The sample delivery method is one of the key steps in implementing serial femtosecond crystallography research using X-ray free-electron lasers. Serial femtosecond crystallography can effectively capture the ultrafast dynamic processes of biological molecules, such as protein conformational changes and intermediate states in chemical reactions. It is of great significance for scientists to better understand the structure and function of biological molecules, reveal the mechanisms of life activities, and provide important technical means for drug development and biotechnology. When conducting experiments at X-ray free-electron laser beamline station, it is crucial to transport the samples to the region where it interacts with the free-electron laser pulses. The choice of suitable sample delivery method plays a decisive role in the sample consumption and experimental efficiency, and it is also an important factor for the success or failure of the experiment. This article reviews the latest research progress and future development directions of sample delivery methods in serial crystallography. It also introduces commonly used sample delivery methods and their applicable ranges, aiming to provide reference and guidance for scientists engaged in serial crystallography research. The sample transport methods of free electron lasers mainly include liquid injection and fixed target sample transport. The liquid injection method is achieved through various liquid sample injectors. The aqueous solution is driven by a peristaltic pump on high performance liquid chromatography (HPLC) into a sample storage, and the aqueous solution pushes the piston in the sample storage to extrude the sample solution into the sample transport pipeline, and finally sprays it out through the nozzle to reach the XFEL interaction region. For micro-nano crystals,3 preparation methods are introduced, including free interface diffusion method, seeding method, and batch crystallization, and characterization methods are also introduced. For the requirements of high sample transmission efficiency and low sample consumption, a gas-based liquid flow transport method is introduced, which is based on the principle of focusing the sample jet by coaxial gas to form a jet with a small diameter and fast flow rate. At the same time, the extended double flow focusing nozzle and mixed injection nozzle are briefly described. For samples in viscous media, a high viscosity liquid injection device is introduced, and the advantages and disadvantages of different media are explained and exemplified. In addition, the principle and example of electrostatic spinning injector and piezoelectric driven droplet injection technology applied to low-velocity serial crystallography experiments are also introduced. For the above liquid injection methods, a characterization method using a coaxial microscope or side-view microscope to measure the diameter and stable length of the liquid flow is introduced. Compared with the liquid injection method, the fixed target method is to fix the crystal on a support chip with a periodic array structure, and collect data through scanning. The working principle, sample environment, support materials, etc. of the fixed target method are briefly introduced in the article. With the advancement and development of technologies such as free electron lasers and detectors, various sampling methods for serial crystallography are constantly being innovated and optimized. By selecting appropriate sample delivery methods, it will be possible to improve experimental efficiency, reduce sample consumption, and open up new possibilities for researchers in the field of structural biology of biomacromolecules.

Objective To investigate the risk factors for bronchopulmonary dysplasia (BPD) in preterm infants,and to establish a risk prediction model. Methods A total of 120 preterm infants who were admitted to the neonatal intensive care unit of Shanghai Children's Hospital from January to December 2022 were included. According to the diagnostic criteria for BPD released by the National Institute of Child Health and Human Development in 2018,they were divided into a non-BPD group (84 infants) and a BPD group (36 infants). The clinical data of the infants and their mothers were compared between the two groups. The univariate analysis and the stepwise multivariate regression analysis were used to identify the risk factors for BPD and establish a risk prediction model. Results The results showed that a gestational age of<28 weeks,duration of noninvasive respiratory support,comorbidity with infectious pneumonia,and chorioamnionitis in the mother were independent risk factors for BPD in preterm infants (P<0.05). A nomogram model for predicting the development of BPD was established based on the risk factors,with an area under the receiver operating characteristic curve of 0.93,and the calibration curve of this nomogram had a slope of about 1. The goodness-of-fit test indicated the model fitted well (x2=8.287,P=0.406). Conclusions A gestational age of<28 weeks,duration of noninvasive respiratory support,comorbidity with infectious pneumonia,and chorioamnionitis in the mother are independent risk factors for BPD in preterm infants.

