Comparison of Outcomes in Obese Patients after Total Knee Arthroplasty with Neutral or Mild Varus: A Retrospective Study with 8-Year Follow-Up.

OBJECTIVES: Residual varus after total knee arthroplasty (TKA) can affect functional outcomes, which may worsen in the presence of obesity. However, no studies were found to compare the outcomes of obese patients involving postoperative residual mild varus or neutral. The aim of this study was to compare postoperative complications and prosthesis survival, and functional outcomes for knees of obese patients with neutral or mild varus after TKA. METHODS: We retrospectively reviewed 188 consecutive obese patients (body mass index ≥30 kg/m2) at our hospital who underwent TKA due to varus knee osteoarthritis from January 2010 to December 2015. The mechanical hip-knee-ankle axis angle was measured in all patients at admission and discharge. Knee functions were retrospectively assessed based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society Knee Score (KS-KS), Knee Society Function Score (KS-FS), Forgotten Joint Score (FJS), and range of motion (ROM). Continuous data were compared between knees with neutral or mild varus alignment using analysis of Student's t test or variance or the Kruskal-Wallis test as appropriate. For multiple comparisons of outcomes, we used Bonferroni-Dunn method to adjust p-values. Categorical data were compared using the chi-squared test. RESULTS: Of the 156 knees in 137 obese patients who completed follow-up for a mean of 8.32 ± 1.47 years, 97 knees were corrected from varus to neutral and 54 knees were kept in mild residual varus. Patients with mild varus knees had significantly WOMAC (8.25 ± 8.637 vs. 14.97 ± 14.193, p = 0.009) and better FJS (86.03 ± 15.607 vs. 70.22 ± 30.031, p = 0.002). The two types of knees did not differ significantly in KS-KS, KS-FS, or ROM. Although one patient with a neutral knee had to undergo revision surgery, there was no significant difference between two groups. CONCLUSIONS: For obese patients with osteoarthritis, preservation of residual varus alignment after TKA can improve functional outcomes without compromising prosthesis survival.

Mitochondria-targeting peptide SS-31 attenuates ferroptosis via inhibition of the p38 MAPK signaling pathway in the hippocampus of epileptic rats.

Ferroptosis is a newly identified form of non-apoptotic regulated cell death (RCD) andplaysanimportantrole in epileptogenesis. The p38 mitogen-activated protein kinase (p38 MAPK) pathway has been confirmed to be involved in ferroptosis. The mitochondria-targeting antioxidant Elamipretide (SS-31) can reduce the generation of lipid peroxidation and the buildup of reactive oxygen species (ROS). Collectively, our present study was to decipher whether SS-31 inhibits ferroptosis via the p38 MAPK signaling pathway in the rat epilepsy model induced by pilocarpine (PILO).Adult male Wistar rats were randomly divided into four groups: control group (CON group), epilepsy group (EP group), SS-31 treatment group (SS group), and p38 MAPK inhibitor (SB203580) treatment group (SB group). Our results demonstrated that the rat hippocampal neurons after epilepsy were followed by accumulated iron and malondialdehyde (MDA) content, upregulated phosphorylated p38 MAPK protein (P-p38) and nuclear factor erythroid 2-related factor 2 (Nrf2) levels, reduced glutathione peroxidase 4 (Gpx4) content, and depleted glutathione (GSH) activity. Morphologically, mitochondrial ultrastructural damage under electron microscopy was manifested by a partial increase in outer membrane density, disappearance of mitochondrial cristae, and mitochondrial shrinkage. SS-31 and SB203580 treatment blocked the initiation and progression of ferroptosis in the hippocampus of epileptic rats via reducing the severity of epileptic seizures, reversing the expression of Gpx4, P-p38 and Nrf2, decreasing the levels of iron and MDA, as well as increasing the activity of GSH. To summarize, our findings proved that ferroptosis was coupled with the pathology of epilepsy, and SS-31 can inhibit PILO-induced seizures by preventing ferroptosis, which may be connected to the inhibition of p38 MAPK phosphorylation, highlighting the potential therapeutic value for targeting ferroptosis process in individuals with seizure-related diseases.

Corydecusines A-H, new phthalideisoquinoline hemicetal alkaloids from the bulbs of Corydalis decumbens inhibit Tau pathology by activating autophagy mediated by AMPK-ULK1 pathway.

