Objective:To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China.Methods:From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children′s Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases.Results:A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M ( Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant ( P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion:The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

Objective:To investigate the genotype and epidemiological characteristics of human metapneumovirus (HMPV) among hospitalized cases with acute respiratory infections (ARI) in children in Changchun City, Jilin Province, China.Methods:From June 2019 to June 2023, throat swabs of ARI inpatients in Changchun Children′s Hospital were collected, and their epidemiological and clinical information were also collected. Quantitative reverse transcription-PCR was used to identify HMPV-positive cases, followed by the amplification of the G gene and genetic analysis in the HMPV-positive cases.Results:A total of 3 311 children hospitalized with ARI were included in this study. Their age ranged from 0 to 17 years old, and the M ( Q1, Q3) of age was 2 (1, 3) years. About 1 811 (54.70%) cases were males. A total of 167 HMPV-positive cases were detected with a positive rate of 5.04%, of which 92.81% (155/167) were children under 5 years old. The positive rate of HMPV in 2019 was 6.37% (30/471), which dropped to the lowest in 2020 (2.31%, 10/432). The HMPV-positive rate was then rebounded in 2021 (4.70%, 60/1 277) and 2022 (4.56%, 21/461), which increased to 6.87% (46/670) in 2023. The difference in HMPV-positive rate among each year was statistically significant ( P<0.05). The prevalence peak of HMPV varied in different years, showing either a unimodal or bimodal distribution in one year. A total of 79 HMPV G gene sequences were obtained, of which subtype A and subtype B accounted for 48.10% and 51.90%, respectively. All of the subtype A sequences were clarified as A2c duplicated variants, and subtype B was mainly B2 genotype. Besides, subtypes A and B were prevalent alone or co-circulated in different years, and there was a subtype replacement pattern in HMPV. Conclusion:The positive rate of HMPV in hospitalized ARI cases in children is significantly different from 2019 to 2023 in Changchun City. Notably, there are certain switch patterns of HMPV subtypes A and B in different years.

Objective:To explore the clinical effects of parallel combined flow-through perforator flaps in the treatment of circular hot crush injuries in limbs with blood supply disorder.Methods:The study was a retrospective observational study. From April 2016 to December 2022, 4 cases with circular hot crush injuries in limbs with blood supply disorder were admitted to the Department of Burns and Plastic Surgery of the 988 th Hospital of Joint Logistics Support Force of PLA, including 3 males and 1 female, aged from 24 to 48 years. Among them, 2 cases were injured in the calf and 2 cases were injured in the forearm. After emergency debridement, the area of skin and soft tissue defects was from 20 cm×20 cm to 44 cm×20 cm. The patients had defects in tibialis anterior and posterior tibial arteries with a length of 13 to 18 cm, and in ulnar and radial arteries with a length of 9 to 12 cm. Flaps were designed and cut, including a flow-through anterolateral thigh perforator flap with area of 20 cm×9 cm to 24 cm×21 cm carrying the descending branch of the lateral circumflex femoral artery and the accompanying veins of 8 to 18 cm in length; and a flow-through posterior tibial artery perforator flap with area of 21 cm×13 cm and 20 cm×14 cm carrying the posterior tibial artery, the accompanying veins with a length of 14 and 17 cm respectively, and the great saphenous vein with a length of 22 and 21 cm. The circular hot crush injury wounds in the calf with blood supply disorder were repaired by a parallel combination of flow-through posterior tibial artery perforator flap and flow-through anterolateral thigh perforator flap, and the circular hot crush injury wounds in the forearm with blood supply disorder were repaired by a parallel combination of bilateral flow-through anterolateral thigh perforator flap, and the injured main vessels were reconstructed. The donor site wounds of flap were closed directly or treated with split-thickness skin grafts from abdomen. After surgery, the blood supply and survival of the flap and distal affected limb, the healing of wounds in the donor and recipient sites, the survival of the skin graft in the flap donor site were observed. During follow-up, the condition of flaps, the appearance, blood supply, and function of affected limbs were observed. At the last follow-up, the foot and ankle functions were evaluated according to the scoring standards of American Orthopedic Foot and Ankle Association, and the wrist and hand function was evaluated according to the trial standard of replantation of amputated upper limb function assessment of the Hand Surgery of Chinese Medical Association. Results:The flaps and distal affected limbs of 4 patients had good blood circulation and successfully survived after surgery. The wounds of 3 cases successfully healed, while one patient with circular hot crush injury in the forearm experienced exudation in the recipient site in the later stage, and the wound healed after re-expansion and suturing. The donor site wounds healed smoothly, and the skin grafts successfully survived. During follow-up of 12 to 24 months after surgery, the flaps were slightly swollen, the limbs had good appearance, normal blood circulation, and fine functional recovery. At the last follow-up, the foot and ankle function of 2 patients with circular hot crush injuries in the calf was evaluated as good in 1 case and commonly in 1 case; the wrist and hand function of 2 patients with circular hot crush injuries in the forearm was evaluated as excellent in 1 case and good in 1 case.Conclusions:The parallel combined flow-through perforator flap can reconstruct the damaged main blood vessels and repair the wound at the same time. It can not only effectively save the limb, but also restore part of the function of the affected limb. It is one of the effective methods to treat the circular hot crush injuries in limbs with blood supply disorder.

