Syndrome differentiation and treatment is an integral part of the traditional Chinese medicine （TCM） diagnostic and therapeutic system， whose development exhibits distinct stages. This paper systematically reviews the evolutionary trajectory of syndrome differentiation and treatment， from symptom-based treatment in Inner Canon of Yellow Emperor （《黄帝内经》）， to ZHANG Zhongjing's establishment of the disease-pulse-syndrome-treatment framework， through its application and development in the Ming and Qing dynasties， and finally to its recognition as a fundamental characteristic of TCM in modern times. However， the overemphasis on syndrome differentiation and treatment， coupled with a diminished focus on disease concepts， has led to its gradual alienation as the primary diagnostic and therapeutic model. The alienation mainly manifests as a tendency to prioritize syndrome over disease， resulting in the overgeneralization and limited application of the concept， and causing a lack of specificity in practice. This paper emphasizes that a correct understanding of syndrome differentiation and treatment is a necessary premise for the deve-lopment and improvement of the TCM diagnostic and therapeutic system. By integrating modern medical diagnosis to clarify disease targets and applying TCM thinking to extract common patterns of diseases， precise alignment between syndrome differentiation and treatment and modern clinical demands can be achieved， providing a reference for addressing the contemporary challenges of syndrome differentiation and treatment.

It is the current confusion encountered by integrated Chinese and Western medicine that how to find the breakthrough direction of integrating Chinese and Western medicine， from crossover to integration to innovation， and open up a new horizon of integrated Chinese and Western medicine. The progress of Chinese medicine lay in expanding the scope of diagnosis and treatment with the help of modern diagnostic and therapeutic equipments and developing “micro” identification， while the progress of Western medicine lay in looking at “macro” and developing systemic medicine and integrated medicine， both of which are in the direction of each other. The “state-target identification and treatment” may become an important way to build a modern diagnosis and treatment system of integrated Chinese and Western medicine， and the thinking mode of “from target to state” is a further refinement and development on the basis of the theoretical system of “state-target identification and treatment”， which provided a clearer solution for the current stage of the integrated Chinese and Western medicine model， and pointed out the important development direction for the future integrated Chinese and Western medicine. From the perspective of strategic level and diagnosis and treatment practice， it integrated the “target-state” thinking mode into the modern diagnosis and treatment model of the integrated Chinese and Western medicine， i.e.， “Western medicine as the basis and treating with Chinese medicine； Chinese medicine as the basis and treating with Western medicine”. On the one hand， Western medicine should strengthen the reference to the traditional theories and holism of Chinese medicine， and advocate a higher level of education on the integrated Chinese and Western medicine under the guidance of the traditional theories of Chinese medicine. On the other hand， the “from target to state” mode of thinking should be applied to guide the establishment of diagnostic and treatment strategies and clinical selection of medicines in clinical practice， so as to locate the target and adjust the body state in a gradual and orderly manner， and to provide practical methods for the modern clinical work of the integrated Chinese and Western medicines. Chinese and Western medicine systems can learn from each other， combine organically， give full play to their respective strengths， and form an internal law， so as to make breakthroughs and innovations in the integrated Chinese and Western medicine model.

Objective:To explore the diagnosis and treatment of enterovesical fistula.Methods:The clinical data of 12 patients with enterovesical fistula at the First Affiliated Hospital of Soochow University from Jan 2012 to Dec 2021 were retrospectively analyzed.Results:There were 5 cases of rectovesical fistula, 4 cases of sigmoid colovesical fistula, 1 case of cecovesical fistula, and 2 cases of ileovesical fistula , with 1 female patient having concurrent vaginal vesical fistula . CT was carried out in 6 cases, enteroscopy in 5 cases, cystoscopy in 6 cases, cystography in 3 cases, and enterography in 2 cases. Eleven cases underwent surgical treatment, 1 case did not. Five cases underwent more than two operations, 1 case still had enterovesical fistula and died after ileostomy, 2 cases improved after enterotomy. One case underwent bowel resection and bladder repair and 3 cases underwent bowel resection and anastomosis combined with partial or total cystectomy, 4 cases underwent bowel resection, bladder repair, transverse colon or ileostomy. One died, 1 case still had enterovesical fistula and 10 cases were cured. There were no recurrence on follow-up.Conclusions:Enterovesical fistula is often secondary to intestinal tumors, and its clinical manifestations are mostly fecaluria and urinary tract infections. CT, cystoscopy, cystography and enterography are important diagnostic methods. Surgical treatment is the choice of therapy.

