Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

BACKGROUND:Iron overload refers to excessive accumulation of iron in the body,which can cause pathological changes in various tissues.At present,the molecular mechanism and potential gene targets related to iron overload in osteoarthritis still need to be further studied and explored. OBJECTIVE:To analyze the key genes of iron overload in osteoarthritis by means of bioinformatics and verify them in animal experiments,so as to provide a new idea for preventing and treating osteoarthritis from the perspective of iron overload. METHODS:GEO database and GeneCards database were used to screen out genes associated with osteoarthritis and genes associated with iron overload.Then,the intersection of the two was taken to obtain a collection of genes commonly associated with osteoarthritis and iron overload.GO and KEGG enrichment analyses were used to screen the functions and pathways of these genes.To further investigate the interactions between these genes,a protein-protein interaction network was constructed and five computational methods of Cytoscape software were utilized to identify the Hub genes for iron overload in osteoarthritis.Finally,12 male Sprague-Dawley rats were divided into osteoarthritis group and normal group,with 6 rats in each group.A knee osteoarthritis model was established by the modified Hulth method in the osteoarthritis group.The expression of Hub genes in the knee joint of rats in each group was detected by PCR. RESULTS AND CONCLUSION:(1)A total of 51 genes associated with iron overload were identified in osteoarthritis.GO enrichment analysis showed that these genes were mainly involved in cytokine receptor binding,chemokine receptor binding,cytokine activity,growth factor receptor binding and oligosaccharide binding.(2)KEGG enrichment analysis showed that genes associated with iron overload in osteoarthritis was mainly involved in tumor necrosis factor signaling pathway and lipid and atherosclerosis signaling pathway.(3)The protein-protein interaction network was constructed,and five Hub genes of iron overload,intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6,were obtained by further analysis.Animal experiments verified that there were significant differences in the expression of the above Hub genes in the rat knee joint between the control group and the experimental group(P<0.05).(4)All these findings show that intercellular cell adhesion molecule-1,tumor necrosis factor superfamily member 11,myelocytomatosis oncogene,janus kinase 2,and interleukin 6 can be used as the Hub genes of iron overload in osteoarthritis,which are expected to become new targets for the prevention and treatment of osteoarthritis.

Acute Gelsemium poisoning is a systemic disease primarily affecting the central nervous system and respiratory symptoms caused by the ingestion of a substantial amount of Gelsemium within a short period. It manifests as sudden onset and rapid progression, primarily caused by accidental ingestion due to misidentification, and posing significant health risks. The compilation of the Technical Plan for Emergency Health Response to Acute Gelsemium Poisoning describes in detail the specialized practice and technical requirements in the process of handling acute Gelsemium poisoning, including accident investigation and management, laboratory testing and identification, in-hospital treatment, and health monitoring. The guidelines clarify key procedures and requirements such as personal protection, investigation elements, etiology determination, medical rescue, and health education. The key to acute Gelsemium poisoning investigation lies in promptly identifying the toxin through exposure history, clinical manifestations, and sample testing. Because there is no specific antidote for Gelsemium poisoning, immediate removal from exposure, rapid elimination of the toxin, and respiratory monitoring are critical on-site rescue measures. Visual identification of food or herbal materials, followed by laboratory testing to determine Gelsemium alkaloids in samples is a rapid effective screening method. These guidelines offer a scientific, objective, and practical framework to support effective emergency responses to acute Gelsemium poisoning incidences.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To investigate whether brown adipose tissue-derived exosomes(BAT-exos) could ameliorate endothelial cell injury by activating Pink1-Parkin pathway-mediated mitophagy.Methods:Endothelial cell injury was induced with angiotensin Ⅱ(Ang Ⅱ) to establish a cellular injury model. Exosomes were isolated from both brown adipose tissue and white adipose tissue and characterized by transmission electron microscopy(TEM), nanoparticle tracking analysis(NTA), fluorescence labeling, and Western blot. Cell viability was assessed using the CCK-8 assay, and apoptosis rates were determined by flow cytometry. Levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, and IL-8 were measured by ELISA. Mitochondrial autophagy was assessed by immunofluorescence colocalization, and protein expression levels of Pink1, Parkin, and LC3 Ⅱ/I were determined by Western blot.Results:Ang Ⅱ induced endothelial cell apoptosis, activated inflammatory responses, and suppressed mitophagy, as evidenced by decreased expression of mitophagy-related proteins. Following the successful characterization of BAT-exos, we found that BAT-exos activated mitophagy and alleviated endothelial cell injury, whereas white adipose tissue-derived exosomes(WAT-exos) inhibited mitophagy and exacerbated injury. Mechanistically, BAT-exos targeted the Pink1-Parkin signaling pathway to activate mitophagy.Conclusion:BAT-exos markedly improve endothelial cell injury by activating mitophagy through the Pink1-Parkin pathway, providing new insights and potential therapeutic targets for cardiovascular diseases.

