The Heterogeneity of Symptom Burden and Fear of Progression Among Kidney Transplant Recipients: A Latent Class Analysis.

Purpose: Kidney transplant recipients (KTRs) may experience symptoms that increase their fear of progression (FoP), but a dearth of research examines the issue from a patient-centered perspective. Our study aimed to first determine the category of symptom burden, then to explore the differences in characteristics of patients in different subgroups, and finally to analyze the impact of symptom subgroup on FoP. Patients and Methods: Sociodemographic and Clinical Characteristics, Symptom Experience Scale, and Fear of Progression Questionnaire-Short Form were used. Latent class analysis was used to group KTRs according to the occurrence of symptoms. We used multivariate logistic regression to analyze the predictors of different subgroups. The differences in FoP among symptom burden subgroups were analyzed by hierarchical multiple regression. Results: Three subgroups were identified, designated all-high (20.5%), moderate (39.9%), and all-low (39.6%) according to their symptom occurrence. Multivariate logistic regression showed that gender, post-transplant time, per capita monthly income, and hyperuricemia were the factors that distinguished and predicted the all-high subgroup (P < 0.05). Hierarchical multiple regression showed that symptom burden had a significant effect on FoP (class1 vs class3: ß = 0.327, P < 0.001; class2 vs class3: ß = 0.104, P = 0.046), explaining the 8.0% variance of FoP (ΔR2 = 0.080). Conclusion: KTRs generally experience moderate or low symptom burden, and symptom burden is an influencing factor in FoP. Identifying the traits of KTRs with high symptom burden can help clinicians develop targeted management strategies and ease FoP of KTRs.

Development of a Helmet-Shape Dual-Channel RF coil for brain imaging at 54 mT using inverse boundary element method.

Very-low field (VLF) magnetic resonance imaging (MRI) offers advantages in term of size, weight, cost, and the absence of robust shielding requirements. However, it encounters challenges in maintaining a high signal-to-noise ratio (SNR) due to low magnetic fields (below 100 mT). Developing a close-fitting radio frequency (RF) receive coil is crucial to improve the SNR. In this study, we devised and optimized a helmet-shaped dual-channel RF receive coil tailored for brain imaging at a magnetic field strength of 54 mT (2.32 MHz). The methodology integrates the inverse boundary element method (IBEM) to formulate initial coil structures and wiring patterns, followed by optimization through introducing regularization terms. This approach frames the design process as an inverse problem, ensuring a close fit to the head contour. Combining theoretical optimization with physical measurements of the coil's AC resistance, we identified the optimal loop count for both axial and radial coils as nine and eight loops, respectively. The effectiveness of the designed dual-channel coil was verified through the imaging of a CuSO4 phantom and a healthy volunteer's brain. Notably, the in-vivo images exhibited an approximate 16-25 % increase in SNR with poorer B1 homogeneity compared to those obtained using single-channel coils. The high-quality images achieved by T1, T2-weighted, and fluid-attenuated inversion-recovery (FLAIR) protocols enhance the diagnostic potential of VLF MRI, particularly in cases of cerebral stroke and trauma patients. This study underscores the adaptability of the design methodology for the customization of RF coil structures in alignment with individual imaging requirements.

Two-dimensional liquid chromatography measurement of meropenem concentration in synovial fluid of patients with periprosthetic joint infection.

Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery. One potential treatment approach for PJI could be the combination of one-stage revision and intra-articular infusion of antibiotics. Meropenem is one of the commonly used intra-articular antibiotics in our institution. Determining the concentration of meropenem in the joint cavity could be crucial for optimizing its local application, effectively eradicating biofilm infection, and improving PJI treatment outcomes. In this study, we developed a simple, precise, and accurate method of two-dimensional liquid chromatography (2D-LC) for determining the concentration of meropenem in human synovial fluid. The method was then validated based on the guidelines of the Food and Drug Administration and the Chinese Pharmacopoeia. Meropenem showed good linearity in the range of 0.31-25.01 µg/mL (r ≥ .999). Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, and stability validation results were all within the acceptance range. This method has been successfully applied to the determination of synovial fluid samples from PJI patients, providing a useful detection method for meropenem therapeutic drug monitoring (TDM) in PJI patients.

