Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

ObjectiveTo investigate the protective effect of the extract of Liuwei Dihuangwan （LW） on mitochondrial damage in the Alzheimer's disease （AD） model of Caenorhabditis elegans （C. elegans）. MethodC. elegans transfected with human β-amyloid protein （Aβ） _1-42 gene was used as an AD model. The rats were divided into blank group， model group， metformin group （50 mmol·L^-1）， and low， medium， and high dose （1.04， 2.08， 4.16 g·kg^-1） LW groups. Behavioral methods were used to observe the sensitivity of 5-hydroxytryptamine （5-HT） in nematodes. Western blot was used to detect the expression of Aβ in nematodes. Total ATP content in nematodes was detected by the adenine nucleoside triphosphate （ATP） kit， and mitochondrial membrane potential was detected by the JC-1 method. In addition， the mRNA expression of Aβ expression gene （Amy-1）， superoxide dismutase-1 （SOD-1）， mitochondrial transcription factor A homologous gene-5 （HMG-5）， mitochondrial power-associated protein 1 （DRP1）， and mitochondrial mitoprotein 1 （FIS1） was detected by real-time fluorescence quantitative polymerase chain reaction （RT-PCR）. ResultThe extract of LW could reduce the hypersensitivity of the AD model of nematodes to exogenous 5-HT （P<0.05） and delay the AD-like pathological characteristics of hypersensitivity to exogenous 5-HT caused by toxicity from overexpression of Aβ in neurons of the AD model of nematodes. Compared with the blank group， in the model group， the mRNA expression of Aβ protein and Amy-1 increased （P<0.01）， and the mRNA expression of SOD-1 and HMG-5 decreased （P<0.01）. The mRNA expression of DRP1 and FIS1 increased （P<0.01）， and the level of mitochondrial membrane potential decreased （P<0.05）. The content of ATP decreased （P<0.01）. Compared with the model group， in the positive medicine group and medium and high dose LW groups， the mRNA expression of Aβ protein and Amy-1 decreased （P<0.05，P<0.01）， and the mRNA expression of SOD-1 and HMG-5 increased （P<0.01）. The mRNA expression of DRP1 decreased （P<0.05，P<0.01）， and that of FIS1 decreased （P<0.01）. The level of mitochondrial membrane potential increased （P<0.01）， and the content of ATP increased （P<0.05，P<0.01）. ConclusionThe extract of LW may enhance the antioxidant ability of mitochondria， protect mitochondrial DNA， reduce the fragmentation of mitochondrial division， repair the damaged mitochondria， adjust the mitochondrial membrane potential， restore the level of neuronal ATP， and reduce the neuronal damage caused by Aβ deposition.

Objective:To investigate the protective effect of ulinastatin on sepsis-acute kidney injury (SA-AKI) by NF-κB signaling pathway.Methods:Total of 60 mice were randomly(random number) divided into sham group, cecal ligation puncture group (CLP group) and ulinastatin treatment group (CLP+UTI group). Ulinastatin treatment group was intraperitoneally injected with ulinastatin 50 000 U/kg once a day. 24 hours after operation, five mice were sacrificed, the kidney tissues were collected to observe renal histopathology by HE staining. The macrophage infiltration was observed by immunohistochemistry. The remaining mice in each group were used to calculate the survival rate of 7-day after operation. HK-2 cells were stimulated by LPS to obtain the SA-AKI model, and the cells were divided into control group, LPS group and LPS + UTI group. CCK-8 assay was used to detect cell viability, EdU assay was used to detect cell proliferation, and JC-1 assay was used to detect mitochondrial damage. The phosphorylation degree of NF-κB was detected by western blot. Inflammatory factors concentrations of cellular supernatant were detected by ELISA assay.Results:Compared with the sham group, the kidney tissue of mice in CLP group showed that kidney pathological obvious changed, the infiltration of macrophages increased, and the survival rate of mice decreased. CLP+ UTI group reduced the pathological changes and the infiltration of macrophages, improved the survival rate of mice. Compared with control group, LPS group obviously inhibited the cells activity and proliferation of HK-2 cells, damaged the mitochondrial membrane potential of HK-2 cells. Compared with LPS group, LPS+ UTI group attenuated the phosphorylation of NF-κB, decreased the secretion of inflammatory factors, rescued the activity and proliferation of HK-2 cells, and reduced the damage of HK-2 mitochondrial membrane potential.Conclusions:Ulinastatin can reduce mitochondrial damage, inhibit the secretion of inflammatory factors and improve the function of renal tubular epithelial cells through regulating NF-κB signaling pathway.

