Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Objective:To measure the retinal structural and functional parameters of adult Macaca fascicularis, and explore the similarity of the retinal structural and functional parameters between non-human primates and normal human retinas.Methods:Six eyes of 3 5-year-old adult Macaca fascicularis were examined by in vivo detection including color fundus photography, retinal optical coherence tomography (OCT) and electroretinogram (ERG) to determine the thickness of the inner/outer retina at the fovea and 1 000/2 000 μm away from the nasal, temporal, superior and inferior regions of the fovea, the thickness of the retinal nerve fiber layer (RNFL), the area of optic disc, the area of optic cup, the area ratio of cup to disc and the biological parameters of flash ERG.Differences in the above parameters between left and right eyes were analyzed.The similarity of parameters between Macaca fascicularis and human was compared with reference to published literature.The use and care of animals complied with the Regulation on the Management of Experimental Animals.The study protocol was approved by the Institutional Animal Care and Use Committee of Hubei Topgene Biotechnology (NO.IACUC-2019-012). Results:The foveal thickness, optic disc area, cup-disc area ratio, and average RNFL thickness in normal adult Macaca fascicularis were (252.31±4.79)μm, (1.89±0.05)mm 2, 0.14±0.01, and (103.53±0.58)μm, respectively.The b-wave amplitude of dark-adapted 0.01 ERG was (66.75±7.29)μV.The a- and b-wave amplitudes of dark-adapted 3.0 ERG response were (57.15±15.01) and (122.10±25.51)μV, respectively.The a- and b-wave amplitudes, the amplitude of oscillation potentials, and the latency of dark-adapted 10.0 ERG response were (72.98±20.14)μV, (131.67±13.78)μV, (49.98±10.08)μV, and (30.02±5.76)ms, respectively.The a- and b-wave amplitudes of light-adapted 3.0 ERG were (9.16±2.75) and (40.43±5.57)μV, respectively.The latency and the amplitude of the light-adapted 30 Hz flicker was (26.61±1.19)ms and (24.72±5.10)μV, respectively.There was no significant difference in the parameters between left and right eyes (all at P>0.05). The retinal thickness in central fovea, mean RNFL thickness, waveform and amplitude of ERG of Macaca fascicularis were similar to normal human. Conclusions:The structure and function of the retina of adult Macaca fascicularis are similar to those of normal humans.As a laboratory animal for preclinical drug research, in vivo studies of Macaca fascicularis can refer to normal human retinal parameters.

Objective To investigate the relationship between Kirsten rat sarcoma viral oncogene homolog(KRAS),neuroblastoma viral oncogene RAS homolog(NRAS),V-raf murine sarcoma viral oncogene homo-log B(BRAF),human epidermal growth factor receptor 2(HER2)gene mutations and microsatellite instabili-ty(MSI)status and clinicopathological features in patients with colorectal cancer.Methods The clinical data of 226 patients with colorectal cancer treated in the hospital from October 2019 to March 2022 were collected.Next-generation sequencing technology was used to detect KRAS,NRAS,BRAF,HER2 gene mutations and MSI status.Immunohistochemistry was used to evaluate the mismatch repair system(MMR)status.Multiva-riate Logistic regression analysis was used to analyze the relationship between KRAS,NRAS,BRAF,HER2 gene mutations and clinicopathological features.Results Among 226 colorectal cancer patients,the mutation frequencies of KRAS,NRAS,BRAF and HER2 were 54.89％,5.3％,8.4％and 1.8％,respectively.The fre-quency of KRAS mutation in mucinous adenocarcinoma was higher than that in common adenocarcinoma(P＜0.05).The risk of KRAS mutation in right colon cancer was increased(OR=2.145,P=0.012).NR AS gene mutation was more frequent in left colon and rectal cancer(P＜0.05).The frequency of BRAF gene mu-tation was higher in poorly differentiated and microsatellite instability-high(MSI-H)colorectal cancer(P＜0.05),and the risk of BRAF gene mutation in the right colon was increased(OR=2.844,P=0.042).HER2 gene amplification mutation showed distant metastasis(P＜0.05).KRAS mutations were mutually exclusive with NRAS,BRAF and HER2 amplification mutations(P＜0.05).MSI-H was more frequent in the right co-lon(P＜0.05).Of the 226 cases,10 cases were defective mismatch repair(dMMR)/MSI-H,8 cases were dM-MR/microsatellite stable,and 5 cases were proficient mismatch repair/MSI-H.There was a moderate agree-ment between dMMR and MSI-H(Kappa=0.575).Conclusion KRAS,NRAS,BRAF,HER2 and MSI sta-tus are associated with clinicopathological features in patients with colorectal cancer.Combined detection of KRAS,NRAS,BRAF,HER2 and MSI can provide more accurate and effective data to guide the treatment and prognosis of patients.

