-regulate expression of Nrf2 and HO-1, effectively alleviates oxidative stress induced by overtraining, thereby increasing Bcl-2 expression, decreasing Bax expression, inhibiting renal apoptosis and protecting renal tissue structure and function properly.

Cloning and expression analysis of tocopherol cyclase gene in Carthamus tinctorius / 中国中药杂志

The tocopherol cyclase was one of the key enzymes in plant vitamin E biosynthesis pathway. According to the study of Carthamus tinctorius transcriptome data,the Tocopherol cyclase gene was obtained using RT-PCR techniques and named CtTC . Bioinformatics analysis showed theopen reading frame （ORF）of CtTC was 1 524 bp. The putative protein contained 507 amino acids with a predicted molecular mass of 62.9 kDa and theoretically isoelectric point was 5.01.Signal peptide analysis showed that it was a non secretory protein, and there was no signal peptide. The subcellular localization showed that the CtTC protein was located in the chloroplast. The expression of CtTC gene in safflower seeds at different development stages was determined by quantitative real-time PCR, it was found that the highest expression level of CtTC gene was detected in 50 DAF.Quantitative RT-PCR analysis suggested that expression of CtTC is induced and strengthened by drought stresses. This research provided a candidate gene for metabolic engineering of vitamin E and resisting stress.

Effect of berberine on nitric oxide release of rat intestinal mucous microvascular endothelial cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of berberine on the release of nitric oxide (NO) by rat intestinal mucous microvascular endothelial cells (RIMECs) cultured in vitro for exploring the pharmacological mechanism of berberine in treating intestinal disease.</p><p><b>METHODS</b>Cultured RIMECs in vitro were identified adopting immunofluorescent stain with factor VIII-related antigen. NO level in the supernatant of normal cell culture or cell culture treated with different concentrations of berberine was detected with colorimetry at the 3rd, 6th, 9th and 12th h and compared.</p><p><b>RESULTS</b>Compared with that in the normal control group, NO level increased more obviously in the berberine treated groups, and the best effect was shown in the 5 microg/mL berberine treated group.</p><p><b>CONCLUSION</b>One of the important pharmacological mechanisms of berberine might be through promoting the endogenous NO release to induce endothelium-dependent dilatation of microvascular in intestinal mucosa, thus to improve the local microcirculation of intestine.</p>

Effect of electroacupuncture on expression of IFN-gamma-like immunoreactive substance in spinal cord of the rat / 中国针灸

<p><b>OBJECTIVE</b>To observe effect of electroacupuncture at "Zusanli" (ST 36) on expression of interferon-gamma (IFN-gamma)-like immunoreactive substance in spinal cord of the rat and to probe the mechanism.</p><p><b>METHODS</b>The IFN-gamma-like immunoreactive positive cell number in spinal cord of the rat was investigated with immunohistochemical SP method and microscopy.</p><p><b>RESULTS</b>After electroacupuncture at "Zusanli" (ST 36), IFN-gamma-like immunoreactive positive cell number in the spinal cord of the rat with electroacupuncture plus immunosuppression did not significantly change (P > 0.05). The number of positive cells in the dorsal horn in the rats with immunosuppression was significantly less than that in the normal control group (P < 0.05) with no significant change in other parts and with no significant difference between the electroacupuncture group and the control group (P > 0.05).</p><p><b>CONCLUSION</b>Electroacupuncture at "Zusanli" (ST 36) can increase expression of IFN-gamma-like immunoreactive substance in spinal cord of the rat, and acupuncture activates the nerve-immunoregulative network possibly by IFN-gamma as medium.</p>