Effects and Mechanisms of Electroacupuncture at Zhongwan （CV12） on Gastric Nociceptive Response Induced by Gastric Acid Stimulation in Rats / 中医杂志

ObjectiveTo observe the effects of electroacupuncture at Zhongwan （CV12） on gastric nociceptive response induced by gastric acid stimulation and explore the underlying mechanisms associated with nuclei of the medullary viscerosensory and visceral motor neurons. MethodsTwenty SD rats were given intragastric administration of 0.5 mol/L diluted hydrochloric acid （0.5 ml/100 g） to induce gastric nociceptive response induction. Eight rats were randomly selected to record the gastric slow wave （GSW） area under the curve， and extracellular discharge frequency of neurons in the nucleus of the solitary tract （NTS） and dorsal motor nucleus of the vagus nerve （DMV） before intragastric administration and at 1， 5， 10， 15， 20， 25， 30， 35， 40， 45， 50， 55， and 60 minutes after intragastric administration. The remaining 12 rats received electroacupuncture intervention at Zhongwan within 5 to 25 minutes after intragastric administration of diluted hydrochloric acid， with a duration of one minute. The GSW area under the curve and extracellular discharge frequency of NTS and DMV neurons were compared between the 1-minute intervals before and after electroacupuncture intervention. ResultsCompared to the baseline before intragastric administration， the area under the curve of GSW significantly increased at 1， 5， 10， 15， 20， and 25 minutes after intragastric administration， and the extracellular discharge frequency of excitatory neurons in the NTS （accounting for 90%， 57/63） significantly increased at 1， 5， 10， 15， 20， 25， 30， 35， and 40 minutes， both reaching peak values at 1 minute after intragastric administration （P＜0.01 or P＜0.05）. The extracellular discharge frequency of inhibitory neurons in the DMV （accounting for 91%， 20/22） showed a non-significant increase at 1 minute after intragastric administration （P＞0.05）， but significantly decreased at other timepoints （P＜0.05）. Compared to the baseline before electroacupuncture intervention， the GSW area under the curve and the extracellular discharge frequency of excitatory neurons in the NTS significantly decreased （P＜0.05）， while the extracellular discharge frequency of inhibitory neurons in the DMV showed no significant difference （P＞0.05）. ConclusionElectroacupuncture at Zhongwan can improve gastric nociceptive response induced by gastric acid stimulation， possibly by reducing the transmission of visceral sensation and decreasing the excitability of NTS neurons in the medulla.

Characterization and in vitro antibacterial activity of grass carp (Ctenopharyngodon idella) serum amyloid A.

Serum amyloid A (SAA) predominantly synthesized by hepatocytes is a classical acute phase protein and has been extensively studied in mammals. However, the studies on the structure and properties of fish SAA are limited although SAA genes have been cloned and identified from various fishes. In the present study, a cDNA of grass carp (Ctenopharyngodon idella) SAA (gcSAA) was cloned and characterized, displaying a high homology with its counterparts in vertebrates. gcSAA mRNA was expressed with highest abundance in the liver and its levels were increased by a 24-hour infection of Aeromonas hydrophila (A. hydrophila) for more than 5 folds in the intestine, 15 folds in the spleen, 75 folds in the head kidney and 100 folds in the liver, implying that it is an acute phase protein in grass carp. Subsequently, recombinant gcSAA protein (rgcSAA) was prepared from a prokaryotic expression system after codon optimization of its coding sequence. The direct antibacterial activity assay and the plate count assay disclosed that gcSAA inhibited the growth and survival of A. hydrophila but not Edwardsiella piscicida (E. piscicida) which both are common bacterial pathogens in aquaculture. The propidium iodide (PI) uptake assay confirmed the bactericidal property of gcSAA, showing that it is able to enhance the uptake of PI in A. hydrophila but not E. piscicida. These findings revealed the molecular features of gcSAA and its roles in host defense against bacterial infection.

An atypical two-component system, AtcR/AtcK, simultaneously regulates the biosynthesis of multiple secondary metabolites in Streptomyces bingchenggensis.

