Objective: To investigate whether zerumbone ( ZER) has the effect of preventing cisplatin ( Cis) -induced acute kidney injury (Cis-AKI) . Methods: The MTT method was used to detect the effect of different concentrations of ZER on the cell viability of Cis-AKI. The in vivo and in vitro models of Cis-AKI mice were estab- lished by dividing into control group , separate administration group , model group , and dose group. Western blot and immunofluorescence experiments were used to detect the expression changes of kidney injury marker-1 ( KIM- 1) , phosphorylated NF-κB p65 ( P-p65 ) , Cleaved casepase3 , receptor interacting protein kinase 1 ( RIPK1) , RIPK3 , and tumor necrosis factor-α (TNF-α) . Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of KIM-1 , TNF-α , interleukin-6 ( IL-6) , and monocyte chemoattractant protein-1(MCP-1) . Periodic acid-Schiff (PAS) staining confirmed the therapeutic effect of ZER on Cis-AKI. RNA-seq and cell thermal shift (CETSA) were used to explore possible target proteins. Results : MTT results showed that ZER could alleviate the decrease in cell viability of Cis-AKI ; in vivo and in vitro studies showed that compared with the model group , after treatment with ZER , its KIM-1 , P-p65 , Cleaved casepased3 , RIPK1 , RIPK3 , TNF -α expres- sion decreased significantly , and the mRNA expression of KIM-1 , TNF-α , IL-6 mRNA , and MCP-1 decreased. PAS staining showed that ZER had a therapeutic effect on Cis-AKI. RNA-seq and CETSA analysis showed that ZER might prevent and treat Cis-AKI by targeting the PIM1 protein. Conclusion ZER may alleviate Cis-AKI and im- prove inflammatory response and necroptosis by regulating PIM1 protein. ZER is expected to be a potential drug for the prevention and treatment of Cis-AKI.

Objective To observe the clinical efficacy and safety of external application of Piyan Formula in treating epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs)-related rashes.Methods Sixty cases of EGFR-TKIs-related rash patients were randomly allocated into either a treatment group or a control group.The treatment group received external application of Piyan Formula to the rash area twice daily for 14 days.The control group received external application of fucidic acid cream to the rash area twice daily for 14 days.Changes in rash grading,itching grading,quality of life scores and adverse event were observed and recorded in both groups.At the same time,levels of hypersensitive C-reactive protein,interleukin(IL)-6,and IL-1β were measured before treatment and 24 hours after treatment.Results After treatment,the rash severity,itching severity,and quality of life scores were notably lower in the treatment group compared to the control group(P<0.05).The levels of hypersensitive C-reactive protein,IL-6,and IL-1β exhibited a significant decrease compared to their pre-treatment values.(P<0.05).Compared with the control group,the levels of hypersensitive C-reactive protein,IL-6,and IL-1β decreased in the treatment group,with statistically significant differences(P<0.05).No adverse events related to Piyan Formula or fucidic acid cream occurred during the treatment process.Conclusion External application of Piyan Formula in treating EGFR-TKIs-related rashes shows significant clinical efficacy,can effectively reduce the levels of inflammatory factors,and has high safety,thus warranting clinical promotion.

Objective To investigate the effects of perioperative goal-directed fluid therapy (GDFT) on hemodynamics, postoperative recovery, and complications in elderly patientswith gastric cancer radical surgery complicated by hypertension. Methods A total of 88 elderly patients with gastric cancer radical surgery complicated by hypertension were enrolled and randomly divided into treatment group and control group, with 44 patients in each group. The treatment group received GDFT during the perioperative period, while the control group received conventional fluid therapy. The mean arterial pressure, heart rate, and central venous oxygen saturation (ScvO₂) at different time points, as well as postoperative exhaust time, postoperative hospital stay, and postoperative complication rates were compared between the two groups. Results The time effects (F=60.488, 49.789, 39.423), intergroup effects (F=17.317, 12.969, 10.101), and interaction effects (F=26.415, 22.546, 17.294) of mean arterial pressure, heart rate, and ScvO₂ in the two groups showed statistically significant difference(P < 0.05). After surgery, the mean arterial pressure, heart rate, and ScvO₂ in the treatment group were higher than those before anesthesia and the control group (P < 0.05). The postoperative exhaust time and hospital stay in the treatment group were (2.25±0.61) and (10.29±1.96) days, respectively, which were shorter than (2.82±0.71) and (12.36±2.29) days in the control group (P < 0.05). The total incidence of postoperative complications in the treatment group was lower than that in the control group (11.36% versus 29.54%, P < 0.05). Conclusion Applying GDFT during the perioperative period for elderly patients with gastric cancer radical surgery complicated by hypertension can provide a more stable hemodynamic environment, improve tissue perfusion, accelerate postoperative recovery, and reduce postoperative complications.

