Following repeated acupuncture treatments， some patients may develop a psychological dependence on the treatment behavior itself， referred to as "acupuncture dependence"， resulting from overactivation of the endogenous reward system and reinforcement of conditioned reflexes. This paper elucidates the clinical characteristics， neurobiological mechanisms， and psychological learning principles of this phenomenon， and differentiates it from somatic symptom disorder. The essence of acupuncture dependence is "treatment reward-driven overuse". Patients with personality disorders or somatization tendencies face a significantly higher risk of dependence due to deficits in emotion regulation. Clinical management should focus on three aspects including prevention， identification and intervention. Adopting tapering therapy and cognitive behavioral therapy can help patients restore rational medical-seeking behavior and avoid over-treatment.

OBJECTIVE: To provide a comprehensive summary of the technological evolution, clinical protocols, mechanisms of action, and current research progress of tibial transverse transport (TTT), with the goal of facilitating its standardized application in clinical practice. METHODS: A systematic review of both domestic and international literature on TTT for the treatment of diabetic foot was conducted. The analysis encompassed technical developments, surgical protocols, combination therapies, regenerative mechanisms, and clinical outcomes. RESULTS: Diabetic foot is one of the most severe complications of diabetes mellitus. Conventional treatments show limited efficacy in patients with advanced stages, such as Wagner grade 3/4 or Texas grade C and above. TTT, an evolution of the Ilizarov technique, promotes tissue regeneration through the "tension-stress principle". The procedure for the treatment of diabetic foot has evolved from an open large cortical window (120 mm×20 mm) to a minimally invasive small window (50 mm×15 mm), with incision length reduced to 10 mm and simplified external fixators. A dual-incision technique (10 mm apart) is now applied at 5 cm distal to the tibial tuberosity. Bone transport typically begins 3-5 days postoperatively at a rate of 1 mm/day, incorporating the "accordion technique" (2 weeks distraction+3 days stabilization+reverse transport). Multicenter studies report a limb salvage rate of 96.1%, wound healing rate of 96.3%, and amputation rate of less than 5%. Combining TTT with vascular reconstruction and antibiotic-loaded bone cement further enhances outcomes. There are also a series of studies on the mechanism of TTT in treating diabetic foot. TTT has been shown to activate the hypoxia-inducible factor 1α-vascular endothelial growth factor/stromal cell-derived factor 1 (HIF-1α-VEGF/SDF-1) signaling pathway to facilitate microcirculatory reconstruction; mobilize immune cells and rebalance macrophage polarization, thereby improving the inflammatory microenvironment; recruit stem cells via chemotaxis to accelerate re-epithelialization; and promote the release of regenerative small extracellular vesicles. CONCLUSION TTT demonstrates promising clinical potential in the treatment of diabetic foot, particularly in improving limb perfusion and promoting tissue repair. However, the underlying mechanisms have not been fully elucidated. Further in-depth investigations are required. In addition, the current lack of high-quality randomized controlled trials highlights the urgent need for rigorously designed randomized controlled trial to validate the efficacy and safety of this technique.
Humans ; Bone Transplantation/methods* ; Diabetic Foot/surgery* ; Ilizarov Technique ; Limb Salvage/methods* ; Tibia/surgery* ; Treatment Outcome

Neurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG. Both Nlrp6 knockout (Nlrp6^-/-) and NSC-conditional Nlrp6 knockout (Nlrp6CKO) mice were susceptible to stress, being more likely to develop depressive-like behaviors. Interestingly, NLRP6 was required for NSC proliferation in sustaining hippocampal neurogenesis and reinforcing stress resilience during growing up. Nlrp6 deficiency promoted esophageal cancer-related gene 4 (ECRG4) expression and caused mitochondrial dysfunction. Corticosterone as a stress factor significantly down-regulated NLRP6 expression, damaged mitochondrial function and suppressed cell proliferation in NSCs, which were blocked by Nlrp6 overexpression. ECRG4 knockdown reversed corticosterone-induced NSC mitochondrial function and cell proliferation disorders. Pioglitazone, a well-known clinical drug, up-regulated NLRP6 expression to inhibit ECRG4 expression in its protection against corticosterone-induced NSC mitochondrial dysfunction and proliferation restriction. In conclusion, this study demonstrates that NLRP6 is essential to maintain mitochondrial homeostasis and proliferation in NSCs, and identifies NLRP6 as a promising therapeutic target for hippocampal neurogenesis decline linked to depression.

The occurrence of eosinophilic leukemia complicated with cardiogenic embolism and L?ffler endocarditis are relatively rare.Early accurate diagnosis and prompt treatment can improve the its prognosis.When patients have symptoms of neurological impairment accompanied by increased eosinophils,the rare etiological type of cerebral infarction should be actively screened.Further improvements are needed in the examination of bone marrow smears,detection of fusion genes associated with leukemia,screening for L?ffler endocarditis,and identification of intraventricular thrombi.In this case,the main manifestations of eosinophilic leukemia were cardiogenic embolism and L?ffler endocarditis.After active treatment,the symptoms improved,and the eosinophil count returned to normal.This study summarizes the case data of this patient and combines it with a literature review,with the hope of raising clinicians'understanding of this rare disease.

