Objective: The COVID-19 pandemic disrupted disease surveillance systems globally, leading to reduced notifications of other infectious diseases. This study aims to estimate the impact of the COVID-19 pandemic on the infectious disease surveillance system in Klang district, Selangor state, Malaysia. Methods: Data on notifiable diseases from 2014 to 2022 were sourced from the Klang District Health Office. The 11 diseases with more than 100 notifications each were included in the study. For these 11 diseases, a negative binomial regression model was used to explore the effect of the pandemic on case notifications and registrations by year, and a quasi-Poisson regression model was used to explore the changes by week. Results: The results showed a reduction in the number of notifications and registrations for all 11 diseases combined during the pandemic compared with previous years. Changes between expected and observed notifications by week were heterogeneous across the diseases. Discussion: These findings suggest that restrictive public health and social measures in Klang district may have impacted the transmission of other infectious diseases during the COVID-19 pandemic. The differential impact of the pandemic on disease notifications and reporting highlights the large ancillary effects of restrictive public health and social measures and the importance of building resilience into infectious disease surveillance systems.

ObjectiveTo investigate the effects of three traditional Chinese medicine formulas for nourishing kidney Yin on the occurrence of breast cancer， including Zuoguiwan（ZGW）， Liuwei Dihuangwan（LWDHW） and Erzhiwan（EZW）， and to explore their preventive mechanisms from the phagocytic function of macrophages. MethodsTen-month-old post-breeding female mice were randomly divided into the blank group， soy isoflavone group（0.13 g·kg^-1·d^-1， mixed with feed）， ZGW group（2.34 g·kg^-1·d^-1）， LWDHW group（0.56 g·kg^-1·d^-1）， and EZW group（4.68 g·kg^-1·d^-1）. The mice were palpated every 3 d until the age of 18 months， and those with detected lumps were confirmed for tumor development through hematoxylin-eosin（HE） staining， and the incidence of breast cancer in mice was calculated. A total of 40 SPF-grade female SD rats were randomly divided into the blank serum group（physiological saline）， ZGW drug-containing serum group（16.20 g·kg^-1·d^-1of ZGW）， LWDHW drug-containing serum group（3.89 g·kg^-1·d^-1 of LWDHW） and EZW drug-containing serum group（32.40 g·kg^-1·d^-1 of EZW）， each group was orally administered 3 times a day for 5 consecutive days. On the 5^th day， blood was collected from the abdominal aorta 1 h after the last gavage to prepare drug-containing serum. The effect of drug-containing serum with different concentrations on the viability of RAW264.7 cells was assessed by cell counting kit-8（CCK-8）. Taking 20% of drug-containing serum concentration as the research object， its effect on the expression levels of major histocompatibility complex-Ⅱ（MHC-Ⅱ）， CD80 and CD86 on the surface of RAW264.7 cells was detected by immunofluorescence（IF）， the phagocytic function of RAW264.7 cells was examined by flow cytometry， and the levels of interleukin-6（IL-6） and nitric oxide（NO） in RAW264.7 cells in the conditioned medium（CM） co culture system of 4T1 cells were detected by enzyme-linked immunosorbent assay（ELISA） and Griess assay. ResultsAfter prophylactic administration， the tumor incidence rates in the soy isoflavone group（4%）， ZGW group（4%）， LWDHW group（4%）， and EZW group（6%） were lower than that in the blank group（8%）. Compared with the blank serum group， the drug-containing serum of the three nourishing kidney Yin formulas could enhance the expression levels of MHC-Ⅱ， CD80 and CD86 on the surface of RAW264.7 cells， enhance phagocytic ability towards tumor cells， and reduce the content of IL-6 and increase the level of NO（P<0.05， P<0.01）. ConclusionThe three nourishing kidney Yin formulas can reduce the incidence of tumor in mice， the mechanism may be related to activating RAW264.7 cells， increasing their phagocytosis to breast cancer cells， and regulating the secretion of IL-6 and NO.

