Objective To investigate the clinical efficacy and safety of nivolumab(PD-1 inhibitor)in combination with lenvatinib and FOLFOX regimen[5-fluorouracil(5-FU),oxaliplatin(L-OHP),and calcium folinate(LV)]in the treatment of intermediate and advanced hepatocellular carcinoma(HCC)via hepatic arterial infusion chemotherapy(HAIC).Methods A total of 160 patients with intermediate and advanced HCC admitted to the Second Affiliated Hospital of Guilin Medical University from January 2021 to January 2023 were randomly divided into the control group and the observation group,with 80 patients in each group,using a random number table.The control group received once-daily oral lenvatinib and intravenous carrizumab infusions for 12 weeks as part of transcatheter arterial chemoembolization(TACE)therapy.The observation group was administered with FOLFOX regimen via HAIC chemotherapy,plus intravenous infusion of carrizumab for 12 weeks and once-daily oral lenvatinib.All the patients were followed up regularly.The clinical efficacy was evaluated using the mRECIST criteria.The objective response rate(ORR),disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and incidence of adverse reactions were compared between the two groups.Results There were no significant differences in the objective response rate and incidence of adverse reactions between the groups.The disease control rate,overall survival,and progression-free survival in the observation group were significantly higher than those in the control group(P<0.05).Conclusions The FOLFOX-HAIC regimen in combination with nivolumab and lenvatinib is safe and effective for the treatment of intermediate and advanced HCC,without adverse reactions.It can prolong the overall survival and progression-free survival,and improve the patient's quality of life.

Background and Aims:Postoperative intra-abdominal infection(PIAI)is a common postoperative complication in abdominal surgery and a challenging issue worldwide,with a treatment failure rate of 68.3％and an in-hospital mortality rate as high as 40.8％.The key to managing this condition is early control of the infection source,debridement and adequate drainage.Delayed control of the infection source is an independent risk factor for predicting treatment failure.Many PIAI lesions are located deep within the abdominal cavity,lacking optimal routes for percutaneous drainage,and the risks and difficulties of reoperation are significant.Thus,controlling the infection source in PIAI is a difficult task.Here,the authors report the management of 4 PIAI patients treated with nephroscopic debridement and catheter irrigation and drainage via the sinus tract,aiming to provide clinical insights and references. Methods:The clinical data of 4 patients undergoing nephroscopic debridement,catheter irrigation and drainage for PIAI from October 2020 to September 2022 in the Department of Hepatobiliary and Pancreatic Surgery of the Second Affiliated Hospital of Guilin Medical University were retrospectively analyzed.Key techniques of nephroscopic management of PIAI were summarized and contextualized with relevant literature. Results:The 4 PIAI cases included a right-sided retroperitoneal abscess after catheter drainage for severe acute pancreatitis,a hepatic abscess at the liver raw surface after right hemihepatectomy,bile leakage and secondary duodenal fistula after laparoscopic choledocholithotomy and T-tube drainage,and a pancreatic abscess at the pancreatic raw surface after distal pancreatectomy with splenectomy.All patients underwent nephroscopic debridement and catheter irrigation and drainage via the sinus tract:guidewires were inserted into the drainage sinus tract,followed by a minimally invasive expansion drainage kit and nephroscopy;pus was irrigated out,and pus moss was clamped out with foreign body forceps under nephroscopy.Then,irrigation drainage tubes were placed under the guidance of the guidewire,and continuous irrigation and drainage were performed.The 4 patients underwent a total of 5 nephroscopic debridement and catheter irrigation and drainage procedures,with one case requiring two operations.The preoperative catheterization time ranged from 14 to 58 d,with an average of 38.4 d.One patient concurrently underwent choledochoscopy for stone extraction and biliary drainage via the T-tube sinus tract.The operative time ranged from 30 to 115 min,with an average of 67.4 min.Aside from one case of minor intraoperative bleeding,which stopped after injecting diluted norepinephrine solution into the sheath and blocking the sheath,there were no surgical complications in the other three cases.The postoperative drainage tube duration ranged from 7 to 30 d,with an average of 20.75 d.After treatment,all PIAI lesions disappeared,and no recurrence was observed during follow-up,which ranged from 16 to 40 months. Conclusion:Nephroscopic debridement and catheter irrigation and drainage via the sinus tract for PIAI is simple,feasible,and safe,allowing for direct visualization to avoid organ damage.It is effective in removing pus and necrotic tissue,replacing drainage tubes,and can be repeatedly performed with high efficiency and remarkable results.This method is particularly suitable for patients with postoperative abdominal drainage tube obstruction combined with encapsulated intra-abdominal fluid collections.