Objective:To investigate the changes of intestinal microecology in the early stage of sepsis rat model by 16S rDNA sequencing.Methods:Sixty male Sprague-Dawley (SD) rats were randomly divided into cecal ligation and puncture (CLP) group and sham operation group (Sham group), with 30 rats in each group. In the CLP group, sepsis rat model was reproduced by CLP method; the rats in the Sham group only underwent laparotomy without CLP. At 24 hours after the operation, the intestinal feces and serum samples of 8 rats in each group were collected. The survival rate of the rest rats was observed until the 7th day. The level of serum tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Intestinal feces were sequenced by 16S rDNA sequencing technology. The operational taxonomic unit (OTU) data obtained after sequence comparison and clustering was used for α diversity and β diversity analysis, principal coordinate analysis and linear discriminant analysis effect size analysis (LEfSe) to observe the changes of intestinal microecology in early sepsis rats and excavate the marker flora.Results:At 24 hours after the reproduction of the model, the rats in the CLP group showed shortness of breath, scattered hair and other manifestations, and the level of serum TNF-α increased significantly as compared with that in the Sham group (ng/L: 43.95±9.05 vs. 11.08±3.27, P < 0.01). On the 7th day after modeling, the cumulative survival rate of the Sham group was 100%, while that of the CLP group was 31.82%. Diversity analysis showed that there was no significant difference in α diversity parameter between the Sham group and the CLP group (number of species: 520.00±52.15 vs. 492.25±86.61, Chao1 richness estimator: 707.25±65.69 vs. 668.93±96.50, Shannon index: 5.74±0.42 vs. 5.79±0.91, Simpson index: 0.93±0.03 vs. 0.94±0.05, all P > 0.05). However, the β diversity analysis showed that the difference between groups was greater than that within groups whether weighted according to OTU or not (abundance weighted matrix: R = 0.23, P = 0.04; abundance unweighted matrix: R = 0.32, P = 0.01). At the phylum level, the abundance of Proteobacteria and Candidatus_sacchari in the CLP group increased significantly as compared with the Sham group [18.100% (15.271%, 26.665%) vs. 6.974% (2.854%, 9.764%), 0.125% (0.027%, 0.159%)% vs. 0.018% (0.008%, 0.021%), both P < 0.05]. At the genus level, the abundance of opportunistic pathogen including Helicobacter, Ruthenium, Streptococcus, Clostridium ⅩⅧ in the CLP group was significantly higher than that in the Sham group [5.090% (1.812%, 6.598%) vs. 0.083% (0.034%, 0.198%), 0.244% (0.116%, 0.330%) vs. 0.016% (0.008%, 0.029%), 0.006% (0.003%, 0.010%) vs. 0.001% (0%, 0.003%), 0.094% (0.035%, 0.430%) vs. 0.007% (0.003%, 0.030%), all P < 0.05], and the abundance of probiotics such as Alloprevotella and Romboustia was significantly lower than that in the Sham group [7.345% (3.662%, 11.546%) vs. 22.504% (14.403%, 26.928%), 0.113% (0.047%, 0.196%) vs. 1.229% (0.809%, 2.29%), both P < 0.01]. LEfSe analysis showed that the probiotics belonging to Firmicutes were significantly enriched in the Sham group, and Romboustia was the most significantly enriched species. Opportunistic pathogens such as Helicobacter, Streptococcus and Clostridium ⅩⅧ were significantly enriched in the CLP group, Helicobacter_NGSU_ 2015 was the most significantly enriched species. Conclusion:In the early stage of sepsis, the intestinal microbiota structure of rats is significantly changed, which mainly shows that the abundance of Alloprevotella and other probiotics is significantly reduced, while that of Helicobacter and other opportunistic pathogens is significantly increased.

[Objective]To analyze the prognostic factors of resectable acral melanoma patients ,then develop a novel prognostic model and examined its prognostic value.[Methods]The study retrospectively analyzed clinicopathological characteristics and inflam?matory markers of 232 acral melanoma patients who underwent radical surgical resection between 2000 and 2011 at the Sun Yat-sen University Cancer Center. Kaplan-Meier curves were plotted to estimate overall survival. Significantly predictive factors were identified by multivariate Cox regression analyses and a prognostic model based on these variables was constructed to predict survival.[Results]Cox regression analysis revealed that age,lactic dehydrogenase(LDH),stage,globulin(GLB)and C-reactive protein (CRP)were independently related to survival. After computing these scores ,patients were classified into three risk groups. The new prognostic model identified three categories of patients with different prognoses(P<0.001)and significantly stratify patient prognosis in different tumor stages. The 5-year survival rate was 42.9%,25.7%,and 3.7%in groups 1,2,and 3,respectively. The AUC of new prognostic model is 0.664(95%CI:0.599-0.724).[Conclusion]Age,LDH,stage,GLB and CRP were independently related to survival in our study population,and the prognostic model is useful to stratify patients into different risk groups and it is a useful complement to AJCC staging for Asian patients with acral melanoma.