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants. A summary of their ECD spectra was concluded and provided an insight for C-1, C-9, and C-7' absolute configuration assignment. These new compounds were evaluated to induce autophagy flux through flow cytometry analysis. Moreover, compounds 2 and 6 could significantly induce autophagy and inhibit Tau pathology by AMPK-ULK1 pathway activation, which provided an avenue for anti-AD lead compounds discovery.

Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives.

BACKGROUND: Stem cell therapy has shown great potential for treating diabetic foot (DF). AIM: To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades, with the aim of depicting the current global research landscape, identifying the most influential research hotspots, and providing insights for future research directions. METHODS: We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF. Bibliometric analysis was carried out using CiteSpace, VOSviewer, and R (4.3.1) to identify the most notable studies. RESULTS: A search was conducted to identify publications related to the use of stem cells for DF treatment. A total of 542 articles published from 2000 to 2023 were identified. The United States had published the most papers on this subject. In this field, Iran's Shahid Beheshti University Medical Sciences demonstrated the highest productivity. Furthermore, Dr. Bayat from the same university has been an outstanding researcher in this field. Stem Cell Research & Therapy is the journal with the highest number of publications in this field. The main keywords were "diabetic foot ulcers," "wound healing," and "angiogenesis." CONCLUSION: This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years. Current research findings suggested that the hotspots in this field include stem cell dressings, exosomes, wound healing, and adipose-derived stem cells. Future research should also focus on the clinical translation of stem cell therapies for DF.

Outcomes of culture-negative or -positive periprosthetic joint infections: A systematic review and meta-analysis.

OBJECTIVES: This study overviewed the current database of studies on periprosthetic joint infections (PJIs) to compare outcomes and antibiotic side effects in culture-negative or culture-positive PJIs and assess treatment options for culture-negative PJIs. PATIENTS AND METHODS: A systematic review and meta-analysis was undertaken using studies published before July 2022 in MEDLINE, EMBASE, and Cochrane Library. All studies comparing treatment of culture-negative or -positive PJIs were included. Afterward, the infection control rate, periprosthetic or spacer fracture, hip joint or spacer dislocation, and antibiotic side effects in different treatment methods of PJI were analyzed. RESULTS: Eleven studies involving 1,747 patients were included. Most studies clearly defined the infection control criteria: no pain or swelling, no wound drainage, normal serology, and normal radiographic findings. Patients were followed until treatment failure, death, or until the last clinical visit without evidence of treatment failure. The two types of PJIs did not differ significantly in infection control rates (culture-negative PJI 79.2% vs. culture-positive PJI 76.6%; odds ratio [OR]=1.20, 95% confidence interval [CI]: 0.84 to 1.70), either after all types of surgical treatment or after two-stage revision arthroplasty (OR=1.12, 95% CI: 0.72 to 1.75), single-stage revision arthroplasty (OR=0.51, 95% CI: 0.19 to 1.37), or debridement, antibiotics, and implant retention (OR=0.88, 95% CI: 0.50 to 1.54). Similarly, we did not find differences in periprosthetic or spacer fracture and hip joint or spacer dislocation. For culture-negative PJIs, the infection control rate was 85.2% after two-stage revision arthroplasty, 90.6% after single-stage revision arthroplasty, and 69.7% after debridement, antibiotics, and implant retention. Data pooled from three studies showed higher incidence of antibiotic side effects for culture-negative PJIs. CONCLUSION: The clinical outcomes of one-stage revision and two-stage revision are comparable. Therefore, both of them can be considered in surgical treatment for culture-negative PJIs. In addition, limited data showed a higher incidence of antibiotic side effects in culture-negative PJIs.

Effect of Anti-D titers in RhD-negative pregnant women on fetuses and newborns: A retrospective study.

