ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

ObjectiveTo explore the characteristics of traditional Chinese medicine （TCM） syndromes in the patients with concurrent knee osteoarthritis （KOA） and postmenopausal osteoporosis （PMOP） and provide a scientific basis for precise TCM syndrome differentiation， diagnosis， and treatment of such concurrent diseases. MethodsA prospective， multicenter， cross-sectional clinical survey was conducted to analyze the characteristics of TCM syndromes in the patients with concurrent PMOP and KOA. Excel 2021 was used to statistically analyze the general characteristics of the included patients. Continuous variables were reported as x¯±s， and binary variables were reported as percentages. UCINET and Gephi were used to construct a complex "isease-syndrome-symptom" network for in-depth mining. Topological structure indicators， edge connection information between nodes， and weighted adjacency matrices were calculated by UCINET and Python. Gephi was used for complex network visualization. ResultsA total of 157 patients with concurrent PMOP and KOA from 12 TCM hospitals or community health service centers were selected for the collection of TCM syndrome and symptom information. A total of 4 main TCM syndromes were obtained， which were kidney-Yang deficiency （47.13%）， liver-kidney Yin deficiency （36.94%）， spleen-kidney Yang deficiency （8.92%）， and kidney Yin-Yang deficiency （7.01%）. In addition， 10 concurrent syndromes （mainly Qi stagnation and blood stasis， Qi and blood deficiency， spleen Yang deficiency， and cold-dampness） were identified. Based on the results of comprehensive frequency statistics and complex network analysis， as well as TCM theoretical knowledge and relevant guidelines， the general characteristics of concurrent PMOP and KOA and the main TCM syndromes in the dimensions of physical symptoms， pain， tongue and pulse manifestations， and defecation and urination were obtained. ConclusionThe main TCM syndromes in the patients with concurrent PMOP and KOA may be kidney Yang deficiency， liver-kidney Yin deficiency， spleen-kidney Yang deficiency， and kidney Yin-Yang deficiency， among which kidney Yang deficiency and liver-kidney Yin deficiency are the core TCM syndromes.

Pancreatic cancers (PCs) is a common malignant tumor with poor prognosis in the digestive system. Its main treatment methods include surgery, radiotherapy, chemotherapy, and targeted therapy. The early diagnosis rate of hidden onset of PCs is low, and most patients have already lost the opportunity to undergo surgery when diagnosed with PCs. Chemotherapy is still the main treatment for advanced PCs, but the use of chemotherapy drugs in PCs can easily lead to drug resistance. The most significant feature that distinguishes PCs from other tumors is its rich and dense matrix, which not only hinders drug penetration but also impedes the infiltration of immune cells. The above reasons have led to a very low survival rate of PCs patients. Therefore, drug delivery systems are very important in the diagnosis and treatment of PCs. They can improve drug delivery, enhance biological barrier penetration, reduce side effects, and combine multiple treatment methods. Therefore, the treatment prospects of PCs are very broad. Currently, drug delivery systems widely applied in PCs primarily include nanodrug delivery systems, tumor microenvironment-targeted drug delivery system, immunotherapy drug delivery system, gene therapy drug delivery system, and combination therapy drug delivery system that synergize multiple therapeutic modalities. Emerging drug delivery systems (DDSs) have revolutionized PCs treatment by addressing these challenges through multiple mechanisms. Nanoformulations improve drug solubility, prolong circulation time, and reduce systemic toxicity via passive/active targeting. Smart DDSs responsive to PCs-specific stimuli enable extracellular matrix degradation, tumor-associated fibroblasts reprogramming, and vascular normalization to enhance drug accessibility. Last but not least, carrier systems loaded with myeloid-derived suppressor cell inhibitors or T cell activators can reverse immunosuppression and potentiate immunotherapy efficacy. Advanced platforms co-deliver chemotherapeutics with immunomodulators, gene-editing tools, or sonodynamic agents to achieve synergistic antitumor effects. These platforms aim to address critical challenges in PCs treatment, such as enhancing drug bioavailability, overcoming stromal barriers, reprogramming immunosuppressive niches, and achieving multi-mechanistic antitumor effects. This article provides a systematic summary and prospective analysis of the current development status, latest cutting-edge advances, opportunities, and challenges of the above-mentioned drug delivery systems in the field of PCs therapy.