In this study， name， origin， producing areas， harvesting time and processing methods of ancient Alismatis Rhizoma were systematically researched by consulting the literature of ancient herbs， medical and prescription books， so as to provide a basis for the development of famous classical formula containing this herb. According to textual research， the main base of ancient Alismatis Rhizoma was Alisma plantago-aquatica and A. orientale. A. canaliculatum and A. gramineum and other genera were sometimes used as the source of Alismatis Rhizoma， there was a confusion of medicinal varieties. The earliest producing area of Alismatis Rhizoma was in today's Henan province， and later Hanzhong， Shaanxi province， became the high-quality producing area of Alismatis Rhizoma. Since the Ming dynasty， its production area expanded to Fujian. In the Qing dynasty， Jian'ou in Fujian was the authentic production area of Alismatis Rhizoma. In the period of the Republic of China， Sichuan and Jiangxi were added to the production areas of Alismatis Rhizoma. Based on the research results， it is suggested that the dried tubers of A. orientale from Fujian and Jiangxi or A. plantago-aquatica from Sichuan should be used in the famous classical formulas. In ancient times， Alismatis Rhizoma was processed by wine， but most of the standards and specifications in modern times are no longer included the processing specifications of Alismatis Rhizoma with wine. Although salt-processed Alismatis Rhizoma is commonly used in modern times， it didn't become one of the main processing methods until the Qing dynasty. According to the relevant national documents， it is suggested that Alismatis Rhizoma without clear processing requirements in famous classical formulas should be used as raw products， and the formulas with processing requirements should be selected as processed products such as salt and wine according to the meaning of the formulas.

Objective: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE)-hepatic arterial infusion chemotherapy (HAIC)-targeted-immune quadruple therapy in patients with intermediate and advanced-stage hepatocellular carcinoma (HCC). Methods: 101 patients with intermediate and advanced stage HCC were enrolled according to the inclusion and exclusion criteria, and then they were divided into a combination group and a control group. Patients in the combination group was treated with TACE-HAIC-targeted-immune quadruple therapy, while the control group was only treated with TACE therapy. The overall survival (OS), progression-free survival (PFS), and treatment-related adverse reactions were statistically analyzed in the two groups of patients. Statistical analysis was carried out by t-test, χ² test, rank sum test, Kaplan-Meier curve, log-rank test, Cox regression (or proportional hazards model) analysis according to different data. Results: The tumor objective response rate and disease control rate as evaluated by mRECIST 1.1 criteria in the combination group were 80% and 94%, respectively, which were significantly higher than those in the control group, 41.2% (P<0.001) and 74.5% (P=0.007). The OS and PFS of the combination group were 15.6 months [95%CI 11.3-NA ] and 8.8 months [95%CI 6.9-12.0], respectively, which were significantly better than the control group at 6.1 months [95%CI 5.3-6.6] (P<0.001) and 3.2 months [95%CI 3.0-3.6] (P<0.001). Gastric ulcer incidence was significantly higher in the combination group (9/50, 18%) than that in the control group (2/51, 3.9%) (P=0.023). Conclusion TACE-HAIC-targeted-immune quadruple therapy is a more effective treatment mode for intermediate and advanced-stage HCC than TACE alone, and attention should be paid to the monitoring of target immune-related adverse reactions.
Humans ; Carcinoma, Hepatocellular/pathology* ; Chemoembolization, Therapeutic ; Liver Neoplasms/pathology* ; Retrospective Studies ; Infusions, Intra-Arterial ; Treatment Outcome

Based on the systematic retrieval and the reported components of Sojae Semen Nigrum and Sojae Semen Praeparatum, this study conducted in-depth analysis of conversion of components in the fermentation process, and discussed types and possible mec-hanisms of conversion of chemical components, so as to provide the basis for studying technology, medicinal ingredients and quality standards. According to the analysis, there is a certain degree of conversion of nutrients(like protein, sugar, lipid), bioactive substances(like isoflavones, saponins, γ-aminobutyric acid) and other substances(like nucleosides, melanoids, biamines, etc) in the process of fermentation.
Chromatography, High Pressure Liquid ; Fermentation ; Isoflavones/analysis* ; Semen/chemistry* ; Soybeans

