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.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Purpose: Approximately 50%-74% of patients with metastatic human epidermal growth factor receptor 2 (HER2)–positive breast cancer do not respond to trastuzumab, with 75% of treated patients experiencing disease progression within a year. The combination of pyrotinib and capecitabine has showed efficacy in these patients. This study evaluates the efficacy and safety of pyrotinib combined with metronomic vinorelbine for trastuzumab-pretreated HER2-positive advanced breast cancer patients. Materials and Methods: In this phase 2 trial, patients aged 18-75 years with HER2-positive advanced breast cancer who had previously failed trastuzumab treatment were enrolled to receive pyrotinib 400 mg daily in combination with vinorelbine 40mg thrice weekly. The primary endpoint was progression-free survival (PFS), while secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: From October 21, 2019, to January 21, 2022, 36 patients were enrolled and received at least one dose of study treatment. At the cutoff date, 20 experienced disease progression or death. With a median follow-up duration of 35 months, the median PFS was 13.5 months (95% confidence interval [CI], 8.3 to 18.5). With all patients evaluated, an ORR of 38.9% (95% CI, 23.1 to 56.5) and a DCR of 83.3% (95% CI, 67.2 to 93.6) were achieved. The median OS was not reached. Grade 3 adverse events (AEs) were observed in 17 patients, with diarrhea being the most common (27.8%), followed by vomiting (8.3%) and stomachache (5.6%). There were no grade 4/5 AEs. Conclusion Pyrotinib combined with metronomic vinorelbine showed promising efficacy and an acceptable safety profile in HER2-positive advanced breast cancer patients after trastuzumab failure.

ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside （Hyp） on lipopolysaccharide （LPS）-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L^-1 LPS or immersed in 1 g·L^-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25， 50， and 100 mg·L^-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate， malformation rate， body length， and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses， and macrophage migration was observed by fluorescence microscopy. Additionally， the mRNA levels of inflammation-related genes， including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， chemokine C-C motif ligand 2 （CCL2）， chemokine C-X3-C motif receptor 1 （CX3CR1）， chemokine C-C motif receptor 2 （CCR2）， and genes associated with the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-kappa B （NF-κB） signaling pathway， were measured by Real-time quantitative polymerase chain reaction（Real-time PCR）. ResultsCompared with the pure water injection group， the model group exhibited increased mortality， malformation rates and yolk sac area ratio （P0.01）， reduced body length （P0.01）， increased total swimming distance and high-speed swimming duration （P0.01）， and up-regulated mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.01）. Hyp at low， medium and high doses， as well as aspirin， reduced the mortality and malformation rates （P0.05，P0.01）， increased the body length （P0.05，P0.01）， decreased the yolk sac area ratio （P0.01）， reduced the high-speed swimming duration （P0.01）， and down-regulated the mRNA levels of TLR4， MyD88， NF-κB， IL-1β， IL-6， CCL2， CX3CR1， and CCR2 （P0.05，P0.01） compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish， thereby exerting the anti-inflammatory effect.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.013.].

Objective To investigate the electrophysiological characteristics and clinical significance of unilateral tinnitus with normal hearing threshold.Methods A total of 34 patients with normal hearing but unilateral tinnitus admitted to our department from May 2022 to February 2023 were recruited as the study subjects.Pure tone hearing threshold detection,distortion product otoacoustic emission(DPOAE),auditory brainstem response(ABR)detection and extended high-frequency pure tone audiometry were performed on both ears(affected side and healthy side)of every patient.The data of the affected side group and those of healthy side group were compared.Results The Ⅰ-wave latency of ABR was significantly shorter(1.60 vs 1.73 ms,P=0.018),and its amplitude was obviously decreased(0.19 vs 0.23 μV,P=0.003)in the affected side group when compared with the healthy side group.In the affected group(34 ears),there were 18 ears(52.94％)having amplitude of wave Ⅲ greater than that of wave Ⅴ,while in the healthy group,no such difference in the amplitude between wave Ⅲ and wave Ⅴ was observed.There was statistical significance between the 2 groups(Chi-square=24.480,P＜0.001).In the 12.5,14.0,16.0,18.0 and 20.0 kHz conditions,the average hearing threshold of extended high-frequency audiometry was all significantly higher in the affected side group than the healthy group(P＜0.05).Conclusion For subjective tinnitus patients with normal hearing threshold,ABR examination is helpful in preliminarily determining whether there are hidden functional changes in the auditory pathway.Decreased Ⅰ-wave amplitude,shortened Ⅰ-wave latency,and wave Ⅲ amplitude greater than wave Ⅴ amplitude can be used as objective reference indicators.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.

OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group， postpartum depression group， and low-dose and high-dose groups of E. ulmoides （1.34， 2.68 g/kg， calculated by crude drug）， with 10 rats in each group. Except for the normal group， the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy； at the same time of modeling， the administration groups were given relevant medicine intragastrically， while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test， Morris water maze test and sucrose preference test. Additionally， the levels of corticosterone （CORT） in serum， corticotropin releasing factor （CRF） and urocortin （UCN） in hypothalamus， and adrenocorticotropic hormone （ACTH） in hypophysis were detected； meanwhile， the protein expressions of CRF receptor 1 （CRFR1）， CRFR2， and voltage-dependent anion channel 1 （VDAC1） in hippocampal tissue were measured； the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined， and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group， the high-dose group of E. ulmoides showed improvements in appetite， mental state， and hair color in rats； their body weight had increased； the scores of vertical movement， horizontal movement and self-sorting significantly increased； from the 2ed to 4th day avoidance latency significantly shortened， and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目（No.82204789） significantly increased/prolonged （P＜0.05）； the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum （P＜0.05）； the levels of CRF， UCN， ACTH and CORT， phagocytic rate， protein expressions of CRFR2 and VDAC1， and the proportion of apoptosis cells in hippocampal tissue were decreased significantly （P＜0.05）； the proportion of JC-1 high potential cells significantly increased （P＜0.05）， and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis， decreasing the expression of CRFR2， thereby inhibiting the expression of VDAC1， and decreasing the apoptosis of neuronal cells.