Background::Although the treatment of peripheral T-cell lymphoma (PTCL) has undergone advancements during the past several years, the response rate and long-term effects with respect to patients with PTCL remain unsatisfactory—particularly for relapsed or refractory (R/R) patients. This phase II trial was designed to explore the efficacy and safety of an all-oral regimen of chidamide plus prednisone, cyclophosphamide, and thalidomide (CPCT) for R/R PTCL patients who could not tolerate the standard chemotherapy for a variety of reasons.Methods::We conducted a multicenter phase II clinical trial in which we combined chidamide (30 mg twice weekly) with prednisone (20 mg daily after breakfast), cyclophosphamide (50 mg daily after lunch), and thalidomide (100 mg daily at bedtime) (the CPCT regimen) for a total of fewer than 12 cycles as an induction-combined treatment period, and then applied chidamide as single-drug maintenance. Forty-five patients were ultimately enrolled from August 2016 to April 2021 with respect to Chinese patients at nine centers. Our primary objective was to assess the overall response rate (ORR) after the treatment with CPCT.Results::Of the 45 enrolled patients, the optimal ORR and complete response (CR)/CR unconfirmed (CRu) were 71.1% (32/45) and 28.9% (13/45), respectively, and after a median follow-up period of 56 months, the median progression-free survival (PFS) and overall survival (OS) were 8.5 months and 17.2 months, respectively. The five-year PFS and OS rates were 21.2% (95% confidence interval [CI], 7.9-34.5%) and 43.8% (95% CI, 28.3-59.3%), respectively. The most common adverse event was neutropenia (20/45, 44.4%), but we observed no treatment-related death.Conclusion::The all-oral CPCT regimen was an effective and safe regimen for R/R PTCL patients who could not tolerate standard chemotherapy for various reasons.Trial Registration::ClinicalTrials.gov, NCT02879526.

Objective:To investigate the clinical effect of the modified vertical rectus abdominis myocutaneous flap in repairing the skin and soft tissue defect after abdominoperineal resection for rectal cancer.Methods:This study was a retrospective observational study. From June 2019 to July 2022, five male patients with low rectal cancer who were conformed to the inclusion criteria were admitted to the Department of Basic Surgery of Xiangya Hospital of Central South University, with ages ranging from 65 to 70 years and the sizes of the perianal skin ulcers ranging from 5 cm×4 cm to 11 cm×9 cm, and all of them underwent abdominoperineal resection. The secondary skin and soft tissue defects in the perineum with an area of 8 cm×6 cm-14 cm×12 cm (with the depth of pelvic floor dead space being 10-15 cm) were repaired intraoperatively with transplantation of modified vertical rectus abdominis myocutaneous flaps with the skin area being 9 cm×7 cm-16 cm×12 cm, the volume of the muscle being 18 cm×10 cm×5 cm-20 cm×12 cm×5 cm, and the vessel pedicle being 18-20 cm in length. During the operation, most of the anterior sheath of the rectus abdominis muscle was retained, the flap was transferred to the recipient area through the abdominal cavity, the remaining anterior sheaths of the rectus abdominis muscle on both sides of the donor area were repeatedly folded and sutured, the free edge of the transverse fascia of the abdomen was sutured with the anterior sheath of the rectus abdominis muscle, and the donor area skin was directly sutured. After the operation, the survival of the transplanted myocutaneous flap was observed. The occurrence of complications in the perineal recipient area was recorded within 2 weeks after the operation. The recovery of the perineal recipient area and the abdominal donor area was observed during follow-up, and the occurrence of complications in the donor area of the abdomen as well as the recurrence of tumors and metastasis were recorded.Results:All transplanted myocutaneous flaps in 5 patients survived after surgery. One patient had dehiscence of the incision in the perineal recipient area 2 days after surgery, which healed after 7 d with intermittent dressing changes and routine vacuum sealing drainage treatment. In the other 4 patients, no complications such as incisional rupture, incisional infection, or fat liquefaction occurred in the perineal recipient area within 2 weeks after surgery. Follow-up for 6-12 months after discharge showed that the skin of the perineal recipient area had good color, texture, and elasticity, and was not bloated in appearance; linear scars were left in the perineal recipient area and the abdominal donor area without obvious scar hyperplasia or hyperpigmentation; no complications such as incisional rupture, incisional infection, intestinal adhesion, intestinal obstruction, or weakening of the abdominal wall strength occurred in the abdominal donor area, and the abdominal appearance was good with no localized bulge or formation of abdominal hernia; there was no local recurrence of tumor or metastasis in any patient.Conclusions:The surgical approach of using the modified vertical rectus abdominis myocutaneous flap to repair the skin and soft tissue defects after abdominoperineal resection for rectal cancer is relatively simple in operation, can achieve good postoperative appearances of the donor and recipient areas with few complications, and is worthy of clinical promotion.