Streptomyces bingchenggensis is an industrial producer of milbemycins, which are important anthelmintic and insecticidal agents. Two-component systems (TCSs), which are typically situated in the same operon and are composed of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Here, an atypical TCS, AtcR/AtcK, in which the encoding genes (sbi_06838/sbi_06839) are organized in a head-to-head pair, was demonstrated to be indispensable for the biosynthesis of multiple secondary metabolites in S. bingchenggensis. With the null TCS mutants, the production of milbemycin and yellow compound was abolished but nanchangmycin was overproduced. Transcriptional analysis and electrophoretic mobility shift assays showed that AtcR regulated the biosynthesis of these three secondary metabolites by a MilR3-mediated cascade. First, AtcR was activated by phosphorylation from signal-triggered AtcK. Second, the activated AtcR promoted the transcription of milR3. Third, MilR3 specifically activated the transcription of downstream genes from milbemycin and yellow compound biosynthetic gene clusters (BGCs) and nanR4 from the nanchangmycin BGC. Finally, because NanR4 is a specific repressor in the nanchangmycin BGC, activation of MilR3 downstream genes led to the production of yellow compound and milbemycin but inhibited nanchangmycin production. By rewiring the regulatory cascade, two strains were obtained, the yield of nanchangmycin was improved by 45-fold to 6.08 g/L and the production of milbemycin was increased twofold to 1.34 g/L. This work has broadened our knowledge on atypical TCSs and provided practical strategies to engineer strains for the production of secondary metabolites in Streptomyces.IMPORTANCEStreptomyces bingchenggensis is an important industrial strain that produces milbemycins. Two-component systems (TCSs), which consist of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Coupled encoding genes of TCSs are typically situated in the same operon. Here, TCSs with encoding genes situated in separate head-to-head neighbor operons were labeled atypical TCSs. It was found that the atypical TCS AtcR/AtcK played an indispensable role in the biosynthesis of milbemycin, yellow compound, and nanchangmycin in S. bingchenggensis. This atypical TCS regulated the biosynthesis of specialized metabolites in a cascade mediated via a cluster-situated regulator, MilR3. Through rewiring the regulatory pathways, strains were successfully engineered to overproduce milbemycin and nanchangmycin. To the best of our knowledge, this is the first report on atypical TCS, in which the encoding genes of RR and HK were situated in separate head-to-head neighbor operons, involved in secondary metabolism. In addition, data mining showed that atypical TCSs were widely distributed in actinobacteria.

RVX-208, an inducer of Apolipoprotein A-I, inhibits the particle production of hepatitis B virus through activation of cGAS-STING pathway.

BACKGROUND: Previously, we have demonstrated that Apolipoprotein A-I (ApoA-I) could inhibit the secretion of Hepatitis B virus (HBV), suggesting that stimulation of ApoA-I may block particle production. In the present study, we evaluated the anti-HBV effect of RVX-208, a small-molecule stimulator of ApoA-I gene expression. METHODS: RVX-208 was used to treat HepG2.2.15 cell, a HepG2 derived cell line stably producing HBV virus. Real-time PCR was performed to examine the HBV DNA levels. Magnetic particles, which were coated with anti-HBS or anti-HBE antibody, were used to examine the HBsAg and HBeAg levels in the supernatant of cultured HepG2.2.15 cells in combination with the enzyme conjugates that were prepared with horseradish peroxidase labelled anti-HBS or anti-HBE antibody in a double antibody sandwich manner. RNA-seq, immunoblots and real-time PCR were used to analyze the functional mechanism of RVX-208. RESULTS: RVX-208 could elevate the ApoA-I protein levels in HepG2.2.15 cells. In the meantime, RVX-208 significantly repressed HBV DNA, HBsAg and HBeAg levels in the supernatants of HepG2.2.15 cells. RNA-seq data revealed that RVX-208 treatment not only affected the cholesterol metabolism, which is closely related to ApoA-I, but also regulated signalling pathways that are associated with antiviral immune response. Moreover, mechanistic studies demonstrated that RVX-208 could activate cGAS-STING pathway and upregulate the transcription of a series of interferons, pro-inflammatory cytokines and chemokines with antiviral potential that are at the downstream of cGAS-STING pathway. CONCLUSION: Our study demonstrated that RVX-208, an inducer of ApoA-I, could suppress HBV particle production through activation of cGAS-STING pathway.

[Pro-oxidation status of rotator cuff tissue and expression of Beclin-1 and mTOR in patients with rotator cuff injury].