In order to achieve the purpose of rapid detection of duck astrovirus type 1(DAstV-1),specific primers were designed based on the conservative region of ORF1a which belonged to DAstV-1(WF1202 strain).A real-time fluorescent quantitative PCR(qPCR)detective method for DAstV-1 was established.Clinical samples were detected by the qPCR method and the positive samples were used for virus isolation and identification.Results showed that the detection limit of the established method was 4.64×103 copies/μL,which was 10 times higher than the normal RT-PCR method.In addition,no cross-reactions were found with other common infectious disease pathogens in poultry,indicating that the qPCR method had good specificity.What's more,the coef-ficient of variations(Cv)in intra-and inter-assays were 0.85％-2.85％and 0.21％-2.94％,re-spectively,both less than 3％,indicating that the qPCR method had a good repeatability.Using this method,35 tissue samples from different duck farms in 10 provinces from 2020 to 2022 were detected for DAstV-1.Results showed that the positive rate was 25.71％(9/35),and the coinci-dence rate was 94.29％when compared with the normal RT-PCR method.A positive sample ran-domly taken for the virus isolation through duck embryo passage,and the allantoic fluid was col-lected and then was verified by the qPCR method and inoculated with 1-day-old healthy ducklings for the animal regression experiment.The infected ducklings suffered from transient disease but did not die.The liver tissues were all positive with DAstV-1 when detected by qPCR.Meanwhile,autopsy showed that there were slight changes in the livers,and the histopathological observation showed that the liver cells were steatosis.These findings indicated that the isolated DAstV-1 strain had weak pathogenicity and might be a low virulent strain.To sum up,the qPCR detection method of DAstV-1 was successfully established in this work,and could provide technical support for clini-cal diagnosis,isolation and identification,and molecular epidemiology monitoring of DAstV-1.