BACKGROUND: Transplacental-derived anti-D IgG in RhD-negative pregnant women can trigger an immune response to Rh D-positive red cells in fetuses and newborns. We assessed the effect of anti-D titers in RhD-negative pregnant women on fetuses and newborns. METHODS: The clinical data of 142 singleton RhD-sensitized pregnancies were retrospectively collected. The pregnant women received routine prenatal care and the newborns had standard care. Based on the tertile categories of the pregnancies, the maximum titers of anti-D IgG in the pregnant women were divided into three groups ranging from low to high as follows: low-titer group (anti-D titer: 1:4-1:128, n = 57); medium-titer group (anti-D titer: 1:256-1:512, n = 50); and high-titer group (anti-D titer: 1:1024-1:4096, n = 35). RESULTS: The frequencies of major neonatal complications did not significantly differ among the three groups. The high-titer group had the highest frequency of pregnancies requiring intrauterine transfusion (IUT) and number of IUTs among the three groups. The high-titer group had a significantly higher frequency of newborns treated with top-up transfusion, number of top-up transfusions, frequency of newborns treated with exchange transfusion (ET), and number of ETs when compared to the low-titer group. CONCLUSION: Higher anti-D titers in RhD-negative pregnant women predict more severe fetal and neonatal hemolytic anemia. Increasing maternal anti-D titers results in an increased need for IUTs, and neonatal top-up transfusions and ETs. Methods for reducing titers of anti-D IgG in RhD-sensitized pregnant women warrants further investigation.

Al8 Cluster-Based Metal Halide Frameworks: Balancing Singlet-Triplet Excited States to Achieve White Light and Multicolor Luminescence.

Luminescent metal clusters have attracted great interest in current research; however, the design synthesis of Al clusters with color-tunable luminescence remains challenging. Herein, an [Al8 (OH)8 (NA)16 ] (Al8 , HNA = nicotinic acid) molecular cluster with dual luminescence properties of fluorescence and room-temperature phosphorescence (RTP) is synthesized by choosing HNA ligand as phosphor. Its prompt photoluminescence (PL) spectrum exhibits approximately white light emission at room temperature. Considering that halogen atoms can be used to regulate the RTP property by balancing the singlet and triplet excitons, different CdX2 (X- = Cl- , Br- , I- ) are introduced into the reactive system of the Al8 cluster, and three new Al8 cluster-based metal-organic frameworks, {[Al8 Cd3 Cl5 (OH)8 (NA)17 H2 O]·2HNA}n (CdCl2 -Al8 ), {[Al8 Cd4 Br7 (OH)8 (NA)16 CH3 CN]·NA·HNA}n (CdBr2 -Al8 ) and {[Al8 Cd8 I16 (OH)8 (NA)16 ]}n (CdI2 -Al8 ) are successfully obtained. They realize the color tunability from blue to yellow at room temperature. The origination of fluorescence and phosphorescence has also been illustrated by structure-property analysis and theoretical calculation. This work provides new insights into the design of multicolor luminescent metal cluster-based materials and develops advanced photo-functional materials for multicolor display, anti-counterfeiting, and encryption applications.

Effect of optional biometric parameters in the Kane formula on intraocular lens power calculation.

PURPOSE: To investigate the effect of the optional biometric parameters lens thickness (LT) and center corneal thickness (CCT) in the Kane formula on intraocular lens (IOL) power calculation. METHODS: A cross-sectional study included consecutive cataract patients who received uncomplicated cataract surgery with IOL implantation from May to September 2022 were enrolled. The ocular biometric parameters were obtained using IOLMaster 700 and then inputted into online Kane formula calculator. The IOL power was calculated for targeting emmetropia and compared between groups: not omitting (NO) group, omitting LT and CCT (OLC) group, omitting LT (OL) group and omitting CCT (OC) group. Further, according to the axial length (AL), anterior chamber depth (ACD), and mean keratometry (Km), the eyes were divided into three subgroups, respectively. RESULTS: 1005 eyes of 1005 consecutive patients were included. There was no significant difference in IOL power between NO group and OC group (P = 0.064), and the median absolute difference (MedAD) was 0.05D. The IOL power in NO group showed significant differences from OLC group and OL group respectively (P < 0.001), and both MedAD values were 0.18D. Among AL subgroups, MedAD ranged from 0.06D to 0.35D in short eyes. Among ACD subgroups, the above values ranged from 0.06D to 0.23D in shallow ACD subgroup. Among Km subgroups, these values ranged from 0.05D to 0.31D in steep Km subgroup. CONCLUSION: The optional biometric parameter CCT has no effect on the calculation results of the Kane formula, whereas the parameter LT has a great influence on the Kane formula results for the IOL power calculation in cataract patients with short AL, shallow ACD and steep Km.

External evaluation of the predictive performance of published population pharmacokinetic models of linezolid in adult patients.

