Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate how deubiquitinase OTU domain-containing protein 3(OTUD3)suppresses the progression of hepatocellular carcinoma via gut-liver axis metabolic remodeling and microbiome dynamics.Methods A total of 24 male 2-week-old littermate C57BL/6J mice(12 wild-type and 12 Otud3-/-)were divided into two differential genotype groups before 6 mice from each group were randomly chosen to receive intraperitoneal injections of N-nitrosodieth-ylamine(DEN)for hepatocellular carcinoma(HCC)induction.The mice were divided into four groups(n=6/group):Otud3+/+control(WT CON),Otud3-/-control(KO CON),Otud3+/+DEN-induced HCC(WT DEN),and Otud3-/-DEN-induced HCC(KO DEN).At 40 weeks of age,liver tissues were collected for metabolomic profiling,and fecal samples were obtained for 16S rRNA sequencing.Results Multivariate analyses,including principal component analysis(PCA),partial least squares-discriminant analysis(PLS-DA),sparse partial least squares-discriminant analysis(sPLS-DA),and orthogonal partial least squares-discriminant analysis(OrthoPLS-DA),demonstrated complete intergroup separability.Fifty-four differential metabolites were identified between the WT DEN and KO DEN groups through metabolomic profiling,with gut-liver axis-associated pathways such as cholesterol metabolism and fatty acid biosynthesis revealed by KEGG pathway analysis.Microbiome analysis indicated an upregulation of Bacteroides at the genus level in the KO DEN group compared to WT DEN.Pearson correlation analysis highlighted amino acids and derivatives as predominant metabolite classes and revealed Bacteroidetes and Firmicutesas the dominant gut microbial phyla.Conclusion OTUD3 suppresses HCC progression by modulating gut-liver axis metabolism,potentially mediated by elevated betaine and increased abundance of Odoribacter,Alistipes,and Lachnoclostridium.

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians′ awareness of opportunistic virus reactivation during anti-tumor treatment.

This paper summarized the experience of fire needling combined with black cloth ointment in the treatment of keloid. In terms of the pathogenesis of keloid， it is believed that "phlegm causes stasis， and then stasis accumulates into tumors" is the key； the internal obstruction of phlegm and stasis caused by insufficient endowment and invasion of external pathogens is the root of the disease， while the endogenous generation of phlegm and dampness is the branch. It is therefore proposed to explore the etiology and pathogenesis of keloid from the perspective of "phlegm-stasis-tumor"， and the treatment principle is mainly to eliminate phlegm， dispel stasis and dissolve tumors， supplemented with heat-clearing and toxin-resolving. Treatment methods include oral administration of Chinese herbal medicinals and external treatment. Self-made formula for keloid is taken orally， with the main functions of dissolving phlegm， dispelling stasis and clearing heat， to finally dissolve the tumors. For external treatment， fire needling is used to pierce the skin and to open the striae and interstices， and force out the toxin pathogens such as phlegm-heat and stasis-heat with fire power， thereby clearing heat， dissolving phlegm， dispelling stasis and resolving toxins. Black cloth ointment can be used to the affected area to unblock meridians and collaterals， clear heat-toxin and dissolve phlegm-stasis， thereby softening hardness and dissipating masses.

Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.

Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P＜0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P＜0.01).The number of CD31 positive cells in the plaque were significantly decreased(P＜0.01),and the number of Vimentin positive cells were significantly increased(P＜0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P＜0.01),and HDL-C level was significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P＜0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P＜0.05,P＜0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P＜0.05,P＜0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P＜0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P＜0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P＜0.05,P＜0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P＜0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