The historical evolution， fermentation technology and key links of Sojae Semen Praeparatum （SSP） were sorted out by consulting ancient books and modern literature， and the influencing factors and control methods of quality were analyzed and summarized in order to provide reference for the quality control of SSP. After analysis， it was found that in the fermentation process of SSP， fermentation strains， miscellaneous bacteria， temperature and humidity were all important factors affecting the quality of SSP. The condition control of "post fermentation" process has been paid more attention to in the past dynasties. In addition， the delicious SSP recognized in ancient times should be made from mold fermentation， and the breeding and application of fermented mold may be the key point to solve the quality problem of SSP. Therefore， based on the evaluation indexes of SSP in the past dynasties， it is of great significance to study and optimize the technological conditions such as strain， temperature and humidity in depth to improve the quality of SSP.

As a common disease worldwide, alcoholic liver injury is caused by long-term or excessive intake of alcohol and triggers cell death due to alcohol metabolism and reactive oxygen species(ROS)-mediated cytotoxicity. Wangshi Baochi(WSBC) Pills have been widely adopted in clinical practice for evacuating stasis, resolving turbidity, clearing heat, tranquilizing mind, invigorating sto-mach, promoting digestion, purging fire and removing toxin. This study aimed to investigate the efficacy of WSBC Pills in dispelling the effect of alcohol and protecting against acute alcoholic liver/stomach injury in mice, and preliminarily investigate its possible mole-cular mechanism. The results found that the preventive treatment with WSBC Pills contributed to elevating the activity of alcohol dehydrogenase(ADH) and its expression in liver and shortening the time required for sobering up of mice with acute alcoholic liver injury. The staining of liver pathological sections as well as the detection of serum aspartate aminotransferase(AST) and alanine aminotransferase(ALT) and liver ROS levels revealed that WSBC Pills protected the liver by reducing serum AST and ALT. It suppressed oxidative stress-induced liver injury by lowering liver ROS and elevating superoxide dismutase(SOD), and the liver-protecting effect was superior to that of silibinin. Western blot assay confirmed that WSBC Pills inhibited the oxidative stress by up-regulating SOD1 and NAD(P)H: quinone oxidoreductase 1(NQO-1). In addition, WSBC Pills lowered the ROS level to protect against the acute alcoholic stomach injury in mice. The findings have suggested that WSBC Pills alleviated the acute alcoholic liver/stomach injury in mice by increasing ADH and resisting oxidative stress.
Animals ; Chemical and Drug Induced Liver Injury ; Ethanol ; Liver/metabolism* ; Liver Diseases, Alcoholic ; Mice ; Oxidative Stress ; Stomach