OBJECTIVE: To explore pro-oxidative state of rotator cuff tissue and expression levels of Beclin-1 and mam-malian target of rapamycin(mTOR) in patients with acute and chronic rotator cuff injury, and then analyzed relationship between rotator cuff injury and oxidative stress and autophagy. METHODS: Forty patients with rotator cuff injury were seleceted from July 2019 to December 2020, and divided into male chronic injury group, male acute injury group, female chronic injury group, and female acute injury group, 10 patients in each group. All patients were performed rotator cuff repair under arthroscopy. The sample of tendon at the rotator cuff injury site of the patient was taken during operation, and total reactive oxygen species (ROS) and superoxide dismutase(SOD) were detected by detection kit;expression of Beclin-1 and mTOR mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western-blot was applied to detect protein expression of Beclin-1 and p-mTOR/mTOR. RESULTS: There were no significant difference in expression of ROS, SOD, Beclin-1mRNA and mTOR mRNA between male and female chronic injury groups, and between male and female acute injury groups (P>0.05); ROS, SOD and Beclin-1mRNA in male chronic injury group were higher than those in male chronic injury group, while mTOR mRNAand protein decreased (P<0.05);ROS, SOD and Beclin-1 mRNA in female chronic injury group were up-regulated compared with female acute injury group, while mTOR mRNA was down-regulated (P<0.05). CONCLUSION: Chronic rotator cuff injury is more likely to stimulate the pro-oxidation state of rotator cuff tissue than acute rotator cuff injury, which could up-regulating expression of autophagy factor Beclin-1 and down-regulating expression of mTOR. Therefore, patients with chronic rotator cuff injury may have higher levels of oxidative stress and autophagy.

The mediating effect of sense of coherence on the caregiver ability-caregiver burden relationship for caregivers of children with liver transplantation in China.

BACKGROUND: Caregivers of children who have had liver transplantation often experience chronic care stress. Previous studies have focused on caregivers' negative feelings (e.g., caregiver burden), but few studies have focused on caregivers' positive feelings (e.g., sense of coherence) and caregiver ability. OBJECTIVES: The study purpose was to investigate the status of the burden of caregivers of children with liver transplantation, and to explore the mediating role of sense of coherence between caregiver ability and caregiver burden. METHODS: There were 461 questionnaires collected from a tertiary-level hospital from caregivers of children who had liver transplantation from April to June 2022. Demographic data, Family Caregiver Task Inventory, Sense of Coherence Scale-13, and Zarit Burden Interview were used. The STROBE checklist was monitored. RESULTS: The average caregiver burden score was 32.19 ± 16.71. The distribution of caregiver burden levels was mild (42.52%), none (26.25%), moderate (24.95%), and severe (6.29%). Caregiver ability score was negatively correlated with caregiver burden score; however, sense of coherence score was negatively correlated with caregiver burden score. Caregiver ability partially mediated caregiver burden through sense of coherence (38.51%). CONCLUSION: The caregiver burden level was not heavy in general. Both positive and negative feelings were present in caregivers. Caregiver ability also reduced the caregiver burden through sense of coherence.

Fast detection of liver fibrosis with collagen-binding single-nanometer iron oxide nanoparticles via T1-weighted MRI.

SNIO-CBP, a single-nanometer iron oxide (SNIO) nanoparticle functionalized with a type I collagen-binding peptide (CBP), was developed as a T1-weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO-CBP exhibits 6.7-fold higher relaxivity compared to a molecular gadolinium-based collagen-binding contrast agent CM-101 on a per CBP basis at 4.7 T. Unlike most iron oxide nanoparticles, SNIO-CBP exhibits fast elimination from the bloodstream with a 5.7 min half-life, high renal clearance, and low, transient liver enhancement in healthy mice. We show that a dose of SNIO-CBP that is 2.5-fold lower than that for CM-101 has comparable imaging efficacy in rapid (within 15 min following intravenous injection) detection of hepatotoxin-induced liver fibrosis using T1-weighted MRI in a carbon tetrachloride-induced mouse liver injury model. We further demonstrate the applicability of SNIO-CBP in detecting liver fibrosis in choline-deficient L-amino acid-defined high-fat diet mouse model of nonalcoholic steatohepatitis. These results provide a platform with potential for the development of high relaxivity, gadolinium-free molecular MRI probes for characterizing chronic liver disease.

Identification of resistant sources from Glycine max against soybean cyst nematode.

