Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo establish an adjusted Serfling regression model to estimate the excess cases and the excess epidemic period of hand-foot-mouth disease (HFMD) in Beijing from 2011 to 2019, so as to provide data support and decision-making basis for HFMD prevention and control. MethodsThe weekly number of HFMD cases in Beijing from 2011 to 2019 was utilized for adjusted the Serfling regression model. Then the adjusted model was used to fit the baseline and epidemic threshold of HFMD in Beijing from 2011 to 2019, calculating the excess cases and determining the excess epidemic period. ResultsA total of 279 306 cases of HFMD were reported in Beijing from 2011 to 2019, with the climax of the disease occurring in summer and autumn. After adjusting the fitting R² of the Serfling regression model to 0.773, a total of 10 excess epidemic periods totaling 92 weeks were estimated, mainly occurring in summer. The highest number of excess cases during an excess epidemic period was found in 2014 (1 272 cases, 95%CI: 990‒1 554), accounting for 65.04% of the actual cases (95%CI: 50.62%‒79.46%). ConclusionThe adjusted Serfling regression model fits well and can be utilized for early warning of HFMD and estimating the disease burden caused by HFMD.

Objective To investigate the reproductive and developmental effects of Clothianidin in rats. Methods Clothianidin was administrated by diet to both parental and first filial (F 1) generations of rats at the dosages of 0, 30.51, 110.84 and 304.26 mg/(kg·d) in females, and 0, 26.45, 92.69 and 279.42 mg/(kg·d) in males. Clothianidin was administered through diet to male and female rats for 8 weeks before mating. Clothianidin was administered to female rats in the parental and F1 generations during mating, gestation and lactation periods. During the test, toxicity performance was observed, reproduction index was calculated, and pathological examination was carried out. Results The body weights of rats in the parent and F1 generations in the high-dose group were lower than those in the control group during pre-mating exposure and at various time points during pregnancy and lactation (P<0.05). The pregnancy rates of parental and F1 generations in the high-dose group were lower than those of the control group (48.57% vs 71.43%, 45.71% vs 80.00%, P＜0. 05). Sperm concentration and sperm motility of the parental generation were lower than those of the control group [(42.55±12.87) vs (53.84±7.65) ×106/ml, (58.94±10.59) vs (65.59±6.03), （P＜0.05）]. Sperm concentration and sperm motility of the F1 generation were lower than those of the control group [(41.64±12.42) vs (53.09±9.48), (55.13±9.19) vs (64.53±6.31), (P＜0.05). Conclusion Exposure to clothianidin has reproductive toxicity to Wistar rats, and the no-observed adverse effect level (NOAEL) in the two-generation reproductive toxicity test is 92.69 mg/kg·BW for males and 110.84 mg/kg·BW for females in Wistar rats.

As a common medical condition， vertigo can be induced by multiple diseases in the modern medical system. Its incidence rate shows an upward trend with the increase in age. According to the theory of mutual interference between clear Qi and turbid Qi in Huangdi's Internal Classic （Huang Di Nei Jing）， this paper systematically analyzes the pathogenesis of vertigo and explores the mechanism and clinical application value of Xiao Chaihutang in the treatment of vertigo. It is believed that the mutual inference between clear Qi and turbid Qi leads to the failure of clear Yang to ascend， resulting in the lack of nourishment for the brain and the inability of turbid Yin to descend， which disturbs the clear orifices， thus causing vertigo. The core pathogenesis lies in the dysfunction of Qi movement， the disorder of body fluid distribution， and the imbalance between Yin and Yang. The compatibility of Xiao Chaihutang takes into account the methods of pungent medicinal materials opening and bitter medicinal materials descending， tonifying deficiency and purging excess， and regulating Qi movement. This prescription can regulate the pathological state of the mutual interference between clear Qi and turbid Qi from three aspects： regulating Qi movement throughout the body， harmonizing the distribution of body fluids， and coordinating Yin and Yang as well as the interior and exterior， thus preventing and treating vertigo. Modern research findings show that Xiao Chaihutang can improve hemodynamics to promote cerebral blood circulation and has anti-inflammation， immunomodulatory， and anti-tumor functions， which correspond to the therapeutic effects of Xiao Chaihutang under the theory of mutual interference between clear Qi and turbid Qi. The decoction exerts therapeutic effects on vertigo caused by hypertension， stroke， otitis media， Meniere’s disease， and brain tumor as well as benign paroxysmal positional vertigo. Further exploration of the theoretical connotation of mutual inference between clear Qi and turbid Qi and analysis of the pathogenesis of vertigo and the therapeutic effect of Xiao Chaihutang can better interpret the internal correlations among the three， thus providing new ideas for the syndrome differentiation and treatment of vertigo.