Objective To evaluate the clinical value of holographic image navigation in urological laparoscopic and robotic surgery.Methods The data of patients were reviewed retrospectively for whom accepted holographic image navigation laparoscopic and robotic surgery from Jan.2019 to Dec.2019 in Beijing United Family Hospital and other 18 medical centers,including 78 cases of renal tumor,2 cases of bladder cancer,2 cases of adrenal gland tumor,1 cases of renal cyst,1 case of prostate cancer,1 case of sweat gland carcinoma with lymph node metastasis,1 case of pelvic metastasis after radical cystectomy.All the patients underwent operations.In the laparoscopic surgery group,there were 27 cases of partial nephrectomy,1 case of radical prostatectomy,2 cases of radical cystectomy and 2 cases of adrenalectomy.In the da Vinci robotic surgery group of 54 cases,there were 51 cases of partial nephrectomy,1 case of retroperitoneal lymph node dissection,1 case of retroperitoneal bilateral renal cyst deroofing and 1 case of resection of pelvic metastasis.There were 41 partial nephrectomy patients with available clinical data for statistic,with a median age of 53.5 years (range 24-76),including 26 males and 15 females.The median R.E.N.A.L score was 7.8 (range 4-11).Before the operation,the engineers established the holographic image based on the contrast CT images and reports.The surgeon applied the holographic image for preoperative planning.During the operation,the navigation was achieved by real time fusing holographic images with the laparoscopic surgery images in the screen.Results All the procedures had been complete uneventfully.The holographic images helped surgeon in understanding the visual three-dimension structure and relation of vessels supplying tumor or resection tissue,lymph nodes and nerves.By manipulating the holographic images extracorporeally,the fused image guide surgeons about location vessel,lymph node and other important structure and then facilitate the delicate dissection.For the 41 cases with available clinical data including 23 cases of robotic-assisted partial nephrectomy and 18 cases of laparoscopic nephrectomy,the median operation time was 140 (range 50-225) min,the median warm ischemia time was 23 (range 14-60) min,the median blood loss was 80(range 5-1 200) ml.In the robotic surgery group,the median operation time was 140 (range 50-215)min,the median warm i schemia time was 21 (range 17-40)min,the median blood loss was 150(range 30-1 200)ml.In the laparoscopic surgery group,the median operation time was 160(range 80-225)min,the median warm ischemia time was 25 (range 14-60)min,the median blood loss was 50 (range 5-1 200) ml.All the patients had no adjacent organ injury during operation.There were 2 cases with Clavien Ⅱ complications.One required transfusion and the other one suffered hematoma post-operation.However,the tumors were located in the renal hilus for these 2 cases and the R.E.N.A.L scores were both 11.Conclusions Holographic image navigation can help location and recognize important anatomic structures during the surgical procedures..This technique will reduce the tissue injury,decrease the complications and improve the success rate of surgery.

Introduction: Diabetic foot infection is often associated with high morbidity, disability and poor quality of life. This study focuses on the demography, the number of repetitive surgery and length of stay in hospital of patients with diabetic foot infection. Method: This is a retrospective observational study. Patients who were admitted to the Orthopaedic ward of Hospital Segamat (HS), Johor, Malaysia from January 2016 to December 2018 and required surgical intervention were included in the study. Data was collected from the computer system of HS and medical notes of patients. Results: 35.6% of the total orthopaedic emergency surgeries performed were for patients with diabetic foot infection, 25% of the surgical procedures performed were major amputations of lower limb and 40% of the patients with diabetic foot infection required more than one surgical operation. Discussion: The demographics of the patients is consistent with the demographics of Malaysia where majority of them are Malays followed by Chinese, Indians and others. Despite being only 10% of total admission to the department, this group of patients contributed to 35.6% of the total emergency surgeries performed. The amputation rate in the centre is comparable to the other local studies. The average length of stay in hospital was found to be shorter compared to overseas due to different rehabilitation protocols.

OBJECTIVE: To investigate the effect of chidamide on the killing activity of NK (Natural killer cell, NK) cells targeting K562 cells and its related mechanism. METHODS: K562 cells were pretreated with chidamide at different concentrations and cocultured with NK cells at different effect-target ratios. The killing effect of chidamide on K562 cells by NK cells, the expression of natural killer group 2 member D (NKG2D) ligands and apoptosis rate of K562 cells were detected by flow cytometry. RESULTS: The killing sensitivity of NK cells to K562 cells could be enhanced by chidamide. The expression of ULBP2 on K562 cell surface could be up-regulate, however, the expression of ULBP1 and MICA/MICB showed no statistically difference as compared with control group. Chidamide showed no obvious cytotoxicity to K562 cells. CONCLUSION Chidamide can significantly improve killing efficiency of NK cells on K562 cells, which may be related to the up-regulation of ULBP2 expression.
Aminopyridines ; Benzamides ; GPI-Linked Proteins ; Histocompatibility Antigens Class I ; Humans ; Intercellular Signaling Peptides and Proteins ; K562 Cells ; Killer Cells, Natural ; immunology ; NK Cell Lectin-Like Receptor Subfamily K