Soybean cyst nematode (SCN, Heterodera glycines, HG) is one of the severe pests in plant-parasitic nematodes, which impairs root development and causes severe losses in soybean production worldwide. Breeding SCN-resistant cultivars is an important measure for securing harvests without affecting the environment, as can be done with pesticides. The majority of genetic resources for plant pest resistances are found in wild or closely related species which are often difficult to use in breeding due to crossing barriers or close linkage with unfavorable agronomic traits. In this study, 12 soybean cultivars were evaluated for their marker haplotype at the rhg1 and Rhg4 SCN resistance loci and their SCN resistance tested against multiple races in environmentally controlled bioassays. The results showed that all 12 cultivars displayed Peking-type resistance marker haplotypes and all of them proved to be resistant to multiple SCN races. These cultivars provide potential for improving H. glycines resistance of soybean as donor parent in breeding and can contribute to reduce SCN field populations as part of a sustainable agriculture management.

Consumer Preference for Virtual Reality Advertisements with Human-Scene Interaction: An Intermediary Based on Psychological Needs.

Consumption is undergoing a digital revolution brought about by virtual technology, and the emergence of virtual spokespersons has changed the pattern of advertising endorsement sales. Are virtual character spokespersons better than real celebrity spokespersons? This article aims to explore the relationships between different types of advertising spokespersons, different types of advertising scenarios, and consumers' purchase intentions. The results of 2 pilot experiments and 4 formal experiments show that compared with spokespersons by real people, virtual character spokespersons have a greater positive impact on consumers' purchase intentions, which is achieved through the mediating role of psychological need satisfaction. In addition, different advertising scenarios provided by virtual technology have a moderating effect on this process. This empirical study investigates the possible positive effects of virtual character spokesperson compared with real character spokesperson and expands the results of spokesperson category based on self-determination theory.

The use of human-derived feeder layers for the cultivation of transplantable human epidermal cell sheet to repair second degree burn wounds.

BACKGROUND AND OBJECTIVES: Human epidermal cell sheet (human-ECS) is a feasible treatment option for wound injury. Traditionally, researchers often use murine 3T3 fibroblast cells as feeder layer to support human epidermal cell sheet grafts, thus increase risk to deliver animal-borne infection. To overcome the potential risks involved with xenotransplantation, we develop human foreskin fibroblast cell as feeder layer culture system and investigate the effects of human-ECS on second-degree burn wound healing in mini-pig in order to develop more effective and safer therapies to enhance wound healing in human. MATERIALS AND METHODS: Human epidermal keratinocytes and fibroblasts were isolated from foreskin tissue and were co-cultured to manufacture human-ECS. The cell morphology was monitored with phase-contrast microscopy, the stem cell markers were assessed by flow cytometry, and by colony-forming efficiency (CFE) assay. The structure of human-ECS was observed by hematoxylin and eosin staining. Expression of cytokines in human-ECS was confirmed by enzyme-linked immunosorbent assay. Second-degree burn wounds were created on the dorsal of miniature pig to evaluate the effect of oil gauze, oil gauze combined with commercial epidermal growth factor (EGF) cream, and oil gauze combined with human-ECS. Wound healing rate, histological examination, and Masson staining were measured to observe the wound repair efficacy. Real-time PCR and Western blot were utilized to detect the expression level of EGF and interleukin 6 (IL-6). RESULTS: Stratified human-ECS with 6-7 layers of epidermal cells was successfully cultivated with human-derived feeder cells, in which epidermal cell highly expressed CD49f and CFE was 3% ± 0.45%. Application of human-ECS induced a higher wound healing rate than commerical EGF cream and oil gauze control. The expression of EGF in human-ECS group was higher than those in the other groups; however, the expression of IL-6 was significantly decreased at day 14 by human-ECS treatment group. CONCLUSIONS: Human-derived feeder cells are suitable for cultivation of human-ECS, avoiding pathogen transmission. Human-ECS could enhance second-degree burn wound healing, and its promoting effect involved secreting a variety of cytokines to regulate tissue reparative process.

Strategies to Improve the Oxygen Reduction Reaction Activity on Pt-Bi Bimetallic Catalysts: A Density Functional Theory Study.