ObjectiveTo investigate the effect of astragaloside Ⅳ（AS-Ⅳ） on the proliferation of vascular smooth muscle cells（VSMCs） induced by angiotensin Ⅱ（Ang Ⅱ） based on solute carrier family 7 member 11/glutathione peroxidase 4（SLC7A11/GPX4） pathway. MethodsPrimary rat thoracic aortic VSMCs were cultured by tissue explant method， and the cell types were identified by immunofluorescence. Cell counting kit-8（CCK-8） was used to determine the optimal concentration and time of AS-Ⅳ after Ang Ⅱ stimulation. The experiment was divided into blank group， model group， AS-Ⅳ group（40 μmol·L^-1）， Erastin group（0.5 μmol·L^-1）， Erastin+AS-Ⅳ group（0.5 μmol·L^-1+40 μmol·L^-1）. The blank group was cultured in normal medium， the model group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1）， and each administration group was cultured in medium containing Ang Ⅱ（0.1 μmol·L^-1） and the corresponding doses of drug. CCK-8 and plate clone formation assay were used to detect the proliferation of cells in each group， Prussian blue staining was used to detect cell iron deposition， the content of reactive oxygen species（ROS） in cells was detected by fluorescence probe method， the content of malondialdehyde（MDA） was detected by thiobarbituric acid（TBA） method， and the protein levels of SLC7A11 and GPX4 in each group were detected by Western blot. ResultsPrimary rat thoracic aortic VSMCs were successfully cultured by tissue explant method， and immunofluorescence detection showed that positive expression of α-smooth muscle actin（α-SMA） and negative expression of vimentin in the cells， identifying them as VSMCs. The optimal concentration and time of AS-Ⅳ determined by CCK-8 were 40 μmol·L^-1 and 24 h， respectively. Pharmacodynamic studies showed that compared with the blank group， the cell proliferation in the model group increased， the iron deposition in the cells increased， the contents of ROS and MDA increased， and the expression levels of SLC7A11 and GPX4 proteins decreased（P<0.05， P<0.01）. Compared with the model group， the cell proliferation of the AS-Ⅳ group was inhibited， the iron deposition in the cells was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. While in the Erastin group， the cell proliferation was increased， the iron deposition was increased， ROS and MDA contents were increased， and the expression levels of SLC7A11 and GPX4 proteins were decreased（P<0.05， P<0.01）. Compared with the AS-Ⅳ group， Erastin+AS-Ⅳ group showed increased cell proliferation， increased iron deposition in cells， increased ROS and MDA contents， and decreased expression of SLC7A11 and GPX4 proteins（P<0.05）. Compared with the Erastin group， the cell proliferation in Erastin+AS-Ⅳ group was inhibited， the iron deposition was decreased， the contents of ROS and MDA were decreased， and the expression levels of SLC7A11 and GPX4 proteins were increased（P<0.05， P<0.01）. ConclusionAS-Ⅳ can inhibit ferroptosis by regulating the SLC7A11/GPX4 pathway， so as to weaken the proliferation of VSMCs， thus playing a role in the treatment of atherosclerosis.

AIM: To evaluate the efficacy of 3% diquafosol sodium ophthalmic solution in treating dry eye syndrome following cataract surgery and its impact on tear film stability.METHODS: This prospective clinical study was conducted at Xi'an Aier Eye Hospital, Northwest University from January 2021 to January 2024. A total of 124 patients(124 eyes)who underwent cataract phacoemulsification were enrolled and randomly assigned to either the study group(62 cases, 62 eyes)or the control group(62 cases, 62 eyes)using a random number table. The study group received 3% diquafosol sodium ophthalmic solution four times daily for 1 mo, while the control group was treated with sodium hyaluronate eye drops four times daily for 1 mo. Clinical efficacy, tear film breakup time(BUT), Schirmer I test(SⅠt), corneal fluorescein staining(FL)score, inflammatory factors [interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α)] levels in tears, and adverse reactions were compared between the two groups.RESULTS: After treatment, the effective rate was 93.5% in the study group and 87.1% in the control group, with no significant difference between the two groups(P>0.05). The study group showed significantly higher BUT, SⅠt values compared to the control group, while FL score, and inflammatory factor levels in tears were significantly lower at 1 mo after treatment(all P<0.05). The incidence of adverse reactions did not differ significantly between the two groups(P=0.198).CONCLUSION: The 3% diquafosol sodium ophthalmic solution significantly improves tear secretion and tear film stability in patients with dry eye syndrome after cataract surgery, effectively alleviating dry eye symptoms. It is a safe and effective treatment method.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

In January 2025， the European Society for Medical Oncology （ESMO） released the ESMO clinical practice guideline interim update on the management of biliary tract cancer as a supplementary update to Biliary tract cancer： ESMO clinical practice guideline for diagnosis， treatment and follow-up published in November 2022. This interim update mainly revises the latest evidence-based medical recommendations in the key fields of molecular diagnostics and clinical management since the release of the original guidelines， and it is not a comprehensive update of the entire document. This article summarizes and makes an excerpt of the new recommendations from this interim update.

