Objective:To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR.Methods:A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m 2 day 1, cisplatin 25 mg/m 2 days 1-3, and capecitabine 800 mg/m 2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results:A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm 3. The T stage ( OR=12.71, 95% CI: 1.4-112.5, P=0.022) and the volume ( OR=7.1, 95% CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion:The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Objective To explore the potential categories of self-regulatory fatigue among maintenance hemodialysis patients and their relationships with self-management. Methods A total of 502 maintenance hemodialysis patients in Lanzhou were surveyed using a general information questionnaire, a Self-Regulatory Fatigue Scale, and a Self-Management Scale for Hemodialysis Patients. Potential profile analysis was conducted on self-regulatory fatigue, and its relationship with self-management was explored. Results Based on their self-regulatory fatigue status, maintenance hemodialysis patients could be categorized into four potential groups: low self-regulatory fatigue group (5.0%), moderate self-regulatory fatigue group (49.2%), high self-regulatory fatigue group (13.9%), and high cognitive regulatory fatiguegroup (31.9%). Gender, education level, and monthly per capita family income were identified as influencing factors for the potential categories of self-regulatory fatigue. Significant differences were observed in the total self-management scores among patients belonging to different potential categories of self-regulatory fatigue (F=50.617, P < 0.001). Conclusion Maintenance hemodialysis patients can be classified into four potential categories of self-regulatory fatigue, with patients in the low self-regulatory fatigue group demonstrating higher levels of self-management. Reducing the level of self-regulatory fatigue can contribute to enhancing patients'self-management capabilities.

OBJECTIVE To investigate the antibacterial activities of flavaspidic acid BB against the main pathogens of skin and soft tissue infections such as methicillin -resistant Staphylococcus aureus （MRSA）and methicillin -sensitive Staphylococcus aureus （MSSA） in vitro and in vivo . METHODS Microdilution method was used to determine the minimum inhibitory concentration（MIC）and minimum bactericidal concentration （MBC）of flavaspidic acid BB on 10 strains of MRSA and 13 strains of MSSA ；time-kill curves of MRSA 11 and MSSA 23 strains were drawn by plate method ；the checkerboard dilution method was used to determine the combined antibacterial effect of flavaspidic acid BB and mupirocin ；the skin abscess model of mice was established to evaluate the antibacterial effects of 0.5%，1%，2% flavaspidic acid BB cream on MRSA 11 or MSSA 23 strains in vivo；scanning electron microscopy was used to observe the effects of flavaspidic acid BB on the morphology of MRSA 11 or MSSA23 strains. The contents of nucleic acid leakage and extracellular protein were also determined . RESULTS MIC and MBC ranges of flavaspidic acid BB against 10 strains of MRSA were 6.30-80.00 μg/mL and 40.00-640.00 μg/mL；MIC and MBC ranges of 13 strains of MSSA were 40.00-80.00 μg/mL and 63.50-126.99 μg/mL，respectively. The bactericidal rate of MRSA 11 and MSSA23 strains were 99.9% after interfered with plavaspidic acid BB for 36 h. The combination of flavaspidic acid BB and mupirocin showed an additive effect on MRSA strain and an additive or synergistic effect on MSSA strain . The 0.5%，1% and 2% flavaspidic acid BB cream could reduce the volume of abscess and the bacterial load of skin abscess model mice to some extent （P＜0.05），and improved the pathological changes of skin inflammation in skin abscess site of mice . Flavaspidic acid BB could make MRSA 11 and MSSA 23 cells shrinkage and rupture ，and significantly increase the contents of nucleic acid leakage and extracellular protein （P＜0.01）. CONCLUSIONS Flavaspidicacid BB shows good antibacterial effect on MRSA and MSSAE-mail：tchp66@163.com in vitro and in vivo ，the mechanism of which may be related to the change of membrane permeability .