Objective To investigate the value of deep learning(DL)model based on integrated 18F-FDG PET/MRI for evaluating cerebral metabolic status around cerebral infarction.Methods A total of 46 patients with cerebral infarction caused by unilateral internal carotid artery(ICA)or middle cerebral artery(MCA)steno-occlusion were retrospectively collected.Based on integrated 18F-FDG PET/MRI,DL model was used to automatically segment cerebral infarction area.Asymmetry index(AI)was used to evaluate the volume of reduced metabolic areas in the segmented affected frontal lobe,temporal lobe,parietal lobe,occipital lobe and cerebral hemisphere of cerebral infarction area as well as their proportions,while their correlations with National Institutes of Health stroke scale(NIHSS)score of neurological function were analyzed.Results Among 46 patients,the volume of decreased metabolism in the affected temporal lobe,parietal lobe and cerebral hemisphere was(41.35±10.52)ml,(65.58±14.82)ml and(178.89±34.23)ml,respectively,all positively correlated with NIHSS scores(rs=0.359,0.343,0.362,all P＜0.05).The proportion of the reduced metabolic volume in the affected frontal lobe,temporal lobe,parietal lobe and cerebral hemisphere was(45.68±10.35)%,(42.32±10.19)%,(45.05±9.44)%and(44.11±8.63)%,respectively,all positively correlated with NIHSS scores(rs=0.344,0.340,0.439,0.393,all P＜0.05).Conclusion DL model based on integrated 18F-FDG PET/MRI was of important clinical value for evaluating cerebral metabolic state around cerebral infarction.

Objective To explore the preventive and therapeutic effects of Caryopteris incana decoction in a rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome.Methods Sixty healthy specific pathogen-free SD female rats were randomly divided into six groups of ten rats each:normal group,model group,ibuprofen group,C.incana high-dose group,C.incana medium-dose group,and C.incana low-dose group.All groups except the normal group were treated with cold stimulation combined with estradiol benzoate and oxytocin to establish a rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome.On the fifth day of modeling,the rats were intragastrically administered the study drugs for 10 days.Their symptoms were observed and recorded.The writhing response and hemorheological indices were measured.The serum levels of TXB2,6-keto-prostaglandin F1α(6-Keto-PGF1α),estradiol(E2),and progesterone(PROG)were measured.Additionally,the levels of prostaglandin F2α(PGF2α),prostaglandin E2(PGE2),nitric oxide(NO),and calcium(Ca2+)in the uterine tissues were measured.The organ indices of the uterus and ovary were calculated,and histopathological changes were observed.Results Compared with the normal group,the rats in the model group showed obvious symptoms of cold coagulation and blood stasis syndrome and writhing reaction.The morphology of uterus and ovary showed obvious hyperplasia,inflammation,edema and other lesions.The plasma viscosity,packed cell volume and whole blood viscosity were significantly increased(P＜0.01).The serum levels of thromboxane B2 and E2 and the E2/PROG ratio were significantly increased(P＜0.01),the levels of 6-Keto-PGF1α and PROG were significantly decreased(P＜0.01).The uterine index and ovarian index were significantly increased(P＜0.01).The levels of PGF2α and Ca2+and the PGF2α/PGE2 ratio in uterine tissue were significantly increased(P＜0.01),while the levels of PGE2 and NO were significantly decreased(P＜0.01).Compared with the model group,Caryopteris incana significantly improved the symptoms of model rats,improved the morphological lesions of the uterus and ovary,prolonged the latency time of the writhing reaction,and reduced the number of writhing episodes(P＜0.01);significantly reduced the plasma viscosity,packed cell volume,and whole blood viscosity(P＜0.01);significantly reduced the serum levels of TXB2 and E2 and the E2/PROG ratio,increased the serum levels of 6-Keto-PGF1αand PROG,and reduced the uterine and ovarian indices(P＜0.01,P＜0.05);significantly reduced the levels of PGF2αand Ca2+and the PGF2α/PGE2 ratio in uterine tissue(P＜0.01,P＜0.05);and significantly increased the levels of PGE2 and NO in the uterine tissue(P＜0.01).Conclusions Caryopteris incana decoction can effectively improve the clinical symptoms of primary dysmenorrhea in rats with cold coagulation and blood stasis syndrome,and it has a good control effect.Its mechanism may be correlated with the levels of TXB2,6-Keto-PGF1α,E2,and PROG in serum and PGF2α,PGE2,NO,and Ca2+in uterine tissue.