Osteoarthritis (OA) causes chronic pain that significantly impairs quality of life, with current treatments often proving insufficient and accompanied by adverse effects. Recent research has identified the dorsal root ganglion (DRG) and its resident macrophages as crucial mediators of chronic OA pain through neuroinflammation driven by macrophage polarization. We present a novel injectable thermo-sensitive hydrogel system, KAF@PLEL, designed to deliver an anti-inflammatory peptide (KAF) specifically to the DRG. This biodegradable hydrogel enables sustained KAF release, promoting the reprogramming of DRG macrophages from pro-inflammatory to anti-inflammatory phenotypes. Through comprehensive in vitro and in vivo studies, we evaluated the hydrogel's biocompatibility, effects on macrophage polarization, and therapeutic efficacy in chronic OA pain management. The system demonstrated significant capabilities in preserving macrophage mitochondrial function, suppressing neuroinflammation, alleviating chronic OA pain, reducing cartilage degradation, and improving motor function in OA rat models. The sustained-release properties of KAF@PLEL enabled prolonged therapeutic effects while minimizing systemic exposure and side effects. These findings suggest that KAF@PLEL represents a promising therapeutic approach for improving outcomes in OA patients through targeted, sustained treatment.

Objective:To improve the understanding of patients with diffuse large B-cell lymphoma (DLBCL) with pulmonary cryptococcosis.Methods:The clinical data of 1 DLBCL patient with pulmonary cryptococcosis in the Central Hospital of Fengxian District of Shanghai in May 2023 were retrospectively analyzed, and the relevant literatures were reviewed.Results:This 75-year-old female patient was asymptomatic after 2 cycles of R-CHOP chemotherapy. The high-resolution CT of lung showed that lung nodules were progressively enlarged. Antibacterial treatment was ineffective. Pulmonary cryptococcosis was confirmed by bronchoalveolar lavage fluid (BALF) targeted high-throughput sequencing (tNGS) and cryptococcus capsular antigen (CrAg) detection. The central nervous system was not involved. And the long-term adequate-dose fluconazole was prescribed for 6 months, and the treatment against lymphoma was given synchronously. The lung nodule lesions reduced after antifungal therapy for 1 month. The lung nodules disappeared after the follow-up of 6 months after completion of final chemotherapy. The evaluation of lymphoma indicated complete remission.Conclusions:Pulmonary cryptococcosis occurs insidiously and shows no specific symptoms; its imaging manifestations are variable and routine anti-infection is ineffective. Immunochemotherapy for lymphoma patients is a high-risk factor for cryptococcal infection. tNGS and CrAg testing for BALF are effective methods of the confirmed diagnosis. The early and long-term adequate-dose antifungal treatment is the key to preventing the recurrence or progression.

Moyamoya disease (MMD) is widely recognized as an important cause of ischemic stroke and hemorrhagic stroke. Cerebral revascularization is the standard treatment for preventing stroke recurrence in patients with MMD. However, cerebral hyperperfusion syndrome (CHS) is one of the main complications of cerebral revascularization in patients with MMD. This article reviews the predictive factors for postoperative CHS in patients with MMD undergoing cerebral revascularization.