OBJECTIVE To study the effects of yunaconitine on myocardial injury in rats and its mechanism related to mitochondrial apoptosis pathway rats. METHODS Forty SD rats were divided into normal group （normal saline）， yunaconitine high-dose and low-dose groups（0.14， 0.09 mg/kg）and aconitine group （positive control， 0.88 mg/kg） by random number method， with 10 rats in each group. They were given relevant medicine intragastrically， once a day， for consecutive 7 days. The levels of lactate dehydrogenase （LDH）， creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， superoxide dismutase （SOD） and malondialdehyde （MDA） in serum as well as the level of reactive oxygen species （ROS） in myocardial tissue were detected. The pathomorphological changes of myocardium and ultrastructural changes of myocardial mitochondria were all observed. The apoptosis of cardiomyocytes was determined. The protein relative expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 were determined in myocardium of rats. RESULTS Compared with normal group， the serum levels of LDH， CK， CK-MB and MDA， the apoptotic numbers of cardiomyocytes， the level of ROS and protein expression of caspase-3 in myocardium were increased significantly in yunaconitine high-dose and low- dose groups （P＜0.05 or P＜0.01）； serum level of SOD and Bcl-2/Bax ratio in myocardium were all decreased significantly （P＜ 0.01）； the protein relative expressions of caspase-9， cleaved-caspase-9， caspase-3 and cleaved-caspase-3 in myocardium were significantly increased in yunaconitine high-dose group （P＜0.05）； some pathomorphological changes were found in 2 groups， such as myocardial fiber disorder， mitochondrial swelling. CONCLUSIONS Yunacotine could cause myocardial injury in rats. Its mechanism might be related to destroying the integrity of cardiomyocyte membrane， causing oxidative stress of cardiomyocyte， and inducing the apoptosis of myocardial cells through mitochondrial pathway.

OBJECTIVE：To study the effect of isofla vaspidicacid PB （called PB for short ）on the biofilm adhesion and the gene expression of ergosterol metabolism related enzymes in Trichophyton rubrum . METHODS ：M38-A2 method was adopted to determine MIC of PB to T. rubrum . MTT assay was used to screen the biolfilm condition and initial adhesion period of T. rubrum . The effects of different concentrations of PB （40，80，160 µg/mL）on the adhesion duration of T. rubrum （growth control group without PB was set up ，similarly hereinafter ）were evaluated and the adhesion rate was calculated by using XTT assay ；the effects of different concentrations of PB （20，40，80 µg/mL）on the biofilm formation of T. rubrum at different initial adhesion periods （3，5，9 h）were observed and the adhesion rate was calculated by using XTT assay combined with inverted microscope ；qRT-PCR method was used to detect the effects of PB （320 µg/mL）on the mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11 in biofilm of T. rubrum . RESULTS ：MIC of PB to T. rubrum was 20 µg/mL. The biofilm of T. rubrum in RPMI-1640 medium containing 10％ FBS was the most metabolism activity at 6 h of initial adhesion. Compared with growth control group ，after treated with different concentrations of PB ，adhesion rate and mRNA expression of ERG6 and ERG11 in biofilm were decreased significantly （P＜0.01）. Hyphae decreased or even disappeared ，and the adhesion inhibition rate （at 5 and 9 h of initial adhesion ）increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS ：PB can inhibit the adhesion of T. rubrum and reduce the hyphae ；the mechanism may be associated with the inhibition of the biofilm adhesion and mRNA expression of ergosterol metabolism related enzyme gene ERG6 and ERG11.