OBJECTIVES: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. METHODS: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. RESULTS: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance. CONCLUSION: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.

Association between urinary neonicotinoid insecticide levels and dyslipidemia risk: A cross-sectional study in Chinese community-dwelling elderly.

Experimental evidence has demonstrated that neonicotinoids (NEOs) exposure can cause lipid accumulation and increased leptin levels. However, the relationship between NEOs exposure and dyslipidemia in humans remains unclear, and the interactive effects of NEOs and their characteristic metabolites on dyslipidemia remain unknown. We detected 14 NEOs and their metabolites in urine samples of 500 individuals (236 and 264 with and without dyslipidemia, respectively) randomly selected from the baseline of the Yinchuan community-dwelling elderly cohort (Ningxia, China). The NEOs and their metabolites were widely detected in urine (87.2-99.6 %) samples, and the median levels ranged within 0.06-0.55 µg/g creatinine. The positive associations and dose-dependent relationships of thiacloprid, imidacloprid-olefin, and imidacloprid-equivalent total with dyslipidemia were validated using restricted cubic spline analysis. Mixture models revealed a positive association between the NEOs mixture and dyslipidemia risk, with urine desnitro-imidacloprid ranked as the top contributor. The Bayesian Kernel Machine Regression models showed that the NEOs mixtures were associated with increased dyslipidemia when the chemical mixtures were ≥ 25th percentile compared to their medians, and desnitro-imidacloprid and imidacloprid-olefin were the major contributors to the combined effect. Given the widespread use of NEOs and the dyslipidemia pandemic, further investigations are urgently needed to confirm our findings and elucidate the underlying mechanisms.

Effect of fucoidan on gut microbiota and its clinical efficacy in Helicobacter pylori eradication: A randomized controlled trial.

OBJECTIVE: To assess the clinical efficacy of fucoidan-assisted standard quadruple therapy (SQT) in Helicobacter pylori (H. pylori) eradication and the improvement of gut microbiota. METHODS: An open-label randomized controlled trial was conducted at the Affiliated Hospital of Qingdao University in Shandong Province, China. Ninety patients who tested positive for H. pylori were randomized to the standard quadruple therapy (SQT) group (SQ), SQT + fucoidan combination group (SF), and fucoidan + sequential SQT group (FS), respectively. Stool samples were collected for gut microbiota composition at baseline and after treatment. RESULTS: After H. pylori eradication, the relative abundances of most conditional pathogens in the SQ decreased, while those of several beneficial bacteria increased or decreased (P < 0.05). In FS, the abundances of most beneficial bacteria increased gradually from baseline to week 12, while those of the conditional pathogens decreased (P < 0.05). The abundance of Bifidobacterium had a decreasing trend in SQ, but remained unchanged in SF and increased in FS (P < 0.05). The abundances of most beneficial bacteria were significantly higher in FS than in SQ and SF (P < 0.05). Addition of fucoidan enhanced symptom improvement during H. pylori eradication compared with SQT alone. CONCLUSIONS: Fucoidan considerably improved gut dysbiosis during SQT for H. pylori eradication. Gut microbiota can be maintained by the addition of fucoidan before eradication therapy with SQT rather than by concomitant addition with therapy. Fucoidan-assisted SQT could relieve gastrointestinal symptoms during H. pylori eradication.

Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy.

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.

A 2D flexible cobalt-MOF: reversible solid-state structural transformation, two-step and gate-opening adsorption behaviours, and selective adsorption of C2H2 over CO2 and CH4.

A new 2D flexible cobalt(II) framework (Co-MOF) exhibits a reversible solid-state structural transformation upon guest molecule removal/uptake. After activation, Co-MOF-α with 1D porous channels transformed into Co-MOF-ß (0D voids) accompanied by a shift in metal and carboxylate coordination modes, the rotation of organic linkers and the contraction of interstitial spaces. Gas adsorption experiments reveal that Co-MOF-ß exhibits a two-step CO2 adsorption isotherm and close-to-open (type F-IV) isotherms for C2H2, C2H4 and C2H6 at 195 K. Moreover, it shows typical type I adsorption isotherms for the above gases and the selective uptake of C2H2 over CH4 and CO2 at room temperature.

Cured HCV patients with suboptimal hepatitis B vaccine response exhibit high self-reactive immune signatures.