OBJECTIVE To systematically review the background of bioequivalence assessment of nasal sprays and nasal aerosols and the guiding considerations for the bioequivalence assessment of these complex drug-device combination products by regulatory authorities in the United States, the European Union(EU) and China. METHODS This article provided detailed explanations on the innovative weight of evidence assessment approach adopted by the US Food and Drug Administration(FDA), and the statistical rationale, methods and considerations for the bioequivalence assessment of nasal sprays and nasal aerosols. Using the calculation methods described in the draft guidance for budesonide inhalation suspension and the draft guidance for fluticasone nasal spray propionate issued by FDA, the statistical parameters of two-sided and one-sided population bioequivalence calculation were realized through R language programming, and pseudo-code for the population bioequivalence (PBE) calculation programs was provided. This article also presented a comprehensive review of published guidelines and summaries review principles of the EU and China for nasal sprays and nasal aerosols equivalence assessment. RESULTS & CONCLUSION Nasal sprays/nasal aerosols is the focus of innovative and generic drug development in recent years. This paper provided valuable considerations references for the research and development, quality control and bioequivalence evaluation of generic preparations of nasal sprays/nasal aerosols.

Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S reaction refers to the condensation and recyclization of β-arylethylamine with aldehyde or ketone under acidic conditions to form tetrahydroisoquinoline and β-carboline alkaloid derivatives. The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development.
Alkaloids/chemistry* ; Catalysis ; Enzymes/metabolism* ; Research/trends* ; Tetrahydroisoquinolines/chemistry*

Objective To analyze dialectical thinking and medication laws of TCM master LI Ji-ren in treating rheumatoid arthritis (RA); To provide references for clinical medication. Methods Medical cases of RA in outpatient department of the First Affiliated Hospital of Wannan Medical College during January 2014 to June 2015 treated by Professor LI Ji-ren. SPSS18.0 statistical software was used to carry out frequency analysis, correlation analysis, and cluster analysis. Results The included medical cases covered 123 cases, 199 prescriptions and 211 kinds of medicine. The total medication frequency was 3503, with 52 kinds of high frequency medicine (>10%), including Astragali Radix, Angelicae Sinensis Radix, Scorpio, Spatholobi Caulix, and Sargentodoxae Caulix. 36 kinds of medicine belonged to Liver Meridian of Foot-Jueyin (69.2%); 21 kinds of medicine belonged to Kidney Meridian of Foot-Shaoyin (40.4%); 20 kinds of medicine belonged to Spleen Meridian of Foot-Taiyin (38.5%); 16 kinds of medicine belonged to Heart Meridian of Hand-Shaoyin (30.8%). High frequency medicine was mainly to be sweet, spicy and bitter. High frequency medicine was mainly to be medicine with the functions of clearing heat, tonifying (tinifying qi, blood, yang and yin), activating blood and expelling stasis, and expelling rheumatism. 127 pairs of high frequency medicine was in positive correlation, among which 36 pairs showed the correlation coefficient >0.9. High frequency cluster analysis could be mainly divided into 6 categories. Conclusion The medication laws in this study and Professor LI Ji-ren's treatment for RA emphasize consolidating basis, and are in accordance with the ideas of expelling wind and humidity, activating blood and expelling stasis and stopping pain, which can provide references for clinic.

Objective To sum up the experience of position nursing of patients with ankylosing spondylitis and severe kyphosis. Methods Eleven patients with ankylosing spondylitis and severe kyphosis underwent surgery. The patients′spine and head were kept in a line during anesthesia to avoid spinal cord injury. The eye mask was used to make sure the eyelid close, so the bulbar conjunctiva and corneal did become dry. The angle of operation bed in time during operation was adjusted. The crushed area was observed and the position was changed to avoid pressure sores and edema. After surgery, they were keep inactive to make sure the spine stable and relieve the pressure. Results The 11 patients′surgery were successful. There were no pressure ulcer, fracture, spinal cord injury or eye injury occurs. The operation time was 9.3 ± 2.9 h. Conclusion Position nursing is very important to improve the success rate of surgery and reduce complications.