Objective:To evaluate artificial intelligence constructed by deep convolutional neural network (DCNN) for the site identification in upper gastrointestinal endoscopy.Methods:A total of 21 310 images of esophagogastroduodenoscopy from the Cancer Hospital of Chinese Academy of Medical Sciences from January 2019 to June 2021 were collected. A total of 19 191 images of them were used to construct site identification model, and the remaining 2 119 images were used for verification. The performance differences of two models constructed by DCCN in the identification of 30 sites of the upper digestive tract were compared. One model was the traditional ResNetV2 model constructed by Inception-ResNetV2 (ResNetV2), the other was a hybrid neural network RESENet model constructed by Inception-ResNetV2 and Squeeze-Excitation Networks (RESENet). The main indices were the accuracy, the sensitivity, the specificity, positive predictive value (PPV) and negative predictive value (NPV).Results:The accuracy, the sensitivity, the specificity, PPV and NPV of ResNetV2 model in the identification of 30 sites of the upper digestive tract were 94.62%-99.10%, 30.61%-100.00%, 96.07%-99.56%, 42.26%-86.44% and 97.13%-99.75%, respectively. The corresponding values of RESENet model were 98.08%-99.95%, 92.86%-100.00%, 98.51%-100.00%, 74.51%-100.00% and 98.85%-100.00%, respectively. The mean accuracy, mean sensitivity, mean specificity, mean PPV and mean NPV of ResNetV2 model were 97.60%, 75.58%, 98.75%, 63.44% and 98.76%, respectively. The corresponding values of RESENet model were 99.34% ( P<0.001), 99.57% ( P<0.001), 99.66% ( P<0.001), 90.20% ( P<0.001) and 99.66% ( P<0.001). Conclusion:Compared with the traditional ResNetV2 model, the artificial intelligence-assisted site identification model constructed by RESENNet, a hybrid neural network, shows significantly improved performance. This model can be used to monitor the integrity of the esophagogastroduodenoscopic procedures and is expected to become an important assistant for standardizing and improving quality of the procedures, as well as an significant tool for quality control of esophagogastroduodenoscopy.

Objective:To provide theoretical reference for the construction of effective prevention and control strategies. The study deeply investigates the impact of traumatic birth events on compassion fatigue and inner feelings of midwives.Methods:Fifteen midwives from five tertiary hospitals in Guangzhou were interviewed in depth by semi-structured interview method from April to June 2021. Colaizzi analysis and Nvivo12 plus software were used to analyze and integrate the data and extract themes.Results:Three main themes were extracted, including the characteristics of traumatic birth events (high incidence, sudden and dangerous, preventable and controllable); exacerbating compassion fatigue (reducing compassion satisfaction levels; exacerbating burnout; and aggravating traumatic stress responses); and exploring effective coping strategies (time required for adjustment, seeking stress release).Conclusions:As a strong stressor, traumatic birth events aggravate the symptoms of compassion fatigue in midwives. Managers should pay attention to the occupational exposure of traumatic childbirth events, actively guide midwives to make psychological adjustments. In addition, managers can increase social support and strengthen the ideological and political education of midwives, so that they have good stress tolerance and excellent professional psychological quality.