Objective:To research and design a negative pressure environment that can be applied in container type of biological isolation shelter,so as to meet the stable negative pressure environment and dynamic intelligent regulation of pressure difference in the container during multimodal transportation,especially under air freight conditions.Methods:The design specifications and research achievements of pressure differences of negative pressure isolation equipment for infectious diseases at home and abroad were comprehensively analyzed.And then,one kind of power-distributed ventilation system without air duct was designed to achieve.The preseted pressure redundancy,real-time monitoring of sensors and dynamic follow-up of pressure were used to realize stable and intelligent regulation of negative pressure within the container during air freight.Results:After testing,the pressure differences of each region of the"three regions and two channels"included clean region,buffer region,contamination region,medical staff passage and patient passage within container type of biological isolation shelter under the negative pressure environment could meet the preseted requirements.The values of pressure differences at the outside of room of clean region,the toilet of clean region,the toilet of clean region of the second dressing room of the buffer region,the contamination region of the first dressing room of the buffer region,the toilet of contamination region and the outside of the room of contamination region were respectively 34.2,38.8,-8.0,-31.7,-15.1 and-44.6.The conditions of the pressure differences within each region of container,which dynamically met the requirements of Biosafety Level-Ⅲ(BSL-3)laboratory,were tested through the sensors,and intelligent display and control equipment that deployed inside of container.Conclusion:The stable negative pressure environment and intelligent regulation for pressure difference in each region of the container can take container to have more high biosafety characteristics,which can effectively ensure the safe transportation of whole region for patients with severe infectious diseases,and the transport and treatment under air freight condition.

ObjectiveTo investigate the pharmacodynamic characteristics and explore the molecular mechanism of Honghua oral liquid （HOL） in relieving neuropathic pain （NP）. MethodHealthy male SD rats were randomly assigned into sham group， model group， low-， medium-， high-dose （0.5， 1.0， 2.0 mL·kg^-1·d^-1， respectively） HOL groups， and a positive drug （pregabalin， 25 mg·kg^-1·d^-1） group， with 6 rats in each group. Spinal nerve ligation （SNL） of L5 was conducted in other groups except the sham group. Drug administration was performed 3 days after the SNL surgery for 2 consecutive weeks， and samples were collected after the end of the administration. During the treatment period， the mechanical pain threshold and cold pain threshold were determined to measure the pain-relieving effect of HOL. Transcriptome sequencing was performed on hippocampal tissue samples from the sham， model， and high-dose HOL groups， and differentially expressed genes between the sham group and the model group as well as the model group and HOL high-dose group were obtained. After pathway enrichment analysis， we selected the targets which were closely related to neuroinflammation for validation， and predicted the specific binding sites of the major active components in HOL with the targets through molecular docking. In addition， the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-10 （IL-10） were determined by enzyme-linked immunosorbent assay （ELISA） to evaluate the effect of HOL on neuroinflammation in NP rats. ResultCompared with the sham group， SNL decreased the mechanical pain threshold and cold pain threshold （P<0.05）. Compared with the model group， HOL recovered the mechanical pain threshold and cold pain threshold （P<0.05）. The transcriptome data showed that 376 differentially expressed genes （DEGs） were identified between the model group and the sham group， including 124 upregulated genes and 252 downregulated genes， and 194 DEGs between the model group and the high-dose HOL group， including 33 upregulated genes and 161 downregulated genes. Among them， insulin-like growth factor 1（IGF1）， matrix metallopeptidase-2 （MMP-2）， matrix metallopeptidase-14 （MMP-14）， erb-B2 receptor tyrosine kinase 2 （ERBB2）， and integrin subunit alpha 5 （ITGA5） associated with NP were selected for further validation. The Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） results showed that compared with the sham group， the modeling up-gurelated the mRNA levels of the above five molecules in the hippocampus （P<0.01）. Compared with model group， HOL down-regulated the mRNA levels of these molecules （P<0.01）. The molecular docking results showed that the main active components of safflower， hydroxysafflor yellow A， kaempferol， and quercetin， formed stable hydrogen bonds with the amino acid residues of IGF1， MMP-2， MMP-14， ERBB2， and ITGA5. The enzyme-linked immunosorbent assay（ELISA） results showed that compared with those in the sham group， the serum levels of TNF-α and IL-10 were out of balance in the model rats （P<0.01）. Compared with the model group， HOL lowered the level of the pro-inflammatory cytokine TNF-α （P<0.01） and elevated that of the anti-inflammatory cytokine IL-10 （P<0.05）. ConclusionHOL exerts analgesic effect on SNL rats by inhibiting neuroinflammation.