Objective To study the effects and mechanism of norcantharidin(NCTD)on proliferation and apoptosis of NB4 and K562 human leukemic cells by regulating phosphoprotein phosphatase 5 catalytic(PPP5C).Methods PC3.1 and PPP5C-PC3.1 plasmids were electroporated into NB4 and K562 cells.Stable NB4 and K562 cell lines were selected with geneticin(G418).Protein and mRNA expression levels of PPP5C were measured by Western blot and RT-qPCR,respectively.Proliferation,migration,and apoptosis of NB4 and K562 cells were determined by a CCK-8 assay,transwell assay,and Live & Dead? animal cell viability/toxicity detection kit,respectively.NB4 and K562 cells were divided into 0 μg/mL NCTD group and various NCTD dose groups,and cultured in RPMI 1640 medium containing 0,8,16,or 32 μg/ml NCTD.The Live & Dead? animal cell viability/toxicity detection kit measured the numbers of dead and live cells,and cell morphology was observed under a microscope.Western blot was used to measure protein expression levels of caspase 3,Cleaved caspase 3,JNK,p-JNK,p38,p-p38,and α-Tubulin.Results Proliferation,migration,and apoptosis of NB4 and K562 cells were enhanced by overexpression of PPP5C.Compared with 0 μg/mL NCTD group,NCTD promoted apoptosis in a dose-dependent manner.PPP5C overexpression antagonized the killing effect of NCTD on leukemic cells.Mechanistic investigations showed that PPP5C reduced the protein level of p-JNK by dephosphorylating and regulating the expression of apoptosis-related protein Cleaved caspase 3.Conclusions NCTD promotes apoptosis of NB4 and K562 cells and inhibits their proliferation by inhibiting PPP5C.

Nipah virus(NipahVirus,NiV)is a zoonotic virus that can cause encephalitis and severe respiratory symptoms in humans and animals,and is at risk of being introduced into China.At present,there are many factors related to the transmission of Nipah virus disease(NVD),but the actual effects of these factors are controversial.Therefore,with the help of meta-analysis,this paper aims to determine the current mortality and the main means of transmission of NVD,so as to pro-vide reference for the input of controlling Nipah virus disease and making emergency plans for pre-vention and control in our country.By searching the articles published in Pubmed,Embase,Web of knowledge,CNKI,VIP Chinese Sci-tech Journals Database and Wanfang Database up to December 31,2022,the literature of cross-sectional,cohort and case-control studies with NiV encephalitis fa-tality rate(CFR)and risk factors were selected.Results showed that a total of 25 literatures were included in the meta-analysis after retrieval and screening,and the fatality rate of NiV encephalitis was 64.6％(95％CI,60.8-68.2;I2=96.8％).Subgroup analysis showed that tree climbing(OR=1.43;95％CI:1.05-1.96),bats were seen near their nighttime residence(OR=2.38;95％CI:1.74-3.25)and direct contact with date palm SAP(OR=6.01;95％CI:4.07-8.89)Bananas(OR=2.25;95％CI:1.31-3.85)OR porcine(OR=11.87;95％CI:1.15-122.23)was significantly associated with NiV encephalitis.The results of this study suggest that NiV encephalitis has a high mortality rate,and tree climbing,nocturnal exposure to bats,and exposure to pig,banana,and date palm SAP increase the risk of NiV encephalitis.In order to prevent NiV transmission,epidemic surveillance,education and publicity should be strengthened and protective measures should be taken.

Using the"structure-process-outcome-institution"framework,this article analyzes the conceptual connotation and manifestation of primary care resilience.The mechanism by which digital technologies embedding improve organizational resilience of primary healthcare institution was elucidated;From the resilience perspective,an action framework for reshaping the primary healthcare system by digital technologies was constructed.Research has found that:1)Organizational resilience is the core of primary healthcare resilience.2)Digital technologies mainly promote coupling coordination between resource and organization through promoting change perception,knowledge absorption,and knowledge integration,improve organizational resilience of primary healthcare institution.3)There is a bidirectional interaction between the improvement of organizational resilience and reshaping primary healthcare system;4)The relevant departments should unify instrumental rationality,institutional rationality,and value rationality to establish the embedding,governance,and evaluation framework for digital technologies to reshape the primary healthcare system.