Decreasing the level of use of Pt in proton exchange membrane fuel cells is of great research interest both academically and industrially. In this work, we systematically studied the oxygen reduction reaction (ORR) following the four-electron association mechanism at various Pt-Bi surfaces with density functional theory calculations. The results showed that the introduction of Bi changes the potential-determining step of ORR. Moreover, the hydroxy adsorption free energy (GOH*) can be used as a descriptor of ORR activity, and 0.74 eV is the ideal GOH* for it to reach its maximum. Notably, we also found that the tensile strain introduced by Bi and electron transfer between Pt and Bi synergize to modulate the d-band of Pt to contract, shift downward, and break the 5d96s1 valence electron configuration of Pt, and accordingly, PtBi(100), with the lowest d-band center, gives the best ORR activity, which is even slightly higher than that of Pt(111).

Correction of the pathogenic mutation in the G6PC3 gene by adenine base editing in mutant embryos / 中华血液学杂志

Objective: To determine whether the adenine base editor (ABE7.10) can be used to fix harmful mutations in the human G6PC3 gene. Methods: To investigate the safety of base-edited embryos, off-target analysis by deep sequencing was used to examine the feasibility and editing efficiency of various sgRNA expression vectors. The human HEK293T mutation models and human embryos were also used to test the feasibility and editing efficiency of correction. Results: ①The G6PC3(C295T) mutant cell model was successfully created. ②In the G6PC3(C295T) mutant cell model, three distinct Re-sgRNAs were created and corrected, with base correction efficiency ranging from 8.79% to 19.56% . ③ ABE7.10 could successfully fix mutant bases in the human pathogenic embryo test; however, base editing events had also happened in other locations. ④ With the exception of one noncoding site, which had a high safety rate, deep sequencing analysis revealed that the detection of 32 probable off-target sites was <0.5% . Conclusion: This study proposes a new base correction strategy based on human pathogenic embryos; however, it also produces a certain nontarget site editing, which needs to be further analyzed on the PAM site or editor window.

Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus disease 2019 (version 2023) / 中华创伤杂志

The condition of patients with severe traumatic brain injury (sTBI) complicated by corona virus 2019 disease (COVID-19) is complex. sTBI can significantly increase the probability of COVID-19 developing into severe or critical stage, while COVID-19 can also increase the surgical risk of sTBI and the severity of postoperative lung lesions. There are many contradictions in the treatment process, which brings difficulties to the clinical treatment of such patients. Up to now, there are few clinical studies and therapeutic norms relevant to sTBI complicated by COVID-19. In order to standardize the clinical treatment of such patients, Critical Care Medicine Branch of China International Exchange and Promotive Association for Medical and Healthcare and Editorial Board of Chinese Journal of Trauma organized relevant experts to formulate the Chinese expert consensus on clinical treatment of adult patients with severe traumatic brain injury complicated by corona virus infection 2019 ( version 2023) based on the joint prevention and control mechanism scheme of the State Council and domestic and foreign literatures on sTBI and COVID-19 in the past 3 years of the international epidemic. Fifteen recommendations focused on emergency treatment, emergency surgery and comprehensive management were put forward to provide a guidance for the diagnosis and treatment of sTBI complicated by COVID-19.

Application of single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy / 中华胰腺病杂志

Objective:To explore the clinical efficacy and safety of single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy.Methods:The clinical data of 45 patients who underwent laparoscopic pancreaticoduodenectomy with the procedures of single-layer with full thickness in Second Hospital of Hebei Medical University from Jan 2020 to Jan 2022 were retrospectively collected and compared with 45 matched patients with traditional two-layer pancreaticojejunostomy.Results:The laparoscopic pancreaticoduodenectomy procedures were successfully performed in all the 90 cases. The mean operation time (285.6±92.4 minutes) and the media pancreaticojejunostomy time 20(15, 35) minutes) of the single-layer with full thickness pancreaticojejunostomy group were shorter than those of the two-layer pancreaticojejunostomy group [the mean operation time: 317.0±85.5 minutes, the media pancreaticojejunostomy time: 46(30, 58) minutes] with significantly statistical differences (all P value<0.05). There were no significantly statistical differences on intraoperative blood loss, the postoperative complications or hospital stay between the two groups. Conclusions:Compared with traditional pancreaticojejunostomy, the single-layer with full thickness of duct-to-mucosa pancreaticojejunostomy is simple and safe, which has the advantage of easy manipulation and less time-consuming and can be recommended for laparoscopic procedures.