Objective:To study the safety and efficacy of endoscopic papillary balloon dilation for choledocholithiasis.Methods:A total of 60 patients with choledocholithiasis in Suqian People′s Hospital of Nanjing Drum Tower Hospital Group were included from January 2017 to December 2018 according to the inclusion and exclusion criteria. According to the random number table, the patients were divided into two groups: simple endoscopic papillary balloon dilation group (EPBD group, n=30) and endoscopic papillary sphincterotomy combined with balloon dilation group (ESBD group, n=30). Lithotripsy time, X-ray exposure time, one-time lithotripsy rate, lithotripsy rate, incidence of postoperative acute pancreatitis, intraoperative and postoperative bleeding rates were compared.Results:The time of stone extraction (8.5±2.4 min) in EPBD group was comparable with that of group ESBD (7.8±2.1 min) ( P=0.14). The time of X-ray exposure was 21.8±5.2 min in EPBD group and 19.7±6.3 min in ESBD group ( P=0.11). Stones were extracted at one time in all 60 patients, and no lithotripsy was conducted. The incidences of acute pancreatitis after endoscopic retrograde cholangiopancreatography(ERCP) in the two groups were both 6.67% (2/30). The intraoperative bleeding rates were 3.33% (1/30) and 10.00% (3/30) in EPBD group and ESBD group ( P=0.042), respectively. The rate of postoperative bleeding was 3.33% (1/30) in ESBD group ( P=0.035). No other recent complications occurred in the two groups. Conclusion:Endoscopic papillary balloon dilation alone is safe and effective in the treatment of choledocholithiasis.

PURPOSE: Asthma affects approximately 30 million patients in China; however, tiotropium data for Chinese patients is limited. This study aimed to assess the efficacy and safety of tiotropium in Chinese patients with moderate symptomatic asthma. METHODS: A post hoc subgroup analysis was conducted on 430 Chinese patients pooled from two 24-week, replicate phase 3 trials (NCT01172808 and NCT01172821), in which they received once-daily tiotropium 2.5 µg (Tio R2.5) or 5 µg (Tio R5) (n = 106 or 109, respectively), twice-daily salmeterol 50 µg (Sal 50) (n = 110), or placebo (n = 105), while maintaining inhaled corticosteroids (ICS). The co-primary endpoints assessed in week 24 were forced expiratory volume in 1 second (FEV1) peak0–3h response, trough FEV1 response, and responder rate as assessed using the Asthma Control Questionnaire (ACQ). RESULTS: For both FEV1 peak0–3h responses and trough FEV1 responses, the mean treatment differences were greater for Tio R2.5, Tio R5, and Sal 50 compared with placebo at 0.249 L, 0.234 L, and 0.284 L, and 0.172 L, 0.180 L, and 0.164 L, respectively (P< 0.001). The ACQ responder rate in placebo, Tio R2.5, Tio R5, and Sal 50 was 58.7%, 62.3%, 59.3%, and 69.1%, respectively. Furthermore, 11 (2.6%) of 430 patients had serious adverse events (Tio R5, n = 4; Tio R2.5, n = 1; Sal 50, n = 1; and placebo, n = 5). CONCLUSIONS: Once-daily tiotropium, as add-on to medium-dose ICS, was effective and well tolerated for Chinese patients with moderate symptomatic asthma, consistent with the main analysis.
Adrenal Cortex Hormones ; Adult ; Asian Continental Ancestry Group ; Asthma ; China ; Forced Expiratory Volume ; Humans ; Salmeterol Xinafoate ; Tiotropium Bromide