Objective:To observe the changes of macular microvascular structure and macular pigment density (MPOD) in eyes with macular edema (ME) secondary to retinal vein occlusion (RVO), and preliminarily analyze their correlation.Methods:A prospective clinical study. A total of 62 eyes of 62 patients with monocular RVO secondary ME (RVO-ME) diagnosed in the Ophthalmology Hospital of Xi'an No.1 Hospital from July 2020 to May 2021 were included in this study. There were 33 males with 33 eyes, 29 females with 29 eyes. The age was 58.30±12.15 years. The course of disease from the onset of symptoms to medical treatment was 12.29±7.65 days. All patients underwent best corrected visual acuity (BCVA), optical coherence tomography angiography (OCTA) and MPOD test. BCVA examination was performed using a standard logarithmic visual acuity chart, which was converted to logarithm of minimum angle of resolution (logMAR). The vascular density (VD), vascular skeletal density (SD), foveal avascular area (FAZ) and central macular thickness (CMT) of the superficial retinal capillary plexus (SCP) in the range of 3 mm×3 mm in the macular area of bilateral eyes were measured by OCTA. MPOD was measured by heterochromatic scintillation photometry. Bilateral eyes passed examination in 37 cases. The eyes of 25 patients failed to pass the test. The changes of macular VD, SD, FAZ area, CMT and MPOD between the affected eyes and the contralateral eyes were compared. The MPOD of the affected eye and the contralateral eye was compared by paired t test. FAZ area, CMT, VD, SD, and logMAR BCVA were tested by paired Wilcoxon signed rank sum test. Spearman rank correlation test was used to analyze the correlation between macular blood flow density (VD, SD) and foveal morphology (FAZ area, CMT) with logMAR BCVA and MPOD. Results:Compared with contralateral eyes, VD ( Z=-5.981) and SD ( Z=-6.021) were decreased, FAZ area ( Z=-2.598) and CMT ( Z=-6.206) were increased, and the differences were statistically significant ( P<0.05). In 37 patients who passed MPOD test in bilateral eyes, the MPOD value of the affected eye was lower than that of the contralateral eye, and the difference was statistically significant ( t=-2.930, P<0.05). Compared with the affected eye which failed to pass the MPOD detection, macular VD ( Z=-2.807) and SD ( Z=-2.460) were increased, FAZ area ( Z=-4.297) and CMT ( Z=-3.796) were decreased in the affected eye which passed the MPOD test, and the differences were statistically significant ( P<0.05). Correlation analysis showed that logMAR BCVA in the affected eye was negatively correlated with macular VD and SD ( r=-0.298, -0.461; P<0.05), which was positively correlated with FAZ area and CMT ( r=0.487, 0.789; P<0.05). MPOD in the affected eye was negatively correlated with logMAR BCVA ( r=-0.344, P<0.05). MPOD in the contralateral eye was positively correlated with CMT ( r=0.358, P<0.05). Conclusions:The VD and SD of macular SCP are decreased, FAZ area is enlarged, CMT is thickened, and MPOD is decreased in RVO-ME eyes. MPOD is negatively correlated with logMAR BCVA.

Objective:To explore the integration path of medical resources in regional medical consortium, find out the problems affecting the process of integration, and put forward relevant suggestions.Methods:Methods According to the purposive sampling and combined with grounded theoretical research methods, semi-structured interviews were conducted with 73 government officials, heads and backbones of medical institutions in different regions of a city from August to November 2019. The data obtained from semi-structured interviews were analyzed by using grounded theory, and the path framework of medical resource integration in regional medical consortium was constructed through open coding, spindle coding and selective coding.Results:Four key links of medical resource integration in the regional medical alliance were sorted out, namely, integration prerequisites, integration strategies, support conditions, and integration methods, which together constituted the main axis of the theoretical framework. In addition, integration methods were affected by integration prerequisites, integration strategies and support conditions. The four factors and integration willingness served as influencing factors to exert impact on the integration tendency.Conclusions:The integration of medical resources in the medical alliance is a systematic project, which emphasizes the organic and overall governance of each key link, and the interaction between various elements will affect the final effect of medical resource integration.

