Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Drug nanocrystals self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. There are more and more researches on DNSPE in the field of drug delivery in recent years. On the basis of summarizing the research status of DNSPE used as drug delivery systems, this paper comprehensively reviewed the research progress of three key issues, such as the main factors affecting construction of DNSPE, characterization methods of properties and structures, and in vivo fate, and looked forward to the industrialization prospect, which is beneficial to deepen the comprehensive research of DNSPE and promote its application in the field of drug delivery.

Objective:To investigate the effects of oral probiotics on intestinal microbiota and cognitive dysfunction in breast cancer chemotherapy patients. Methods:Thirty breast cancer patients who received anthracycline chemotherapy between December 2021 and June 2022 in the Department of Oncology, the First Affiliated Hospital of Bengbu Medical University were included in this study. The patients were randomly divided into the observation and control groups (15 cases per group). During chemotherapy, the observation group was additionally given oral probiotics. The fecal microbiota compositions before and after chemotherapy were detected using 16S rDNA sequencing. The changes in patients' subjective and objective cognitive function levels were evaluated by Montreal Cognitive Assessment (MoCA) and Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog), respectively. Results:The microbiota diversity, as indicated by the Chao, Ace, Shannon and Simpson indices, showed no significant difference between two groups (P>0.05). As compared with the control group, the relative abundance of the genus Actinomyces in the feces was significantly higher than in the observation group (P<0.05). By contrast, the relative abundance of the genera Acetoanaerobium, Lachnospiracea_incertae_sedis, and unclassified_Frankineae bacteria was significantly lower in the observation group (P<0.05). The total scores of the objective and subjective cognitive function as well as the scores of each dimension in both groups were markedly decreased after chemotherapy (P<0.05). The scores in the observation group were higher than those in the control group after chemotherapy (P<0.05). During chemotherapy, the presence of the gastrointestinal adverse reactions (constipation, nausea and vomiting, diarrhea and abdominal distension) in the observation group were significantly lower than in control group (P<0.05). Conclusion:Oral probiotics could improve the cognitive impairment and reduce the presence of the gastrointestinal side effects in the breast cancer patients receiving chemotherapy, which may be caused by modulating the intestinal microbiota.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Humans ; Otosclerosis/surgery* ; Stapes ; Stapes Surgery/adverse effects* ; Arteries

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

Humans ; Phosphorylation ; Serine ; Protein Serine-Threonine Kinases/metabolism* ; Spasms, Infantile

Facial paralysis causes both physical pain and psychological distress to patients. It is difficult for a patient with facial paralysis to engage with a normal social life and at work. Progresses have been made in recent years in the treatment of facial paralysis. More attentions have been caught by masseteric to facial nerve transposition, which has advantages of adjacency in location, abundancy in nerve supply and reliability in the outcome and now has deemed an important option of facial reanimation. It has not been long since the application of the technique of masseteric to facial nerve transposition in China, therefore it still lacks a universal guidance on practice. In order to achieve the aim of better quality control and popularisation of the technique, hereby a consensus with suggestions on facial reanimation with masseteric to facial nerve transposition is proposed as the reference for surgeons specialised in facial reanimation. This consensus is proposed, discussed and drafted by experts from plastic and reconstructive surgery, oral and maxillofacial surgery, head and neck surgery and neurosurgery.

Objective:To explore the association between atypical small acinar proliferation(ASAP)and subsequent diagnosis of intermediate and high risk prostate cancer(PCa),and analyze whether delaying repeat biopsy timing is safe and effective.Meth-ods:From June 2000 to June 2022,we retrospectively analyzed the clinical data of 276 patients accepting prostatic biopsy and diag-nosed with ASAP in China-Japan Union Hospital of Jilin University.54.7％(151/276)patients had a repeat biopsy.We used statis-tic methods to process the data.Results:25.2％(38/151)patients were diagnosed with PCa on repeat biopsy.Among them,78.9％(30/38)patients had Gleason score(GS)3+3 and 21.1％(8/38)had GS 3+4 disease.There were 4 and 6 patients got RP re-spectively in the two cohorts.Only 5.3％(8/151)of ASAP patients were diagnosed as intermediate risk PCa in repeated biopsy and specially,no high risk PCa was identified in our study.Conclusion:It was safe and valid to delay the repeat biopsy.