ObjectiveTo explore the feasibility and safety of preoperative cardiac rehabilitation (CR) nursing intervention in patients with severe valvular disease, and to evaluate the effect of preoperative exercise-mediated cardiac rehabilitation nursing on the clinical outcomes of patients after operation. MethodsFrom January to December of 2017, 108 patients with advanced valvular heart disease (AVHD) admitted in Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School were selected based on the diagnostic standard for AVHD. The AVHD patients should not be younger than 18 years old, left ventricular ejection fraction(LVEF) less than 40%, and need repair of interventricular septal perforation, resection of ventricular aneurysm and radiofrequency ablation of surgical atrial fibrillation simultaneously. Random number method was used to divide the patients into control group and cardiac rehabilitation nursing intervention group (CR group). Mitral and aortic valve lesions were the main types of valvular lesions in the two groups, and the principles of preoperative treatment were the same. Patients in the control group received routine nursing after admission. The patients in the observation group were evaluated by 6 minute walking test (6MWT) after admission. According to the distance of 6MWT, MOTO Med nursing intervention was carried out in gradeⅠ andⅡ. Frequency was once a day, 30 minutes each time, the first movement resistance was 1 kg, and was adjusted appropriately according to the individual situation. Exercise training and aerobic training were carried out for gradeⅢ andⅣ, with emphasis on lower limb muscles, abdominal muscles and ectopectoralis once a day for 20 minutes each time. ResultsThere was no significant difference in hospital stay, ICU stay time and mechanical ventilation time between the two groups (P＞0.05). The LVEF value of CR group was significantly higher than that of control group at the early stage after operation [(42.5±6.2) vs .(31.0±4.5),P＜0.001)]. The 6 MWT (P=0.009) and self-management(Barthel) score (P=0.001) of CR group were better than those of control group. There was no significant difference in quality of life between the two groups 30 days after operation(P＞ 0.05). ConclusionsPreoperative cardiac rehabilitation nursing intervention can effectively improve the cardiac function of patients with severe valvular disease early after operation, increase the early exercise tolerance of patients after operation, improve the early self-care ability of patients after operation, and help patients recover better and faster.

OBJECTIVETo observe the effects of conventional western medication and joss stick moxibustion combined with pricking and cupping for herpes zoster in acute stage, and to explore its analgesic mechanism.

METHODSSeventy patients with acute herpes zoster were randomized into an observation group (33 cases after 2 dropping) and a control group (34 cases after 1 dropping). Patients in the observation group were treated with joss stick moxibustion combined with pricking and cupping at localpoints for 7 times, once every other day. Oral acyclovir, vitamin Band mecobalamin tablets were applied in the control group for continuous 14 days, and interferon injection was used for continuous 6 days, etc. The herpes evaluation indexes of blister stopping time, scab time and decrustation time as well as pain intensity were observed before and after treatment. Peripheral serum substance P (SP) content of herpes local situation was detected. The comprehensive effects were evaluated.

RESULTSThe blister stopping time, scab time and decrustation time in the observation group were shorter than those in the control group (all<0.05). There was no statistical significance for pain relief degree between the two groups (>0.05). The pain beginning to ease time and duration time in the observation group were better than those in the control group (both<0.05). The contents of SP in the two groups decreased after treatment (both<0.01), and it was better in the observation group (<0.05). The total effective rate of the observation group after treatment was 87.9% (29/33), and that of the control group was 85.3% (29/34), which were not statistically significant (>0.05). The cured rate of the observation group was better than that of the control group [66.7% (22/33) vs 58.8% (20/34),<0.05].

CONCLUSIONJoss stick moxibustion combined with pricking and cupping are effective for herpes zoster, which have quicker and good analgesic effects than conventional western medication. Its mechanism may be related to reducing the content of SP more fast and to a larger degree.

Objective To assess the association of three polymorphisms in Megsin (rs1055901,rs1055902 and rs2689399) and susceptibility of IgA nephropathy in Asian population.Methods We conducted a comprehensive search of electronic CNKI,VIP,WangFang Data,CBM,Pubmed,Web of Science and Google Scholar database on the association between Megsin rs1055901,rs1055902 and rs2689399 polymorphism and susceptibility of IgA nephrology in Asian population (last search update on 2 May 2016).Stata 12.0 software was used to calculate the odds ratio (OR) and 95 ％ CI (confidence interval),as well as sensitivity and publication bias analyses.Results Six publications encompassing mine case-control studies were finally included,including 2 179 cases and 1 769 controls.Finally,no significant association between Megsin rs1055901 and rs1055902 polymorphism and IgA nephrology in Asian population was identified,while a significantly decreased risk of IgA nephrology for rs2689399 polymorphism,was identified in Asian population (G and C:OR=0.754,95％CI 0.592-0.961,P=0.022;GG and CC:OR=0.506,95％CI 0.287-0.892,P=0.019;GG and GC+CC:OR=0.551,95％CI 0.316-0.961,P=0.036).Conclusion Rs2689399 G allele and GG genotype of Megsin may be the protective factors for IgA nephropathy in Asian population.