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.

Knee osteoarthritis(KOA)and osteoporosis(OP)"co-morbidity"is a chronic progressive disease,the incidence of which is higher in recent years.Exosomes have intercellular messenger functions,which play an important role in the development of KOA and OP"co-morbidity".This article recognized the"co-morbidity"between KOA and OP from the perspective of modern medicine and the"tendon","bone","liver"and"kidney"in TCM theories,systematically reviewed the indirect regulation of KOA and OP"co-morbidity"through exosomes,and explored the possible mechanisms of exosome-based treatment of KOA and OP"co-morbidity"through Chinese materia medica in terms of inflammation,MAPK pathway,bone remodeling and cartilage metabolism,and mitochondrial autophagy,with the aim to investigate the possible mechanisms of KOA and OP"co-morbidity",and provide new ideas for the treatment of KOA and OP"co-morbidity".

OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.

Knee osteoarthritis(KOA)and osteoporosis(OP)"co-morbidity"is a chronic progressive disease,the incidence of which is higher in recent years.Exosomes have intercellular messenger functions,which play an important role in the development of KOA and OP"co-morbidity".This article recognized the"co-morbidity"between KOA and OP from the perspective of modern medicine and the"tendon","bone","liver"and"kidney"in TCM theories,systematically reviewed the indirect regulation of KOA and OP"co-morbidity"through exosomes,and explored the possible mechanisms of exosome-based treatment of KOA and OP"co-morbidity"through Chinese materia medica in terms of inflammation,MAPK pathway,bone remodeling and cartilage metabolism,and mitochondrial autophagy,with the aim to investigate the possible mechanisms of KOA and OP"co-morbidity",and provide new ideas for the treatment of KOA and OP"co-morbidity".

To investigate the effect of mitochondrial division inhibitor 1(Mdivi-1)on imiquimod(IMQ)-induced psoriasis-like skin inflammation in mice and its mechanism,female 8-week-old C57BU6 mice were recruited and randomly divided into control group,IMQ model group,IMQ+Mdivi-1 experiment group.IMQ was used to induce the psoriasis-like skin inflammation model in mice.The mice in the experiment group were injected intraperitoneally(i.p.)with Mdivi-1,and the mice in the control group and model group were injected with the same volume of solvent.The mice were sacrificed on the 7th day for sampling.Psoriasis area and severity index(PASI)score was used to evaluate the severity of skin lesions in each group;the reactive oxygen species(R0S)content in skin tissue was detected by fluorescence staining of frozen section;HE staining was used to observe the histomorphologic change of skin lesions;immunohistochemical staining was used to detect the expression of dynamin-related protein 1(Drp1)in the skin of mice;Western blot was used to detect the protein levels of Drp1,NLRP3 and IL-1β in the skin tissues of mice in each group;and the expressions of IL-17A and IL-18 in mouse serum were detected by ELISA.Data showed that the model group had typical psoriatic lesions such as erythema,scale and thickening,and the Mdivi-1 group demonstrated obvious reduction of the lesions.The PASI score of the experiment group was significantly lower than that of the model group.HE staining indicated that the epidermal thickness of the back skin in the treatment group was significantly lower than that in the model group,and Munro microabscess was significantly reduced.R0S fluorescence staining indicated that ROS content in the experiment group was significantly lower than that in the model group;immunohistochemical results showed that the expression of Drp1 protein in the experiment group was significantly lower than that in the model group;Western blot results showed that the expression levels of Drp1,NLRP3 and IL-1 β in the experiment group were significantly lower than those in the model group;ELISA results indicated that the expressions of IL-17A and IL-18 in serum of mice in the experiment group were lower than those in the model group.Taken together,Mdivi-1 can reduce mitochondrial damage and ROS production by inhibiting the expression of Drp1,thereby reducing the production of NLRP3 inflammasome,down-regulating IL-1 β,IL-18 and IL-17A,and alleviating the IMQ-induced psoriasis-like skin inflammation in mice.

Objective To analyze the relationship between glutathione S-transferase P1 (GSTP1) 313A＞G polymorphism and the adverse reactions induced by cyclophosphamide (CP). Methods The clinical research literature about the relationship between GSTP1 313A＞G polymorphism and the adverse reactions induced by CP were collected from related domestic and foreign databases up to July,2017. The quality of the literature was evaluated by STREGA criterion. The meta-analysis was conducted by RevMan 5.2 software and the results were expressed as relative risk (RR)and 95% confidence interval (CI). Results A total of 7 articles were included in the meta-analysis and their quality evaluation results were reliable (all scores≥3),involving 1 305 patients. The results of meta-analysis showed that the differences of incidence of leukopenia,neutropenia,anemia,thrombocytopenia,myelosuppression,and infection after the treatments of CP combined with other chemotherapeutics between the patients with GSTP1 313A＞G AA genotype and GSTP1 313A＞G AG/GG genotype were not statistically significant (P＞0.05 for all);the incidence of gastrointestinal reactions in patients with GSTP1 313A＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞AG/GG genotype (RR＝0.46,95%CI:0.22-0.97,P＝0.004);the incidence of myelosuppression after the treatment of CP alone in patients with GSTP1 313A ＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞G AG/GG genotype (RR＝0.27, 95%CI:0.08-0.91,P＝0.03). Conclusion The gastrointestinal reactions induced by CP combined with other chemotherapeutics and myelosuppression induced by CP alone may be related to the polymorphism of GSTP1 313A＞G.