BACKGROUND: Whether lipid-modifying drugs directly impact the outcome of sepsis remains uncertain. Therefore, systematic investigations are needed to explore the potential impact of lipid-related therapies on sepsis outcomes and to elucidate the underlying mechanisms involving circulating inflammatory cytokines, which may play critical roles in the pathogenesis of sepsis. This study aimed to utilize drug-target Mendelian randomization to assess the direct causal effects of genetically proxied lipid-modifying therapies on sepsis outcomes. METHODS: First, a two-sample Mendelian randomization study was conducted to validate the causal associations among high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and sepsis. A subsequent drug-target Mendelian randomization study assessed the direct causal effects of genetically proxied lipid-modifying therapies on the risk of sepsis, sepsis-related critical care admission, and sepsis-related death. The identified lipid-modifying drug targets were subsequently explored for direct causal relationships with 36 circulating inflammatory cytokines. Finally, enrichment analyses of the identified cytokines were conducted to explore the potential relationships of lipid-modifying drugs with the inflammatory response. RESULTS: Genetically proxied cholesteryl ester transfer protein (CETP) inhibitors were significantly associated with sepsis-related critical care admission (OR=0.84, 95% CI [0.74, 0.95], P=0.008,) and sepsis-related death (OR=0.68, 95% CI [0.52, 0.88], P=0.004). The genetically proxied CETP inhibitors were strongly associated with the levels of 15 circulating inflammatory cytokines. Enrichment analyses indicated that CETP inhibitors may modulate inflammatory cytokines and influence the inflammatory response pathway. CONCLUSION: This study supports a causal effect of genetically proxied CETP inhibitors in reducing the risk of sepsis-related critical care admission and death. These findings suggest that the underlying mechanism may involve the modulation of some circulating inflammatory cytokines, influencing the inflammatory response pathway.

Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.

ObjectiveTo investigate the mechanism of kidney-tonifying and liver-regulating cyclical therapy and its formula in regulating endometrial receptivity during the "implantation window" in rats with polycystic ovary syndrome （PCOS）. MethodsSix rats were randomly selected from 36 SPF SD female rats as the normal group， and the remaining rats were administered letrozole to induce a PCOS model. By using a random number method， the rats were divided into the following groups： normal group， model group， Xiaoyaosan group （11.97 g·kg^-1）， Sanzi Yangmo decoction group （28.35 g·kg^-1）， cyclical therapy group （11.97/28.35 g·kg^-1）， and aspirin group （8 × 10^-3 mg·kg^-1）. After 12 days of continuous administration by gavage （equivalent to three estrous cycles）， female and male rats were co-housed. On the fifth day of pregnancy， the number of blastocyst implantation in each group was counted. Hematoxylin-eosin （HE） staining was used to observe the pathological morphology of rat endometrial tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of estradiol （E₂） and progesterone （P） in rat serum. Western blot was used to detect the protein expression of vascular endothelial growth factor （VEGF）， progesterone receptor （PR）， estrogen receptor （ER）， androgen receptor （AR）， and integrin（ITG） αvβ3 in rat endometrial blood vessels. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-140-5 P， VEGF， vascular endothelial growth factor receptor 2 （VEGFR2）， PR， ER， AR， and ITGαvβ3 in rat endometrium. ResultsCompared with normal group， the estrous cycle of the rats in model group continued to be in the estrus interval and the estrous cycle lost regular changes. The endometrium was significantly thinner， the number of uterine glands and blood vessels were significantly reduced （P<0.01）， and the pregnancy rate was significantly reduced. Compared with the model group， each drug group restored the regular estrous cycle to varying degrees， and the endometrial thickness and the number of blood vessels were significantly improved （P<0.01）. The pregnancy rate of each drug group increased， and the effect of the cycle therapy group could reach the normal level. The results of molecular biology experiments showed that compared with the normal group， the levels of serum E₂ and P in the model group were significantly decreased （P<0.01）， the expression of VEGF， ER， PR and ITGαvβ3 protein was significantly decreased （P<0.05，P<0.01）， the expression of AR protein was significantly increased （P<0.01）， the expression of miR-140-5P and AR mRNA was significantly increased （P<0.01）， and the expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA was significantly decreased （P<0.01）. Compared with model group， the serum E₂ level in the Xiaoyaosan group was significantly increased （P<0.01）.The levels of E₂ and P in serum of rats in Sanzi Yangmo decoction group， cycle therapy group and aspirin group were significantly increased （P<0.01）. The expression of AR protein in each drug group was significantly decreased （P<0.01）. The expression of VEGF and ITGαvβ3 protein in Xiaoyaosan group was significantly increased （P<0.01）. The expression of VEGF， ER and PR protein in Sanzi Yangmo decoction group was increased to varying degrees （P<0.05，P<0.01）. The expression of VEGF， PR， ER and ITGαvβ3 protein in the cycle therapy group and the aspirin group increased to varying degrees （P<0.05，P<0.01）. The expression of miR-140-5P and AR mRNA in each drug group was significantly decreased （P<0.01）. The expression of VEGF， VEGFR2， ER， PR and ITGαvβ3 mRNA in each drug group increased to varying degrees （P<0.05，P<0.01）. Compared with Xiaoyaosan group and Sanzi Yangmo decoction group， the expression of miR-140-5P， VEGFR2， ER， PR， AR and ITGαvβ3 mRNA in the cycle therapy group were significantly different （P<0.05，P<0.01）. ConclusionThe kidney-tonifying and liver-regulating cyclical therapy may reduce the activity of miR-140-5P， target the upregulation of VEGF expression， mediate angiogenesis， and promote endometrial angiogenesis， thereby playing a synergistic role in improving endometrial receptivity in PCOS-induced infertility. Its efficacy in increasing pregnancy rates surpasses that of Xiaoyaosan or Sanzi Yangmo decoction used alone.