Objective:To compare the clinical characteristics and magnetic resonance imaging(MRI)features of isolated infarction of the splenium of the corpus callosum and reversible splenial lesion syndrome(RESLES).Methods:Clinical and imaging findings of 12 patients with a clinical diagnosis of isolated infarction of splenium of the corpus callosum and 13 patients with RESLES from Deportment of Neurology in Beijing Geriatric Hospital between December 2018 and November 2022 and follow-up results were retrospectively analyzed.Results:The patients with isolated infarction of SCC were older than the patients with RESLES(age of patients with isolated infarction of SCC: 67.6±9.2, age of patients with RESLES: 23.2±17.8).All patients with infarction had one to three risk factors for cerebrovascular diseases.Both two groups showed hyperintense lesions on T2WI, fluid-attenuated inversion recovery(FLAIR)and diffusion-weighted imaging(DWI), and hyperintense lesions on T1WI and a low apparent diffusion coefficient(ADC).Most SCC infarctions occurred unilaterally(one case with bilateral lesions and 12 cases with unilateral lesions), with irregular dot-like or patchy lesions.Nine patients in the infarction group completed the follow-up, during which the lesions did not disappear on the T1WI, T2WI, FLAIR and ADC sequence.One patient in this group had a recurrent stroke.In the RESLES group, all lesions were located on the midline of SCC, with round, oval or boomerang-shaped lesions.All patients in the RESLES group completed the follow-up, during which lesions either shrank or disappeared.Conclusions:Infarction and RESLES can both result in SCC lesions.The existence of risk factors and imaging features about the locations of lesions, the morphology, and lesion changes during follow-up are helpful in the differential diagnosis.

Objective To investigate the initial dose and safety of intravenous infusion of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) for the displacement of cadmium. Methodsi) Efficacy test. The New Zealand male rabbits were randomly divided into model group, calcium disodium edetate (EDTA) group and GMDTC low-, medium- and high-dose groups after cadmium poisoning using 2.5 cadmium chloride dihydrate. Rabbits in EDTA group were intravenously injected with EDTA dipotassium at a dose of 93.5 mg/kg body weight, rabbits in the three doses groups were intravenously injected of GMDTC at doses of 12.0, 36.0, and 108.0 mg/kg body weight, respectively. The rabbits in the control group (separate set) and model group were intravenously injected with equal volumes of 0.9% sodium chloride solution, administered for five consecutive days per week for 1, 2, and 4 weeks. ii) Toxicity test. Specific pathogen free SD rats were randomly divided into solvent control group and low-, medium- and high-dose groups. In the acute toxicity test, the rats in the three-dose groups were intravenously injected of GMDTC at doses of 200.0, 800.0 and 3 000.0 mg/kg body weight, respectively. In the long-term toxicity test, the rats in the three-dose groups were intravenously injected GMDTC at doses of 100.0, 500.0 and 2 000.0 mg/kg body weight, respectively, once a day for four consecutive weeks, with a recovery period of four weeks. The rats in the solvent control group were given an equal volume 0.9% sodium chloride solution intravenously at the same time. The maximum tolerated dose (MTD) and no observable adverse effect level (NOAEL) were detected. Resultsi) In the one week treatment experiment, the 24 hours urinary cadmium levels of rabbits in the three doses groups were higher than those in the model group at the same time point (all P<0.05). In the two weeks treatment experiment, the 24 hours urinary cadmium levels of rabbits in medium-dose and high-dose groups at the three time points were higher than those in the model group at the same time point (all P<0.05). In the four weeks treatment experiment, the 24 hours urinary cadmium level on the 19th day of rabbits in the low-dose group was higher than that in the model group at the same time point (P<0.05), and the 24 hours urinary cadmium levels of rabbits in medium- and high-dose groups at the five time points were higher than those in the model group at the same time point (all P<0.05), except for the rabbits of fifth day of the medium-dose group. The kidney cadmium levels of rabbits in the low-dose group after four week of treatment and in the medium- and high-dose groups after one, two, and four weeks of treatment decreased compared with the model group (all P<0.05). No obvious adverse effects were observed during the treatment. ii) The MTD of GMDTC in rats administered intravenously in a single dose was 3 000.0 mg/kg body weight. During the period of intravenous infuseion with GMDTC for four consecutive weeks, the blood drug level reached the peak at the end of the first and last administrations (eight min), and no clinical adverse reactions were observed during this period of time, nor was there any apparent accumulation. The NOAEL for intravenous infusion of GMDTC for four consecutive weeks in rats was 500.0 mg/kg body weight. Conclusion The initial dose of the GMDTC injection in the cadmium poisoning rabbit was 36.0 mg/kg body weight, and the recommended initial dose for human is 480.0 mg/person. Intravenous infusion of GMDTC is characterized by rapid absorption, rapid elimination, and no accumulation.

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.