Objective To explore the mechanism of Xinkang Prescription (Descurainiae Semen Lepidii Semen,Armeniacae Semen Amarum,Poria,Astragali Radix,Citri Reticulatae Pericarpium,Sparanii Rhizoma) for purging the lung and promoting diuresis in treating heart failure by regulating phosphorylation of phospholamban (PLN). Methods Forty-eight C57BL/6J mice were randomly divided into sham-operation group,model group,low-,medium-and high-dose Xinkang Prescription groups(0.455,0.91,1.82 g·kg-1),as well as Entresto group (25 mg·kg-1),with eight mice in each group. The model of ischemic heart failure was established by ligating the left anterior descending coronary artery in mice. After the model was successfully replicated,mice were orally administered with the above-mentioned dosages of Xinkang Prescription and Entresto once a day for four weeks,while sham-operation group and model group were given 0.9％ sodium chloride solution by gavage at the same time. Echocardiography was used to detect the cardiac function of the mice in each group,including left ventricular ejection fraction (LVEF),left ventricular fractional shortening (LVFS),left ventricular end-diastolic dimension (LVEDD) and left ventricular end systolic diameter (LVESD). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in cardiac tissue of mice. qRT-PCR was used to detect the mRNA expression of BNP. Western Blot and Jess were used to detect the expression of PLN,p-Thr17-PLN,p-Ser16-PLN,sarcoplasmic reticulum calcium ATPase 2a (SERCA2a),protein kinase A (PKA),p-PKA,Ca2+/calmodulin-dependent kinaseⅡ(CaMKⅡ) and p-CaMKⅡ in cardiac tissue,and to calculate the ratio of SERCA2a/PLN. The SERCA2a activity was determined by the inorganic phosphorus method.Results Compared with the sham-operation group,the model group showed a significant decrease in LVEF and LVFS(P<0.01) and a significant increase in LVEDD and LVESD (P<0.01). HE staining showed the fibril of cardiac muscle broke and disarranged,accompanied by inflammatory cell infiltration. The mRNA expression of BNP was significantly up-regulated (P<0.01),and the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly down-regulated (P<0.01),while the expression of p-CaMKⅡ was up-regulated (P<0.01). Compared with the model group,LVEF and LVFS in medium-,high-dose Xinkang Prescription groups were significantly increased(P<0.01),while LVEDD and LVESD were significantly decreased (P<0.01). HE staining showed significant improvement in the pathological damage of cardiac tissue. The expression level of BNP was significantly decreased (P<0.01),while the protein expressions of p-Ser16-PLN,p-Thr17-PLN,p-PKA,the ratio of SERCA2a/PLN and SERCA2a activity were significantly increased (P<0.01). The protein expression of p-CaMKⅡ was remarkably decreased(P<0.05). Conclusion Xinkang Prescription can effectively improve cardiac function of mice with heart failure,which may be related to enhance phosphorylation levels of phospholamban.

Objective To understand the relationship between air pollutants and digestive system cancers, and to provide a reference for future research and prevention and control of digestive system cancer. Methods All relevant literature published in English between 1970-2022 was searched through the databases of PubMed, web of science and Embase, and meta-analysis was used to explore the effects of specific air pollutants on digestive system cancers. Results PM_2.5 was able to increase the risk of incidence or mortality of total digestive cancers by 11% (1.05 to 1.17). For specific cancers, PM_2.5 was only associated with an increased risk of liver cancer in this study, with a combined RR (95% CI) of 1.31 (1.19 to 1.46), while there was no statistically significant association with other specific digestive cancers ( P>0.05）. NO2 increased the risk of incidence or mortality of total digestive cancers by 3% (1.00 to 1.07). Conclusion For specific digestive system cancers, PM_2.5 has the most pronounced effect on liver cancer. More evidence is needed to support the relationship between NO₂ and cancer. Currently, it has been observed that NO2 has a negative effect on overall digestive cancers. This study provides insights for the prevention and control of digestive system cancer in countries and regions with high PM_2.5 and NO₂ concentrations.

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

Based on the theory of ascending and descending of center qi， it is believed that yang deficiency and water dampness， as well as abnormal circulation of center qi， are the core pathogenesis of psoriasis. The common pathogenic evolution of psoriasis includes wood constraint and blood stagnation， lung metal fluid exhaustion. In the later stage of psoriasis， a mixture of deficiency and excess patterns， as well as cold and heat in complexity， are often observed. Treatment focuses on warming yang and resolving dampness to restore proper qi ascending and descending， and the therapeutic formulas such as Ganjiang Lingzhu Decoction （甘姜苓术汤）， Zexie Decoction （泽泻汤）， Zhenwu Decoction （真武汤）， and Linggui Zhugan Decoction （苓桂术甘汤） are suggested based on the nature and location of the disease. To unblock the qi movement through discharging the liver and rectifying the lung， Xiaochaihu Decoction （小柴胡汤） and Danzhi Xiaoyao Powder （丹栀逍遥散） are commonly used as the foundation with modifications. To balance yin and yang through clearing the heart and nourishing the kidneys， a self-designed Changzhong Decoction （畅中汤） is utilized. Following the theory of ascending and descending of center qi， it is suggested to combine cold and warm medicinals and mediate the center earth， so as to promote the circulation of the center qi， restore the clear and the turbid， and keep four-dimensional smooth flow of qi， providing a reference for traditional Chinese medicine treatment for psoriasis.