Objective:Hypoxia is an important cause of chemotherapy resistance in gastric cancer.However,little is known about the growth of gastric cancer under purely hypoxia conditions.This study aims to study the effect of hypoxia on the growth patterns of gastric cancer cells and explore the response of gastric cancer cells to the chemotherapeutic drug 5-fluorouracil(5-FU)in a hypoxic environment. Methods:Gastric cancer cells MKN45 were cultured under 1%oxygen hypoxia and conventional air conditions.An intervention group with the addition of the chemotherapeutic drug 5-FU was also established.The proliferation and apoptosis of gastric cancer cells under different oxygen conditions and intervention groups were detected using the cell counting kit-8(CCK-8)method,JC-1 mitochondrial membrane potential assay,and Annexin-V/PI double staining method.Cell cycle changes were detected by flow cytometry,and mitochondrial changes were detected using electron microscopy. Results:In the absence of 5-FU intervention,compared with the normoxia group,the hypoxia group showed higher rates of early and late apoptosis and higher cell death rates as indicated by the JC-1 mitochondrial membrane potential assay,Annexin-V/PI double staining,and CCK-8 results.Flow cytometry results showed that the cell cycle was arrested in the G0/G1 phase without progression.Electron microscopy revealed more severe mitochondrial destruction.However,with 5-FU intervention,the hypoxia group showed lower apoptosis rates,more cell cycle progression,and less mitochondrial destruction compared with the normoxia group. Conclusion:Hypoxic environments promote apoptosis and even death in gastric cancer cells,but hypoxia counteracts the efficacy of the chemotherapeutic drug 5-FU,which may contribute to 5-FU chemotherapy resistance.

Objective:To evaluate the safety of a novel nanoparticle neurotrophic factor complex for intraocular application in non-human primates.Methods:Nanoparticles incorporated with ciliary neurotrophic factor (NP-CNTFs) were produced utilizing nanotechnology.Three adult male cynomolgus macaques were included and intravitreally injected with 10 μl NP-CNTFs at a concentration of 1 μg/μl into one of the two eyes, and these three eyes were designated as the NP-CNTFs group.The contralateral eyes received the same volume of phosphate buffered saline and were designated as the control group.Before the injection and on days 3 and 7 after the injection, routine clinical examinations of the anterior segment were performed to evaluate the ocular clinical symptoms such as conjunctival congestion, anterior chamber flare and cells.The fundus condition was observed by fundus photography.The morphological structure and thickness of retinas were detected by spectral domain-optical coherence tomography (SD-OCT).The use and care of animals were in accordance with the Guide for the Care and Use of Laboratory Animals issued by the National Institutes of Health and the standards of Association for Assessment and Accreditation of Laboratory Animal Care.The study protocol complied with the ethics of laboratory animal welfare and was approved by Hubei Topgene Biotechnology Co., Ltd.(No.IACUC-2019-012).Results:The NP-CNTFs prepared in this study had a particle size of (317±3)nm, a polydispersity index of 0.042±0.015, and a zeta potential of (-38.9±0.7)mV, and exhibited relatively good stability, bioavailability, and biocompatibility.Clinical examinations revealed that the clinical manifestations of conjunctival congestion, anterior chamber flare and cells were slightly more obvious in the NP-CNTFs group at 3 days after injection compared to the control group, but basically returned to normal at 7 days after injection.The scores of anterior-segment clinical symptoms of the NP-CNTFs and control group were (2.67±0.88) and (1.00±0.58) at 3 days after injection, and (0.67±0.33) and (0.33±0.33) at 7 days after injection, respectively, with no statistical differences between them ( t=2.50, 1.00; both at P>0.05).Fundus photography showed normal fundus in both groups at 7 days after injection with no abnormal changes including vitreous opacity, vitreous hemorrhage, retinal hemorrhage or papilloedema.SD-OCT showed no significant histological changes in the retinas at 7 days after injection in both groups.The retinal nerve fiber layer thickness of the NP-CNTFs and control group were (107.67±0.88) and (111.00±3.22)μm, respectively, and the macular foveal thickness of the two groups were (255.67±2.03) and (254.67±3.84)μm, respectively, with no statistical differences between them ( t=1.43, 0.50; both at P>0.05). Conclusions:The complex NP-CNTFs shows good safety for intraocular application in cynomolgus macaques.