OBJECTIVE：To study the toxicity mechanism of yunacotine-induced arrhythmia in rats. METHODS ：Totally 32 rats were randomly divided by random number table method into normal control group ，yunacotine low-dose and high-dose groups （0.09，0.14 mg/kg），aconitine group （positive control ，0.88 mg/kg），with 8 rats in each group. Administration groups were given the corresponding drugs once a day ，and normal control group was given the constant volume of normal saline ，for consecutive 7 d. After last intragastric administration ，the changes of electrocardiogram （ECG） were observed. The contents of adenosine triphosphate（ATP）in myocardial tissue and Ca 2+ in myocardial cells ，the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase as well as the protein expression of ranolidine receptor 2（RyR2）and Ca 2+-ATPase（SERCA2）in myocardial tissue were determined. RESULTS：Compared with normal control group ，time limit of QRS wave and QTc intervals of rats were prolonged significantly in yunaconitine low-dose group （P＜0.01）. The content of Ca 2 + in myocardial cells ， the ATP contents ， the activities of Ca2+-Mg2+-ATPase and Na +-K+-ATPase as well as the protein expression of SERCA 2 in myocardial tissue were reduced significantly （P＜0.05 or P＜0.01）. The heart rate of rats in yunaconitine high-dose group and aconitine group were increased significantly （P＜ 0.05 or P＜0.01），and time limit of QRS wave and QTc intervals were significantly prolonged （P＜0.01）；the content of Ca 2+ in myocardial cells was increased significantly （P＜0.01）；ATP content ，the activities of Ca 2+-Mg2+-ATPase and Na +-K+-ATPase，and protein expression of RyR 2 and SERCA 2 in myocardial tissue were decreased significantly （P＜0.01）. CONCLUSIONS ： Yunaconitine can induce arrhythmia in rats ，the mechanism of which may be associated with Ca 2+ overload that resulted from reducing the activities of Na +-K+-ATPase and Ca 2+-Mg2+-ATPase and down-regulating the expression of related calcium transporter RyR2 and SERCA 2.

Objective To compare vein valve function following pharmacomechanical thrombolysis (PMT) with simple catheter-directed thrombolysis (CDT) for deep vein thrombosis. Methods We retrospectively analyzed the clinical data of sixty patients who suffered acute lower extremity deep vein thrombsis in our hospital between October 2016 and March 2017. All patients underwent contralateral preprocedural duplex and bilateral postprocedure duplex to access patency and valve function. The patients were divided into three groups including a group A with catheter-directed thrombolysis (CDT) alone (36 patients with 20 males and 16 females at average age of 56 years), a group B with PMT alone (15 patients with 8 males and 7 females at average age of 55 years), and a group C with PMT combined CDT (9 patients with 4 males and 5 females at average age of 56 years). The valve function was compared among the Group A, Group B and Group C. Results There were 40.0% (24/60) patients with bilateral femoral vein valve reflux, 40.0% (24/60) patients with unilateral femoral vein valve reflux (all in the treated limbs), 20% (12/60) patients had no reflux in both limbs. Of the limbs treated with CDT alone, PMT alone and PMT combined CDT, the rate of valve reflux was 38.9% (14/36), 33.3% (5/15), and 55.6% (5/9) respectively (P=0.077). Conclusion In the patients suffering acute DVT, PMT or PMT combined CDT does not hamper valve function compared with CDT alone.

Objective: To analyze genomic features of pathogens based on next generation sequencing technique in a food-borne disease event. Methods: A total of 11 blood samples, stomach contents before gastric lavage from the death and patients' foods were collected. S. aureus, B. cereus and toxic substances were detected. B. cereus detected in foods were counted. The conserved region of 16 S rDNA gene and ces gene(cereulide) of B. cereus isolates were detected by real-time PCR. Next Generation Sequencing (NGS) technology was applied to acquire genome sequences of isolates. Different plasmids distribution and comparative genomics analysis with reference sequences in public databases were analyzed. Results: Only B. cereus tested positive in all samples. The counts of B. cereus in Egg fried rice, one food samples, were 1.9×10⁷ CFU/g, and the counts of B. cereus in dried and fried fish and brine pork head meat samples were 3.0×10³ CFU/g both. Ten isolates were carrying hlyⅢ, nheA, nheB, inlA and inhA genes, and nine isolates carried the plcR gene and nine isolates carried the nheC gene. The PCR result of 16 S rDNA gene and ces gene of all isolates were positive. All carried the complete ces genes cluster sequence which were identical to the sequence of plasmid pCER270 (NC_01 0924.1) from strain AH187 in United Kingdom and pNCcld (NC_016792.1) from NC7401 in Japan. The alignment of plasmids turned out the sequence of the isolate differed from the pXO1 and pXO2 plasmids of B. anthracis, but carried the pNCcld plasmid containing the ces genes cluster. The phylogenetic tree based on genomic sequences of ten isolates showed high similarity (distances in phylogenetic tree from 2.0×10^-6-9.0×10^-6) to each other and to the B. cereus strains AH187 and NC7401 (MLST ST26 type, distances in phylogenetic tree from 3.8×10^-5-4.5×10^-5). Conclusion The foodborne disease event was caused by vomiting type Bacillus cereus without plasmid pXO1 and pXO2 contaminated egg fried rice. The vomiting-type food poisoning caused by B. Cereus globally is probably associated with ST26, ST164 and other strains harboring ces gene.