Objective:To examine the oncogenic mutations involved in melanoma in Southern China and to provide a theoretical basis for the development of melanoma molecular targeted therapy strategy. Methods:The Sequenom platform (OncoCarta Panel v1.0 and MassARRAY System) was used to determine the prevalence of oncogene mutations in 28 acral melanoma samples, 28 mucosal mel-anoma samples, and 30 non-chronic sun-induced-damage (no-CSD) melanoma samples from Southern China. Results:At least one mu-tation was detected in 33 of the 86 melanomas (38.4%) with mutations observed in BRAF (16.3%), NRAS (10.5%), KIT (5.8%), EGFR (4.7%), HRAS (2.3%), KRAS (2.3%), MET (2.3%), and PIK3CA (1.2%). In BRAF, the age of patients with mutations was significantly lower than those without BRAF mutation (45.7±15.3 vs. 55.9±12.7, P=0.01). Patients with mutations in NRAS were more likely to have ulceration compared with patients without NRAS mutations (88.9%vs. 48.1%, P=0.049). Conclusions:This study represents a compre-hensive and concurrent analysis of the major recurrent oncogenic mutations involved in melanoma cases from Southern China areas. The data have implications for both clinical trial designs and therapeutic strategies.

Objective: To observe the tolerability of Chinese melanoma patients to four-week high-dose interferon alfa-2b(INTRON A(R)，Schering-Plough)therapy. Methods:A total of 29 patients with high risk melanoma[American Joint Committee on Cancer Staging(AJCC)ⅡB-ⅢC]who received adjuvant interferon therapy in our hospital between September 2007 and May 2009 were retrospectively reviewed.Patients received 4 hours of intravenous infusion of interferon alfa-2b fdose range，22.00 million international unit(MIU)to 33.75 MIU]Ⅳ 5 days/week for 4 weeks.The adverse events were evaluated with National Cancer Institute Common Toxicity Criteria(NCI 2.0 version). Results: The average daily dose was 17.63 MIU/(m~2·d).The therapy was ended in two patients because of poor wound healing or intolerability to severe fatigue.The most common adverse events were myelosuppression.Grade 3/4 neutropenia was observed in 69% (20/29)patients and was rapidly reversed after conventional support interventions.Grade 1/2 abnormal hepatic function occurred in 18 cases(62%).Twenty-six patients were followed up for 3 to 22 months.Five patients developed early progression:one with local recurrence，two with regional lymph node metastasis one with in-transit metastasis in the affected limb,and one with distant metastasis. Conclusion: High-dose interferon alfa-2b regimen can be well tolerated by Chinese patients but cannot effectively inhibit subclinical lesions.

AIM: Recombinant human adenovirus-p53 injection (rAd-p53) is the first marketed gene therapeutic drug worldwide. This study aimed to evaluate the safety and primary efficacy of rAd-p53 administrated on advanced solid tumors. METHODS: 24 patients with advanced solid tumor treated with rAd-p53 were reviewed, including 5 cases of renal carcinoma, 4 of nasopharyngeal carcinoma, 4 of colorectal carcinoma, 2 of melanoma, 1 of non-small-celllung cancer, 1 of esophageal carcinoma, 1 of gastric cardia carcinoma, 1 of thymic carcinoma, 1 of duodenal carcinoma, 1 of thyroid carcinoma, 1 of pancreatic carcinoma, 1 of endometrial carcinoma and 1 of rhabdomyosarcoma. RAd-p53 was weekly administrated at the dose of 1?10~ 12 VP, and 4 times of administration was defined as one cycle. Administration approach included intratumoral injection,intrabronchial drop in, intraperitoneal injection, intra-arterial infusion and intravenous drip. Combined therapy was given with chemotherapy in 18 cases, radiotherapy in 2, concomitant chemotherapy and radiotherapy in 1, abdominal thermotherapy and orally gefitinib in 1, cytokine immunotherapy in 1 and without combination therapy in 1. RESULTS: 23 cases underwent 35 cycles of therapy except for 1 case discontinued because of early progression. Among the 21 evaluable cases 5 PR, 5 SD and 11 PD were observed. Overall response rate was 23.8%(5/21) and disease control rate was 47.6%(10/21). Grade I-II injection site pain, chill, fever and myalgia were the most frequent side effects. Grade III fever developed in 2 cases and grade III-IV myelosuppression in 4 cases combined with chemotherapy. Furthermore, severe ostealgia occurred in 2 cases and transient hypotension in 1. CONCLUSION: RAd-p53 is tolerable in patients with advanced solid tumor. A further randomized clinical trial is necessary to confirm the antitumor activity of rAd-p53 combined with conventional strategies.