Analysis of the clinical characteristics of 69 cases of occupational melanosis / 中国职业医学

Objective To summarize the clinical characteristics of patients with occupational melanosis. Methods Diagnostic data of 69 patients with occupational melanosis was analyzed using retrospective analysis. Results The main occupational hazards for the 69 patients with occupational melanosis were coal tar, petroleum and its fractionated products, pigments and dyes and their intermediates, rubber additives and rubber products. The median length of occupational exposure and disease latency were 8.0 and 6.0 years, respectively, with a highly positive correlation between them (Spearman correlation coefficients=0.962, P<0.01). Skin lesions were mainly found on exposed areas such as the face-to-neck and limbs, prevalence of 94.2% and 75.4% respectively. And 78.3% of patients had skin lesion on more than two sites. The lesions were mostly in the form of irregular flakes (59.4%), with a gray-black color (44.9%). About 43.5% of patients experienced skin itching. Complete blood count, liver function, and kidney function were all within normal ranges. Skin biopsy results showed that epidermal hyperkeratosis, thinning of the spinous layer, liquefaction degeneration of basal cells, increased superficial dermal melanocytes, and infiltration of lymphocytes, histiocytes, and melanocytes around the blood vessels. Reflectance confocal microscopy (RCM) detection showed focal liquefaction degeneration of basal cells in the lesions, with a significant infiltration of melanocytes and inflammatory cells in the dermal papillae and superficial layers. Conclusion The primary target organ of occupational melanocytes is the skin, and no damage to other organs was identified thus far. Results from skin biopsies and RCM examinations can be used for differential diagnosis.

Efficacy and Safety of Fruquintinib Combined with Sintilimab in Treatment of Advanced Microsatellite Stable Colorectal Cancer / 肿瘤防治研究

Objective To investigate the clinical efficacy and safety of fruquintinib combined with sintilimab in the treatment of advanced microsatellite stable (MSS) colorectal cancer. Methods A retrospective study of 44 patients with MSS colorectal cancer treated with fruquintinib and sintilimab was conducted.The patients were divided into the fruquintinib alone (n=22) and fruquintinib combined with sintilimab (n=22) groups.The treatment regimen was as follows: The patients in the fruquintinib alone group consumed oral fruquintinib capsules at 5 mg/d once for three consecutive weeks with a one week stop in 28 day cycles.The patients in the fruquintinib combined sintilimab group were injected intravenously with sintilimab (200 mg) once per three weeks, and fruquintinib was used in the same manner as the fruquintinib alone group. Results The objective response rate (ORR) of the fruquintinib alone group was 9.09%, the disease control rate (DCR) of the fruquintinib alone group was 45.45%.The ORR of the fruquintinib combined with sintilimab group was 18.18%, and the DCR was 63.64%.The median PFS of the fruquintinib alone and fruquintinib combined with sintilimab groups were 4.4 months (IQR: 2.1-8.2) and 6.7 months (IQR: 3.9-12.6), respectively (χ2=4.372, P=0.037).Most of the adverse reactions during the treatment of the two groups were grades 1-2.In addition, no significant difference in the incidence of adverse reactions was found between two groups (P > 0.05). Conclusion Compared with fruquintinib alone, fruquintinib combined with sintilimab in the treatment of patients with MSS colorectal cancer after the failure of standard treatment has better clinical efficacy, and adverse drug reactions can be controlled.

Research progress of ionizable lipid nanoparticles for siRNA delivery / 药学学报

Small interfering RNA (siRNA) is the initiator of RNA interference and inhibits gene expression by targeted degradation of specific messenger RNA. siRNA-mediated gene regulation has high efficiency and specificity and exhibits great significance in the treatment of diseases. However, the naked or unmodified siRNA has poor stability, easy to degrade by nuclease, short half-life, and low intracellular delivery. As an emerging non-viral nucleic acid delivery system, ionizable lipid nanoparticles play an important role in improving the druggability of siRNA. At present, one siRNA drug based on ionizable lipid nanoparticles has been approved for the treatment of rare disease. This review introduces the research progress in ionizable lipid nanoparticles for siRNA delivery, focusing on the effect of each component of lipid nanoparticles on the efficiency of siRNA-mediated gene silencing, which provides new references for the studies on ionizable lipid nanocarriers for siRNA delivery.