Birth cohort is an important observational study which can continuously and dynamically collect the exposure changes and health outcomes from gametophyte development to adolescence and even old age. However, because of its complex design and difficult implementation, how to construct birth cohort with high quality and high efficiency is the main difficulty faced by epidemiologists at home and abroad. In 2016, China National Birth Cohort was officially launched. The network and information technology were used to explore, and a set of "cloud-based information platform" was established to support this queue construction, containing 16 units in China. After four years of development, the platform has formed a complete set of programs about the construction of cohort information platform, which including recruitment and follow-up management of participants, real-time data interaction, queue quality control, multi-level authority management and function division. The relevant design framework and functional elements provide the references to the future information construction of large-scale birth cohort and even population-based research in China.

The importance of gut microbes to human health has gradually attracted attention. With the use of animal models, it has been revealed that maternal microbes during pregnancy could influence their children's health outcomes through shaping their microbial composition and regulating the development of their metabolic and immune system. However, the physiological mechanism of the human body is more complex and is affected by the interaction of multiple factors. The research results obtained from animal models are often inconsistent with human studies. At present, the influence of maternal intestinal microbes during pregnancy on the microbial colonization in their offspring and on a series of children's health outcomes is still unclear. Establishing a sub-cohort to detect the microbiome of the women across pregnancy and of their offspring, and further to integrate with variety of environmental and behavioral exposures can better provide reliable support for the research on the mechanism of children's health and diseases. This paper briefly introduces the research objectives, content, progress, strength and limitations of the sub-cohort study.

Objective:To explore the consistency of peripheral whole blood and venous serum procalcitonin (PCT) levels, and the value of peripheral whole blood PCT in evaluating pediatric bacterial infection.Methods:This multicenter cross-sectional parallel control study was conducted in 11 children′s hospital. All the 1 898 patients older than 28 days admitted to these hospitals from March 2018 to February 2019 had their peripheral whole blood and venous serum PCT detected simultaneously with unified equipment, reagent and method. According to the venous serum PCT level, the patients were stratified to subgroups. Analysis of variance and chi-square test were used to compare the demographic characteristics among groups. And the correlation between the peripheral blood and venous serum PCT level was investigated by quantitative Pearson correlation analysis.The PCT resultes were also converted into ranked data to further test the consistency between the two sampling methods by Spearman′s rank correlation test. Furthermore, the ranked data were converted into binary data to evaluate the consistency and investigate the best cut-off of peripheral blood PCT level in predicting bacterial infection.Results:A total of 1 898 valid samples were included (1 098 males, 800 females),age 27.4(12.2,56.7) months. There was a good correlation between PCT values of peripheral whole blood and venous serum ( r=0.97 , P<0.01). The linear regression equation was PCT?venous serum=0.135+0.929×PCT peripheral whole blood. However, when stratified to 5 levels, PCT results showed diverse and unsatisfied consistency between the two sampling methods ( r=0.51-0.92, all P<0.01). But after PCT was converted to ordinal categorical variables, the stratified analysis showed that the coincidence rate of the measured values by the two sampling methods in each boundary area was 84.9%-97.1%. The dichotomous variables also showed a good consistency (coincidence rate 96.8%-99.3%, Youden index 0.82-0.89). According to the severity of disease, the serum PCT value was classified into 4 intervals（<0.5、0.5-<2.0、2.0-<10.0、≥10.0 μg/L）, and the peripheral blood PCT value also showed a good predictive value (AUC value was 0.991 2-0.997 9). The optimal cut points of peripheral whole blood PCT value 0.5、1.0、2.0、10.0 μg/L corresponding to venous serum PCT values were 0.395, 0.595, 1.175 and 3.545 μg/L, respectively. Conclusions:There is a good correlation between peripheral whole blood PCT value and the venous serum PCT value, which means that the peripheral whole blood PCT could facilitate the identification of infection and clinical severity. Besides, the sampling of peripheral whole blood is simple and easy to repeat.