Objective: To investigate the experience of patients in the implementation of enhanced recovery after surgery (ERAS) strategy after radical gastrectomy and the factors affecting the treatment experience. Methods: A prospective cohort study was carried out. Patients who were diagnosed with gastric cancer by pathology and underwent radical gastrectomy at the Xijing Digestive Disease Hospital from December 2019 to December 2020 were consecutively enrolled. Those who received emergency surgery, residual gastric cancer surgery, preoperative neoadjuvant chemotherapy, non-curative tumor resection, intraperitoneal metastasis, or other malignant tumors were excluded. Patients' expectation and experience during implementation were investigated by questionnaires. The questionnaire included three main parts: patients' expectation for ERAS, patients' experience during the ERAS implementation, and patients' outcomes within 30 days after discharge. The items on the expectation and experience were ranked from 0 to 10 by patients, which indicated to be unsatisfied/unimportant and satisfied/important respectively. According to their attitudes towards the ERAS strategy, patients were divided into the support group and the reject group. Patients' expectation and experience of hospital stay, and the clinical outcomes within 30 days after discharge were compared between the two groups. Categorical data were reported as number with percentage and the quantitative data were reported as mean with standard deviation, or where appropriate, as the median with interquartile range (Q₁, Q₃). Categorical data were compared using the Chi-squared test or Fisher's exact test, where appropriate. For continuous data, Student's t test or Mann-Whitney U test were used. Complication was classified according to Clavien-Dindo classification. Results: Of the included 112 patients (88 males and 24 females), aged (57.8±10.0) years, 35 patients (31.3%) were in the support group and 77 (68.7%) in the reject group. Anxiety was detected in 56.2% (63/112) of the patients with score >8. The admission education during the ERAS implementation improved the patients' cognitions of the ERAS strategy [M(Q₁, Q₃) score: 8 (4, 10) vs. 2 (0, 5), Z=-7.130, P<0.001]. The expected hospital stay of patients was longer than the actual stay [7 (7, 10) days vs. 6 (6, 7) days, Z=-4.800, P<0.001]. During the ERAS implementation, patients had low score in early mobilization [3 (1, 6)] and early oral intake [5 (2.25, 8)]. Fifty-eight (51.8%) patients planned the ERAS implementation at home after discharge, while 32.1% (36/112) preferred to stay in hospital until they felt totally recovered. Compared with the reject group, the support group had shorter expected hospital stay [7 (6, 10) days vs. 10 (7, 15) days, Z=-2.607, P=0.009], and higher expected recovery-efficiency score [9 (8, 10) vs. 7(5, 9), Z=-3.078, P=0.002], lower expected less-pain score [8 (6, 10) vs. 6 (5, 9) days, Z=-1.996, P=0.046], expected faster recovery of physical strength score [8 (6, 10) vs. 6 (4, 9), Z=-2.200, P=0.028] and expected less drainage tube score [8 (8, 10) vs. 8 (5, 10), Z=-2.075, P=0.038]. Worrying about complications (49.1%) and self-recognition of not recovery (46.4%) were the major concerns when assessing the experience toward ERAS. During the follow-up, 105 patients received follow-up calls. There were 57.1% (60/105) of patients who experienced a variety of discomforts after discharge, including pain (28.6%), bloating (20.0%), nausea (12.4%), fatigue (7.6%), and fever (2.9%). Within 30 days after discharge, 6.7% (7/105) of patients developed Clavien-Dindo level I and II operation-associated complications, including poor wound healing, intestinal obstruction, intraperitoneal bleeding, and wound infection, all of which were cured by conservative treatment. There were no complications of level III or above in the whole group after surgery. Compared with the support group, more patients in the reject group reported that they had not yet achieved self-expected recovery when discharged [57.1% (44/77) vs. 22.9% (8/35), χ²=11.372, P<0.001], and expected to return to their daily lives [39.0% (30/77) vs. 8.6% (3/35), χ²=10.693, P<0.001], with statistically significant differences (all P<0.05). Only 52.4% (55/105) of patients returned home to continue rehabilitation, and the remaining patients chose to go to other hospitals to continue their hospitalization after discharge, with a median length of stay of 7 (7, 9) days. Compared with the reject group, the support group had a higher proportion of home rehabilitation [59.7% (12/33) vs. 36.4% (43/72), χ²=4.950, P=0.026], and shorter time of self-perceived postoperative full recovery [14 (10, 20) days vs. 15 (14, 20) days, Z=2.100, P=0.036], with statistically significant differences (all P<0.05). Conclusions: Although ERAS has promoted postoperative rehabilitation while ensuring surgical safety, it has not been unanimously recognized by patients. Adequate rehabilitation education, good analgesia, good physical recovery, and early removal of drainage tubes may improve the patient's experience of ERAS.
Enhanced Recovery After Surgery ; Female ; Gastrectomy ; Humans ; Length of Stay ; Male ; Pain ; Patient Outcome Assessment ; Postoperative Complications/surgery* ; Prospective Studies ; Retrospective Studies ; Stomach Neoplasms/surgery* ; Treatment Outcome