Objective:To investigate the protective effects of an anti-inflammatory mixture on acute lung injury (ALI) induced by sepsis in rats, as well as its possible mechanisms.Methods:A total of 40 Sprague-Dawley (SD) rats were randomly divided into the sham group, septic ALI model group (model group), 3-methyladenine (3-MA) control group, and anti-inflammatory mixture pretreatment group, with 10 rats in each group. Cecal ligation and perforation (CLP) was performed to reproduce a septic ALI model. The rats in the sham group only underwent opening and closing the abdomen without perforation and ligation. Both groups were given saline gavage and intraperitoneal injection for 3 consecutive days before surgery. The 3-MA control group was given intraperitoneal injection of saline and autophagy inhibitor 3-MA 15 mg/kg for 3 consecutive days before modeling. The anti-inflammatory mixture pretreatment group was given 8.8 mL/kg of anti-inflammatory mixture by gavage [the composition of anti-inflammatory mixture: rhubarb 15 g (after the next), coptis chinensis 15 g, baical skullcap root 12 g, magnoliae cortex 12 g, dahurian patrinia herb 30 g] and saline intraperitoneal injection for 3 consecutive days before modeling. The rats in each group were anesthetized 24 hours after surgery and died due to abdominal aortic blood collection. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum inflammatory cytokines interleukins (IL-1β and IL-6). Lung tissue was taken and then the bronchoalveolar lavage fluid (BALF) was collected, and the levels of IL-1β and IL-6 were detected by ELISA. Lung wet/dry weight (W/D) ratio was measured. After hematoxylin-eosin (HE) staining, the histopathological changes of the lungs were observed under light microscopy. Western blotting was used to detect the expression of autophagy markers microtubule-associated protein 1 light chain 3-Ⅱ/Ⅰ (LC3-Ⅱ/Ⅰ) and Beclin-1 protein in lung tissue. Autophagosomes in lung tissue were observed with transmission electron microscopy.Results:Compared with the sham group, the rats in the model group exhibited severe destruction of lung tissue structure, with significant infiltration of inflammatory cells, the lung W/D ratio and the levels of IL-1β and IL-6 in serum and BALF were significantly increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein were down-regulated, the autophagosomes were more. The rats in the 3-MA control group exhibited more severe lung tissue injury as compared with the model group, the lung W/D ratio and the levels of inflammatory cytokines in serum and BALF were further increased, the expressions of LC3-Ⅱ/Ⅰ and Beclin-1 protein still showed a decrease tendency as compared with the sham group, and the autophagosomes were less than that in the model group. Compared with the model group, the anti-inflammatory mixture pretreatment group showed milder lung tissue injury with a minimal amount of inflammatory cell infiltration, the lung W/D ratio was significantly reduced (7.07±1.02 vs. 11.33±1.85, P < 0.05), the levels of IL-1β and IL-6 in both serum and BALF were significantly decreased [IL-1β (ng/L): 26.04±3.86 vs. 40.83±5.46 in serum, 17.75±2.02 vs. 26.86±4.32 in BALF; IL-6 (ng/L): 91.28±10.15 vs. 129.44±13.05 in serum, 76.06±7.51 vs. 120.91±7.47 in BALF, all P < 0.05], and the ratio of LC3-Ⅱ/Ⅰ and Beclin-1 protein expression were significantly increased [LC3-Ⅱ/Ⅰ ratio: 1.23±0.02 vs. 0.60±0.02, Beclin-1 protein (Beclin-1/GAPDH): 2.37±0.33 vs. 0.62±0.05, both P < 0.05]. Furthermore, an increase in the number of autophagosomes was observed. Conclusion:The anti-inflammatory mixture improves lung injury in rats with sepsis induced by CLP and reduce inflammation levels, potentially through upregulation of Beclin-1-mediated autophagy.