Objective To analyze the relationship between glutathione S-transferase P1 (GSTP1) 313A＞G polymorphism and the adverse reactions induced by cyclophosphamide (CP). Methods The clinical research literature about the relationship between GSTP1 313A＞G polymorphism and the adverse reactions induced by CP were collected from related domestic and foreign databases up to July,2017. The quality of the literature was evaluated by STREGA criterion. The meta-analysis was conducted by RevMan 5.2 software and the results were expressed as relative risk (RR)and 95% confidence interval (CI). Results A total of 7 articles were included in the meta-analysis and their quality evaluation results were reliable (all scores≥3),involving 1 305 patients. The results of meta-analysis showed that the differences of incidence of leukopenia,neutropenia,anemia,thrombocytopenia,myelosuppression,and infection after the treatments of CP combined with other chemotherapeutics between the patients with GSTP1 313A＞G AA genotype and GSTP1 313A＞G AG/GG genotype were not statistically significant (P＞0.05 for all);the incidence of gastrointestinal reactions in patients with GSTP1 313A＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞AG/GG genotype (RR＝0.46,95%CI:0.22-0.97,P＝0.004);the incidence of myelosuppression after the treatment of CP alone in patients with GSTP1 313A ＞G AA genotype was significantly lower than that in patients with GSTP1 313A＞G AG/GG genotype (RR＝0.27, 95%CI:0.08-0.91,P＝0.03). Conclusion The gastrointestinal reactions induced by CP combined with other chemotherapeutics and myelosuppression induced by CP alone may be related to the polymorphism of GSTP1 313A＞G.

Objective To cxplore the variation of the range of motion (ROM) of operative level after different heights of artificial cervical disc replacement,and to provide guidance for clinical work in selecting appropriate height of artificial cervical disc prosthesis.Methods The preoperative cervical anteroposterior and lateral Ⅹ-rays of 9 fresh male cadaveric cervical spine specimens were obtained to measure the intervertebral height of C5-6,and 3 screened specimens with the height of about 5 mm were included in the experiment.The experiment was designed to test self-control,and other four groups of cervical specimens including intact group,appropriate height (5 mm) of C5.6 artificial cervical disc replacement group,1mm increased (6 mm) group and 2 mm increased (7 mm) group were made biomechanical test sequentially.The specimens were fixed to the cervical three-dimensional movement machine,with a 75 N follower load and pure moments of 2 Nm for flexion/extension 、left/right bending and left/right axial rotation,to measure the ROM of operative level under the condition of changes in 0.2 Nm/s.Results There were no significant differences in the ROM of flexion/extension,lateral bending and axial rotation between 5 mm group and intact group;the ROM of flexion/extension、lateral bending and axial rotation in 6 mm group increased compared with 5 mm group,but the difference was not statistically significant;the ROM of flexion/extension in 7 mm group was significantly less than that of intact,5mm and 6 mm group (9.5°± 1.0° vs 12.5°±0.9°、11.3°±0.8°、11.6°±0.9°),but significantly greater in axial rotation than 6 mm group (10.4°±1.4°vs 8.6°±0.3°),and there was no significant difference in lateral bending compared with other 3 groups.Conclusion 2 adjacent heights of cervical disc prostheses are implantedsuitably when testing the mold of disc prosthesis,the choice of cervical disc prosthesis with 1 mm increased can improve the ROM of operative level to some extent;while the height with 2 mm increased can lead to the ROM of flexion/extension at the operative level reduced,but the ROM of rotation shows an increasing trend.

OBJECTIVE:To investigate the role of clinical pharmacists in the therapy for patient with multiple pulmonary in-fection after renal transplantation. METHODS:Clinical pharmacists participated in drug therapy for a patient with multiple pulmo-nary infection after renal transplantation,and assisted physicians to formulate primary therapy plan:ganciclovir 250 mg,ivgtt,q12 h+ Cefoperazone sodium and sulbactam sodium 3 g,ivgtt,bid+ methylprednisolone 80 mg,ivgtt,qd+ Compound sulfamethoxazole tablet,2 piece,po,qd+Ciclosporin soft capsule 75 mg,po,q12 h+Sodium bicarbonate tablet 1 g,po,qd+Nifedipine controlled release tablet 30 mg,po,qd+Famotidine tablet 20 mg,po,bid. The dose of ganciclovir was adjusted twice because of complica-tion cytomegaloviral pneumonia;the dose of ganciclovir was adjusted twice because of complication pneumocystis pneumonia. Pre-vention and disposal of ADR,patient education were also conducted. RESULTS:Physicians adopted the suggestion of clinical phar-macists;the pulmonary infection had been controlled,and the patient was discharged from hospital. CONCLUSIONS:Clinical pharmacists identify the breakthrough point to promote rational drug use,indicating the value of pharmaceutical care in the clinical treatment.

Objective To design and construct a controlled adenovirus vector in degradating by itself after induction for solving the problem of stimulating host immune and producing replication adenovirus and providing a secure exogenous gene vectors for clinical practice. Methods Based on the traditional adenovirus vector AdEasyTM system, we inserted the Cre gene which belongs to Cre-LoxP system into the downstream of Tet-On inducible expression system. Two LoxP sites were inserted into two sides of the shuttle plasmid′s right arm genome. Then, the full-length human insulin gene was inserted HindIII enzyme site. After the recombinant adenovirus infected the rat bone marrow-derived mesenchymal stem cells , fluorescent protein expression and insulin secretion were detected before or after induction by Dox. Results A new controlled recombinant adenovirus vector carrying human insulin gene was constructed successfully, and was named AdEasyN/INS. After the transfection of this new vector into QBI-293A cells and rat bone marrow mesenchymal stem cells , green fluorescent protein could be observed. After induction by Dox, both of the ratio of fluorescent cells/total cell and the levels of insulin significantly decreased. Conclusion Construction and preliminary validation of a controlledrecombinant adenovirus vector carrying human insulin gene is constructed successfully , it could infect rat bone marrow mesenchymal stem cells, and degradate by itself after Dox induction, realize the controllability of exogenous gene carrier.