Objective:To explore the necessity of salvage surgery after endoscopic resection of early rectal cancer.Methods:The clinical data of 62 patients who underwent salvage surgery for early rectal cancer at the First Affiliated Hospital of Soochow University from Jan 2012 to Dec 2021 were retrospectively analyzed.Results:Six cases (10%) had residual tumors, 8 cases (13%) had lymph node metastasis and one case (2%) had cancer nodules; The operation time was (178±82) mins; 1 case (2%) developed anastomotic lerakage, which was cured; 2 cases (3%) developed intestinal obstruction, of which 1 case (2%) relieved on conservative management and 1 case (2%) underwent reoperation.Conclusion:It is necessary to perform salvage surgery for early rectal cancer patients with residual caner and risk factors of lymph node metastasis after endoscopic therapy.

Various new ophthalmic formulations have been prepared to enhance ocular bioavailability,while lots of irritant sub-stances are applied,including surfactants,polymers and other cationic materials. Therefore,safety of the preparations has been paid more and more attention besides the efficacy. Since in vitro experiments lack of associated enzymes and integral reaction of organiza-tion,the reasonability and correlation of the results extrapolated to the animal experiments still need to be further proved. The in vivo common eye irritation methods( winking,histopathological slices,Draize score and confocal microscopy test etc)were reviewed,eval-uated and analyzed in the paper.

OBJECTIVETo investigate the role of sphingosine kinase 1 (SphK1) in regulating the proliferation of hypoxia-exposed glioma cells in vitro and explore the possible molecular mechanisms.

METHODSHuman glioblastoma U87MG cells was transfected with specific small interfering RNA (siRNA) constructs targeting SphK1, and the efficiency of SphK1 knockdown was validated by real-time PCR and Western blotting. The cells transfected with SphK1 siRNA and with a negative control siRNA were then exposed to 3% oxygen or 150 µmol/L CoCl2 to induce hypoxia. The cell proliferation and cell cycle changes following the exposure were evaluated with the Cell Counting Kit-8 and flow cytometry, respectively, and the intracellular Ca(2+) changes were monitored using Flou-4/AM under an inverted laser scanning confocal microscope.

RESULTSSphK1 knockdown significantly reduced hypoxia-induced calcium reflux and suppressed the cell proliferation. Application of OAG, an activator of calcium channels, however, obviously enhanced the cell proliferation under hypoxia.

CONCLUSIONSphK1 promotes the proliferation of glioma cells under hypoxia via regulating calcium signaling.

Calcium Signaling ; Cell Cycle ; Cell Hypoxia ; Cell Line, Tumor ; Cell Proliferation ; Glioblastoma ; Glioma ; pathology ; Humans ; Phosphotransferases (Alcohol Group Acceptor) ; metabolism ; RNA, Small Interfering

Objective:To review the application of microemulsions as vehicles in transdermal delivery systems. Methods:Based on the recently published papers, the research on the application of microemulsions was classified and summarized. Results: Microe-mulsions is extensively applied as drug vehicles due to the ability of solubilization, drug permeation enhancement and efficacy improve-ment. Conclusion:Microemulsions as promising vehicles for transdermal delivery show a good application prospect.

Objective:To review the progress in vaginal mucoadhesive drug delivery systems. Methods:Based on the recently published papers,the research on the application of vaginal mucoadhesive drug delivery systems was classified and summarized. Re-sults:Vaginal mucoadhesive drug delivery systems not only showed safety,effectiveness and strong permeability but also avoided the first pass effect,prolonged drug residence time and improved bioavailability and compliance of patients. Conclusion:Vaginal mucoad-hesive drug delivery systems are becoming research hotspots and exhibit broad application prospects to replace the traditional delivery systems.

The stratum corneum barrier and the other issues in transdermal drug delivery system have attracted more and more at-tention, and the novel liposomes as the drug delivery vehicles effectively solve the problems. The novel liposomes can significantly im-prove transdermal drug penetration, therefore, can enhance efficacy and shows high application value and development prospects. In the paper, combined with some domestic and foreign current researches, the classification, penetration mechanisms and application of the novel liposomes were reviewed.

Objective To investigate the role of sphingosine kinase 1 (SphK1) in regulating the proliferation of hypoxia-exposed glioma cells in vitro and explore the possible molecular mechanisms. Methods Human glioblastoma U87MG cells was transfected with specific small interfering RNA (siRNA) constructs targeting SphK1, and the efficiency of SphK1 knockdown was validated by real-time PCR and Western blotting. The cells transfected with SphK1 siRNA and with a negative control siRNA were then exposed to 3%oxygen or 150μmol/L CoCl2 to induce hypoxia. The cell proliferation and cell cycle changes following the exposure were evaluated with the Cell Counting Kit-8 and flow cytometry, respectively, and the intracellular Ca2+changes were monitored using Flou-4/AM under an inverted laser scanning confocal microscope. Results SphK1 knockdown significantly reduced hypoxia-induced calcium reflux and suppressed the cell proliferation. Application of OAG, an activator of calcium channels, however, obviously enhanced the cell proliferation under hypoxia. Conclusion SphK1 promotes the proliferation of glioma cells under hypoxia via regulating calcium signaling.