Atheriosclerosis mainly occurs in middle-aged and elderly people, as well as in obese individuals. It is closely associated with the occurrence and progression of coronary heart disease, peripheral vascular disease, and stroke, severely affecting human health. 18F-NaF is commonly used for PET/CT imaging and has excellent performance in plaque imaging in atheriosclerosis. It can image the plaque calcification during the early stage, thereby assessing the plaque and making reasonable predictions for the prognosis. This article provides a review of the application of 18F-NaF PET/CT in the imaging of calcified plaques in atheriosclerosis.

Sleep deprivation (SD) has a profound impact on the central nervous system, resulting in an array of mood disorders, including depression and anxiety. Despite this, the dynamic alterations in neuronal activity during sleep deprivation have not been extensively investigated. While some researchers propose that sleep deprivation diminishes neuronal activity, thereby leading to depression. Others argue that short-term sleep deprivation enhances neuronal activity and dendritic spine density, potentially yielding antidepressant effects. In this study, a two-photon microscope was utilized to examine the calcium transients of anterior cingulate cortex (ACC) neurons in awake SD mice in vivo at 24-hour intervals. It was observed that SD reduced the frequency and amplitude of Ca2+ transients while increasing the proportions of inactive neurons. Following the cessation of sleep deprivation, neuronal calcium transients demonstrated a gradual recovery. Moreover, whole-cell patch-clamp recordings revealed a significant decrease in the frequency of spontaneous excitatory post-synaptic current (sEPSC) after SD. The investigation also assessed several oxidative stress parameters, finding that sleep deprivation substantially elevated the level of malondialdehyde (MDA), while simultaneously decreasing the expression of Nuclear Factor erythroid 2-Related Factor 2 (Nrf2) and activities of Superoxide dismutase (SOD) in the ACC. Importantly, the administration of gallic acid (GA) notably mitigated the decline of calcium transients in ACC neurons. GA was also shown to alleviate oxidative stress in the brain and improve cognitive impairment caused by sleep deprivation. These findings indicate that the calcium transients of ACC neurons experience a continuous decline during sleep deprivation, a process that is reversible. GA may serve as a potential candidate agent for the prevention and treatment of cognitive impairment induced by sleep deprivation.

Objective:Continuous glucose monitoring (CGM) technology is used to compare the advantages of insulin degludec (IDeg) as a basal insulin regimen compared with insulin glargine (IGlar) in the treatment of adult type 1 diabetes mellitus.Methods:30 adult patients with T1DM admitted to Heji Hospital Affiliated to Changzhi Medical College from September 2019 to December 2020 were screened. According to the random number table method, the patients were randomly divided into two groups (insulin degludec group and insulin glargine group) at a ratio of 1∶1, respectively treated with IDeg, IGlar and aspartate insulin for 12 weeks. The main outcome measures were the coefficient of variation of blood glucose (CV), mean amplitude of glycemic excursions (MAGE), time in range (TIR), time above range (TAR) and time below range (TBR). The secondary outcome measures were mean blood glucose (MBG), standard deviation of blood glucose (SD), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h BG), hemoglobin A1c (HbA 1c), means of daily differences (MOOD), and the frequency of hypoglycemic events. Results:At 12 weeks of treatment, the HbA 1c, FPG, 2 h BG, MBG, SD, CV and MAGE of insulin degludec group were lower than those of insulin glargine group, with statistically significant difference (all P<0.05). The TIR in the insulin degludec group was significantly higher than that in the insulin glargine group [73(63, 75)% vs 43(28, 63)%, P<0.001], and the TAR was lower than that in the glycerine group [25(17, 23)% vs 35(33, 64)%, P=0.003]. From the curve spectrum of blood glucose level of the two groups, the stability of blood glucose in the insulin degludec group was better than that in the insulin glargine group. After 12 weeks of treatment, 8 cases (8/15) in insulin degludec group had HbA 1c<7.0%, and 4 cases (4/15) in insulin glargine group had HbA 1c<7.0%, without statistically significant difference ( P=0.264). There were 7 cases (7/15) in the insulin degludec group and 1 case (1/15) in the insulin glargine group who achieved high quality blood glucose control, with statistically significant difference ( P=0.035). At the 12th week of outpatient follow-up, the incidence of nocturnal hypoglycemic events in insulin degludec group was significantly lower than that in insulin glargine group (4/15 vs 11/15, P=0.027). Conclusions:Compared with insulin glargine, insulin degludec can achieve higher blood glucose compliance rate, lower blood glucose level and reduce blood glucose fluctuations in patients with type 1 diabetes.