Objective:To explore the clinical efficacy of periosteal induction technique combined with transfer of sural neurovascular flap in treatment of post-traumatic osteomyelitis of calcaneus with soft tissue defect.Methods:Clinical data, from January 2017 to December 2022, of 17 patients in the Army Institute for Traumatic Orthopaedics, the 920th Hospital of Joint Service Force of the Chinese People’s Liberation Amy with post-traumatic calcaneal osteomyelitis combined with soft tissue defect were retrospectively studied. The patients were 11 males and 6 females, with 46.5 (17-68) years in average. All patients received surgical treatment with periosteal induction technique in 2 phased surgies. Thorough debridement, antibiotics blended bone cement filling and wound coverage with sural neurovascular flap were carried out in phase-I surgery; The phase-II surgery were performed at 6-8 weeks after infection control to remove bone cement and then to transfer bone grafts for periosteal induction. After surgery, flap healing and infection control were observed. The infection control, pain improvement, recovery of ankle function and improvement of quality of life were evaluated by comparison of following parameters before and after surgery per phase: infection indicators [white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)], Visual Analogue Scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and MOS 36-item Short form Health Survey (SF-36, Boston Institute of Health, USA).Results:All 17 patients completed the two-phased surgical treatment, with an average interval of 9.4 (8-16) weeks between phase-I and phase-II surgery. All patients were included in the postoperative follow-up of 25.8 (13-40) months. After debridement in phase-I surgery, the sizes of soft tissue defect were found at 3.0 cm×2.0 cm-6.0 cm×8.0 cm. All flaps survived from the reconstructive surgery of sural neurovascular flap. Postoperative distal flap necroses occurred to 4 patients but all healed after further debridement. Recurrence of postoperative infection occurred to 2 patients and the infection control was achieved after the phase-I rescue surgery. Good outcomes without recurrence of infection were achieved after phase-II surgery. The postoperative follow-up at 1 year after phase-II surgery showed a statistically significant improvement of infection in blood indicators and reductions in VAS score, AOFAS ankle-hindfoot score and SF-36 score in comparison with those before surgery ( P<0.05). In addition to WBC, there were also significant differences in pairwise comparisons between each group at different time points ( P<0.05). Conclusion:In the treatment of post-traumatic calcaneal osteomyelitis with soft tissue defect, a combination of periosteal induction technique and sural neurovascular flap is beneficial to infection control, bone defect reconstruction, recovery of ankle function and improvement of quality of life.

To analyze the transmission characteristics of newly reported HIV-infected students aged ≥18 years in Nanjing City from 2016 to 2022 and provide evidence for AIDS publicity and intervention among young students. The pol region sequences of newly reported HIV-infected students and non-student HIV-infected individuals in Nanjing City from 2016 to 2022 were collected, and the BLAST tool was used to search the published global non-Nanjing reported HIV infection sequences in the LANL HIV database. The basic molecular transmission network and regional molecular transmission network were constructed using the HIV-TRACE in a pairwise genetic distance threshold of 1.0%. 332 sequences of infected students aged≥18 years in Nanjing City, 1 904 sequences of non-student-infected individuals in Nanjing City and 1 698 non-Nanjing-infected individuals were obtained. Among the 332 infected students, the main route of infection was homosexual (96.39%), and the subtypes were CRF01_AE (37.95%), CRF07_BC (37.65%) and CRF105_0107 (10.24%). There were 890 sequences in the regional molecular transmission network, of which 21.80% were infected students in Nanjing City, 39.89% were non-student-infected individuals in Nanjing City, and 38.31% were non-Nanjing-infected individuals. In the CRF105_0107 transmission cluster, non-student-infected individuals from Nanjing accounted for 66.95% (81/121), while in the CRF07_BC transmission cluster, non-Nanjing-infected individuals accounted for 56.66% (200/353). There were 1 644 edges connected to infected students within the regional molecular transmission network, with local transmission accounting for 64.72% and regional transmission accounting for 35.28%. Regional transmission was mainly in Guangdong Province (19.83%) and other cities in Jiangsu Province (4.50%). The HIV-1 subtypes of newly reported HIV-infected students aged≥18 years in Nanjing City are mainly CRF01_AE, CRF07_BC and CRF105_0107, with local transmission as the main transmission characteristics. There is transmission between students and non-students.

Objective:To explore the applicability of modified comprehensive interventions in the treatment of non-severe dry eye syndrome in military pilots.Methods:A total of 88 military pilots with non-severe dry eye syndrome admitted to the Special Service Department of the 988th Hospital of the Joint Logistic Support Force between December 2021 and December 2023 were divided into an intervention group and a control group using the random number table method, with 44 cases in each. The intervention group received modified comprehensive interventions, while the control group underwent conventional treatment. The Ocular Surface Disease Index (OSDI), break-up time, tear meniscus height, changes in meibomian gland function, and levels of satisfaction of military pilots were compared between the 2 groups. The correlations between the OSDI, break-up time, tear meniscus height and levels of satisfaction were analyzed.Results:Before treatment, there was no significant difference in the OSDI between the 2 groups ( P>0.05). After 4 weeks of treatment, the changes in the OSDI of military pilots were smaller in the intervention group than in the control group ( t=3.21, P=0.002). After 2 and 4 weeks of treatment, the break-up time (both P<0.001) and tear meniscus height ( P<0.001, =0.012) of pilots in the intervention group exceeded those of the control group. In both groups, the break-up time (all P<0.001) and tear meniscus height (all P<0.001) kept increasing after treatment. After 4 weeks of treatment, there were significant differences in the distribution of meibomian gland function between the 2 groups ( Z=-2.55, -2.41, -2.29, P=0.011, 0.016, 0.022). Clinical care, procedure flow, and health education scored higher in the intervention group than in the control group during the survey on levels of satisfaction with the treatment ( t=6.55, 6.77, 3.63, all P≤0.001). The OSDI was negatively correlated with clinical care, procedure flow and health education ( r=-0.286, -0.275, -0.363, P=0.007, 0.010, 0.001) while the break-up time was positively correlated with clinical care and procedure flow ( r=0.248, 0.278, P=0.020, 0.009). Conclusions:The implementation of modified comprehensive intervention measures for dry eye syndrome in military pilots can effectively improve clinical symptoms and leave military pilots more satisfied.