Objective To investigate the effects of four interior-warming drugs( galangal,cinnamon,evodia rutaecarpa,and dried ginger)on the tension of ileum smooth muscle and Ca2+-ATPase on the cell membrane in rabbits. Methods The effects of galangal,cinnamon,evodia rutaecarpa,and dried ginger were examined on normal ileum smooth muscle,in vitro intestinal muscle contraction caused by acetylcholine(ACh),barium chloride(BaCl2 )and histamine(His), and ACh-induced calcium release by using BL-420E+ biological signal collection and processing system.The average tension was measured within 1 min before delivery and within 3 minutes after the treatment,and the inhibition rate was calculated according to the average tension value.The effects of sera containing galangal,cinnamon,evodia rutaecarpa,and dried ginger on Ca2+-ATPase activity on the cell membrane of the intestinal smooth muscle were examined by phosphorus method. Results Galangal,cinnamon,evodia rutaecarpa,and dried ginger at high concentrations could restrain in vitro intestinal contraction in normal circumstances(P<0.05 or P<0.01).Significant inhibitory effects on intestinal contraction caused by ACh,His and BaCl2 were found in low,medium and high concentration groups(P<0.01).There was a dose-effectiveness relationship between the inhibition rate and final drug concentrations.The ACh-induced intracellular and extracellular calcium dependent contraction were significantly inhibited by the four interior-warming drugs( P < 0. 05 or P < 0. 01). The Ca2+-ATPase activities were( 0. 384 ± 0.070),(0.302±0.016),(0.307±0.016),(0.296±0.016),(0.313±0.003)U·mg-1 ,respectively,in intestinal smooth muscle in normal control group and high concentration groups of galangal,cinnamon,evodia rutaecarpa,and dried ginger(P<0.01). Conclusion Interior-warming drugs may relax intestinal smooth muscle by reducing the intracellular calcium release and the extracellular calcium inflow via receptor-controlled calcium channels,and inhibiting the Ca2+-ATPase activity in smooth muscle.

Objeetive:To screen the different extracts from Geranium strictipes with anticaries activity,and to study the effect of the active extract on the production of acid and polysaccharides of oral cariogenic bacteria.Methods:Chlorhexidine and Galla Chinensis were used as the positive controls.Tube double dilution method was used to study the extracts of Geranium strictipes on the growth of Streptococcus mutans (S.mutans) and Actinomyce viscosus (A.viscosus).First,the activity of 5 extracts fom Geranium strictipes against S.mutans,A.viscosus was detected.Their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were obtained.The effects of 4 lower concentrations(＜ MIC) of the active extract on the production of oral bacterial acid polysaccharides were examined.Results:The effect of n-butanol extraction part of Geranium strictipes was the strongest among all the extracts against the two kinds of bacteria in the inhibition of bacteria growth,bacterial acid production and polysaccharides production,but weaker than that of Chlorhexidine and Galla Chinensis.Conclusion:N-butanol extraction part of Geranium strictipes may be a natural and effective anti-caries agent.