ObjectiveTo observe the clinical efficacy ofTong Du Tiao Shen(unblocking the Governor Vessel and regulating spirit) needling method plus Nimodipine in treating vascular dementia.MethodSixty patients with vascular dementia were randomized into a treatment group and a control group, 30 in each group. The control group was intervened by oral administrationof Nimodipine, while the treatment group was additionally intervened byTong Du Tiao Shenneedling method. Two weeks were taken asa treatment course, and the intervention lasted 2 courses. The Mini-Mental State Examination (MMSE) and Activities of Daily Life (ADL) were evaluated and compared before and after intervention, and the therapeutic efficacy was determined.Result After intervention, there were significant differences in comparing MMSE and ADL scores between the two groups (P<0.05). ConclusionTong Du Tiao Shenneedling method plus Nimodipine is effective in treating vascular dementia, and worth promotion in clinic.

OBJECTIVETo evaluate the quality and clinical applicability of pyrosequencing assay kit for detecting hepatitis B virus resistance (HBV DRT).

METHODSSerial dilutions of the International Standard for HBV DNA were used to test the detection limit of the PCR for HBV DRT. Plasmids containing the either a wild-type (WT) copy or one of 10 mutant (MT) copies of the HBV RT gene were used to prepare a series of samples with various mutation ratios. To construct the linear relationship between the true mutation rate and the detected mutation rate, each sample was repeated at least 10 times. A total of 102 clinical samples were analyzed by Sanger sequencing and retested by the PCR for HBV DRT to determine the concordance of these two methods.

RESULTSThe lower detection limit of the PCR for HBV DRT was 50 IU/ml. Except for the RT236 MT, the correlation between the true mutation rate and the detected mutation rate for the other nine resistance-related mutation sites were excellent, with R² more than 0.98 (P less than 0.001). Among the 102 clinical samples, four were not amplified successfully by PCR. The results were significantly different between the PCR for HBV DRT method and the Sanger sequencing method (x² = 71.2, P less than 0.001), and concordance was observed for 897/969 (92.6%) amino acid positions in 98 samples. Concordant results were achieved in 46/98 (46.9%) samples at all 10 mutation sites. For detection of a single mutation site, concordance rates ranged from 71.5% to 100% at the 10 mutation sites, respectively. Analysis of discordant samples showed that in 87.5% (63/72), Sanger sequencing detected WT and the PCR for HBV DRT detected WT/MT. In 5.6% (4/72) of samples, Sanger sequencing detected WT/MT and the PCR for HBV DRT detected WT. In the remaining 6.9% (5/72) of samples, Sanger sequencing detected WT but PCR for HBV DRT detected MT.

CONCLUSIONThe PCR for HBV DRT showed high sensitivity and accuracy in detecting antiviral drug-resistant mutations. The method is superior to Sanger sequencing for detecting minor mutations and can be used for early detection of a resistance mutation.

Objective To evaluate the toxicity and efficacy of thermotherapy used with a streptococcus A preparation (OK-432) and cisplatin for treating malignant pleural effusion (MPE),and to assess patients' tolerance.Methods A total of 158 MPE patients were randomized into experimental and control groups.Closed drainage of the thoracic cavity was conducted with all the patients using a central venous catheter,and systematic chemotherapy was administered individually on the basis of each patient's condition.Patients in the control group were treated with intrapleural administration of OK-432 (0.5 mg) and cisplatin (40-60 mg) weekly for a maximum of 4 weeks,while those in the experimental group were given 60min of high frequency electrical thermotherapy 30-60 min after the administration of the drugs.The thermotherapy was at 40-43.5 ℃ and administered twice a week.Efficacy,quality of life and toxicity were compared between the two groups.Results The overall response rate in the experimental and control groups was 90.6% and 79.5% respectively;and grade I-II toxicity was similar.No grade Ⅲ or more serious toxicity was observed.The life quality scores in both groups were significantly improved after treatment.Conclusions Thermotherapy combined with intrapleural OK-432 and cisplatin can improve the effectiveness of therapy and life quality in MPE patients without increased toxicity.