Objective:To analyze the clinical efficacy of debridement, antibiotics irrigation and implant retention (DAIR) in the treatment of acute periprosthetic infection (PJI) and to explore the risk factors leading to the failure of DAIR.Methods:From January 2010 to January 2021, 122 patients underwent DAIR for acute PJI at Department of Orthopedics, General Hospital of Eastern Theater of PLA. They were 55 males and 67 females, aged from 50 to 86 years (mean, 68.0 years). Their C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), body temperature, white blood cell count and visual analogue scale (VAS) were compared at admission and discharge to analyze the clinical efficacy of DAIR. The 122 patients were assigned into a cured group (81 cases) and an uncured group (41 cases). Risk factors were screened by univariate analysis out of their gender, age, body mass index, site of infection, type of infection (early postoperative infection or acute hematogenous infection), type of surgery (primary or revision), comorbidities, CRP, ESR, albumin and hemoglobin at admission, duration of symptoms, Staphylococcus aureus infection, multiple bacterial mixed infection, and preoperative sinus tract. For the factors of P<0.05, multivariate binary logistic regression analysis was used to determine the risk factors for failure of DAIR. Survival curves were plotted for the patients using DAIR failure as the endpoint event. Results:The CRP, ESR, VAS score, body temperature and white blood cell count at discharge in the 122 patients were significantly lower than the corresponding values at admission ( P<0.05). The success rate of DAIR was 66.39%(81/122). The multivariate binary logistic regression analysis suggested that duration of symptoms over 3 weeks( OR=1.230, 95% CI: 1.092~1.576, P=0.020), Staphylococcus aureus infection( OR=4.607, 95% CI: 2.057~10.318, P<0.001), preoperative sinus tract( OR=6.115, 95% CI: 2.630~14.220, P<0.001) and multiple bacterial mixed infection( OR=2.600, 95% CI: 1.131~5.977, P=0.020) were risk factors for DAIR failure; Kaplan-Meier survival curve also confirmed that the patients with Staphylococcus infection, multiple bacterial mixed infection, duration of symptoms over 3 weeks, or preoperative sinus tract had a significantly lower rate of survival than their controls ( P<0.05). Conclusions:For acute PJI, DAIR can be used to retain the prosthesis and control infection. However, DAIR is not recommended for the patients with Staphylococcus aureus infection, multiple bacterial mixed infection, symptoms lasting more than 3 weeks, or preoperative sinus formation.

Objective:To understand the etiology and clinical characteristics of hospitalized severe community-acquired pneumonia(SCAP) in Changchun, and provide scientific basis for its etiology diagnosis and targeted treatment.Methods:The study subjects included 618 children with clinical diagnosis of SCAP who were hospitalized from January 2016 to December 2019.We collected pharyngeal swabs and alveolar lavage fluid from children.Virus isolation, bacterial culture, time-of-flight mass spectrometry, PCR/RT-PCR, colloidal gold method and Optochin test were used to detect the antigen, nucleic acid and protein profiles in the specimen.Results:There were more boys than girls in hospitalized children with SCAP.The peak age of onset was 7 to 12 months.Most cases occurred in winter and spring.The highest detection rate of SCAP virus was 56.15%(347/618); 73.49%(255/347) were positive for one virus, among which the top five were respiratory syncytial virus (27.8%), influenza A virus (23.9%), influenza B virus (16.1%), rhinovirus (12.2%) and metapneumovirus (10.2%). Two viruses were positive for 19.88%(69/347); three viruses were positive for 4.32%(15/347); four viruses were positive for 2.31%(8/347). Atypical microbial infections were 29.77%(184/618), of which Mycoplasma pneumoniae accounted for 95.65%(176/184). Bacterial infections were 17.31%(107/618), mainly Streptococcus pneumoniae(39.25%, 42/107) and Staphylococcus aureus(24.30%, 26/107). The mixed infection of multiple pathogens was 7.61%(47/618), among which the mixed infection rates of Mycoplasma pneumonia with Streptococcus pneumoniae, virus were 40.43% and 34.04%, respectively.High fever, faster breathing, and perioral cyanosis were risk factors for SCAP, with OR and 95% CI of 7.71 and 4.56-13.04, 2.43 and 2.02-2.93, 3.53 and 2.56-4.86, respectively.Viral co-infection occurred in 36.96%(34/92) of complications such as heart failure, toxic encephalopathy, and myocardial damage; Mycoplasma pneumoniae and other pathogens co-infected 35.29% of children with pleural effusion. Conclusion:The pathogens of SCAP in Changchun are mainly viruses notably, respiratory syncytial virus is the dominant pathogen, followed by Mycoplasma pneumoniae.The bacterial pathogen is mainly Streptococcus pneumoniae.High fever, faster breathing, and cyanosis around the mouth are risk factors for severe pneumonia.Multi-pathogen mixed infection is prone to serious complications.

ERK pathway regulated the programmed death ligand-1 (PD-L1) expression which was linked to the response of programmed death-1 (PD-1)/PD-L1 blockade therapy. So it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer immunotherapy. In this study, PD0325901, an oral potent ERK inhibitor, strongly enhanced the efficacy of PD-1 antibody

Overexpression of adenosine triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG2) in cancer cells is known to cause multidrug resistance (MDR), which severely limits the clinical efficacy of chemotherapy. Currently, there is no FDA-approved MDR modulator for clinical use. In this study, rociletinib (CO-1686), a mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), was found to significantly improve the efficacy of ABCG2 substrate chemotherapeutic agents in the transporter-overexpressing cancer cells and in MDR tumor xenografts in nude mice, without incurring additional toxicity. Mechanistic studies revealed that in ABCG2-overexpressing cancer cells, rociletinib inhibited ABCG2-mediated drug efflux and increased intracellular accumulation of ABCG2 probe substrates. Moreover, rociletinib, inhibited the ATPase activity, and competed with [I] iodoarylazidoprazosin (IAAP) photolabeling of ABCG2. However, ABCG2 expression at mRNA and protein levels was not altered in the ABCG2-overexpressing cells after treatment with rociletinib. In addition, rociletinib did not inhibit EGFR downstream signaling and phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Our results collectively showed that rociletinib reversed ABCG2-mediated MDR by inhibiting ABCG2 efflux function, thus increasing the cellular accumulation of the transporter substrate anticancer drugs. The findings advocated the combination use of rociletinib and other chemotherapeutic drugs in cancer patients with ABCG2-overexpressing MDR tumors.

Objective To explore the management of spontaneous intraspinal hematoma.Methods From January 2011 to July 2018,29 cases with spontaneous intraspinal hematoma were admitted to our department.Date on etiology,clinical presentation,radiological features,treatment strategy and prognosis were analyzed retrospectively.The prognosis was assessed by American Spinal Injury Association impairment scale (ASIA) before and after the treatment.Results Total of 29 cases,only 10 cases (34.5％) revealed specific etiology,including 7 cases of spinal vascular malformation,2 of tumor apoplexy,1 of cavernous hemangioma.After 2 weeks of conservative treatment,3 patients with grade D and 3 patients with grade E were assessed for spinal function.The average interval from onset to surgery was(9.4±7.5) days,the ASIA after two weeks of the operation was as follows:5 patients were assessed at grade A,5 patients at grade C,8 patients at grade D and 4 patients at grade E.28 patients were followed up for (48.7±23.1) months on average,6 patients without surgery were E,22 cases with surgery were as follows:4 cases A,18 cases D/E.Conclusions The etiology of spontaneous intraspinal hematoma is hard to define even after complete preoperative examination and exploratory operation.The preoperative neurologic functions are important predicting factors for the prognosis of spontaneous intraspinal hematoma.For patients who had neurologic function deficit,surgical treatment should be performed urgently to remove the hematoma and release the decompression of spinal cord.The majority of these patients can achieve a positive prognosis after surgery.

Secalonic acid D (SAD) could inhibit cell growth in not only sensitive cells but also multidrug resistant (MDR) cells. However, the molecular mechanisms need to be elucidated. Here, we identified that SAD possessed potent cytotoxicity in 3 pairs of MDR and their parental sensitive cells including S1-MI-80 and S1, H460/MX20 and H460, MCF-7/ADR and MCF-7 cells. Furthermore, SAD induced cell G2/M phase arrest the downregulation of cyclin B1 and the increase of CDC2 phosphorylation. Importantly, JNK pathway upregulated the expression of c-Jun in protein level and increased c-Jun phosphorylation induced by SAD, which was linked to cell apoptosis c-Jun/Src/STAT3 pathway. To investigate the mechanisms of upregulation of c-Jun protein by SAD, the mRNA expression level and degradation of c-Jun were examined. We found that SAD did not alter the mRNA level of c-Jun but inhibited its proteasome-dependent degradation. Taken together, these results implicate that SAD induces cancer cell death through c-Jun/Src/STAT3 signaling axis by inhibiting the proteasome-dependent degradation of c-Jun in both sensitive cells and ATP-binding cassette transporter sub-family G member 2 (ABCG2)-mediated MDR cells.