BACKGROUND AND RATIONALE: Chronic HCV infection induces lasting effects on the immune system despite viral clearance. It is unclear whether certain immune alterations are associated with vaccine responses in cured HCV patients. APPROACH: Thirteen cured HCV patients received the standard 3-dose hepatitis B vaccine and were followed up at the 0, 1st, 6th, and 7th months (M0, M1, M6, and M7) after the first dose of vaccination. Thirty-three-color and 26-color spectral flow cytometry panels were used for high-dimensional immunophenotyping of the T-cell and B-cell subsets, respectively. RESULTS: Compared to the healthy controls (HC), 17 of 43 (39.5%) immune cell subsets showed abnormal frequencies in cured HCV patients. Patients with cured HCV were further divided into high responders (HR, n = 6) and nonresponders (NR1, n = 7) based on the levels of hepatitis B surface antibodies at M1. Alterations in cell populations were more significant in NR1. Moreover, we found that high levels of self-reactive immune signatures, including Tregs, TD/CD8, IgD-only memory B, and autoantibodies, were associated with suboptimal hepatitis B vaccine responses. CONCLUSIONS: Our data suggest that cured HCV patients exhibit persistent perturbations in the adaptive immune system, among which highly self-reactive immune signatures may contribute to a suboptimal hepatitis B vaccine response.

The Role of G3BP1 Gene Mediates P38 MAPK/JNK Pathway in Testicular Spermatogenic Dysfunction Caused by Cyfluthrin.

In recent years, male infertility has received global attention and seriously affected the quality of human fertility, and pyrethroids (type II pyrethroids), as recognized environmental endocrine disruptors, may threaten male reproductive health. Therefore, in this study, we established an in vivo model for the development of testicular and germ cell toxicity induced by cyfluthrin and explored the role and mechanism of the G3BP1 gene-mediated P38 MAPK/JNK pathway in testicular and germ cell damage caused by cyfluthrin to find early and sensitive indicators and new therapeutic targets for the development of testicular damage. Firstly, 40 male Wistar rats (about 260 g) were divided into a control group (corn oil), low dose group (6.25 mg/kg), middle dose group (12.5 mg/kg) and high dose group (25 mg/kg). The rats were anesthetized and executed after 28 days of poisoning on alternate days. Then, HE staining, transmission electron microscopy, ELISA, q-PCR, Western blot, immunohistochemistry, double-immunofluorescence and TUNEL were used to observe the pathology, androgen levels, oxidative damage and altered expression of the key factors of the G3BP1 and MAPK pathways in rat testes. The results showed that, compared with the control group, the testicular tissue and spermatocytes were superficially damaged with an increasing dose of cyfluthrin; furthermore, it could interfere with the normal secretion of the hypothalamic-pituitary-gonadal axis (serum GnRH, FSH, T and LH levels) and cause hypergonadal dysfunction. A dose-dependent increase in MDA and a dose-dependent decrease in T-AOC indicated that the oxidative-antioxidative homeostatic balance was disrupted. The Western blot and qPCR analysis revealed that G3BP1, p-JNK1/2/3, P38 MAPK, p-ERK, COX1 and COX4 proteins and mRNA expression were decreased, and p-JNK1/2/3, p-P38MAPK, caspase 3/8/9 proteins and mRNA expression were significantly increased. The double-immunofluorescence and immunohistochemistry results showed that the protein expression of G3BP1 decreased with an increasing dose of staining, while the expression of JNK1/2/3 and P38 MAPK were increased significantly. The positive expressions of G3BP1 were mainly located in the testicular germinal epithelium and germ cell layer, and the positive expressions of JNK1/2/3 were mainly located in the testicular germinal epithelium and sperm cells, while the positive expressions of P38 MAPK were located in all levels of the germ cells and spermatozoa. Our results demonstrated that exposure to cyfluthrin caused testicular and spermatocyte damage in rats, which could cause pathomorphology, altered androgen levels and a decreased antioxidant capacity. When the intracellular antioxidant capacity was impaired, G3BP1 expression and activity were inhibited, causing activation of the P38 MAPK/JNK pathway and activation of the intracellular apoptotic pathway, which, in turn, led to germ cell apoptosis.

Variations of soil quality in the southern Qinghai-Tibet Plateau during 1980s to 2020s.

Climate warming and thawing of permafrost in the Qinghai-Tibet Plateau have resulted in soil erosion and the decline of soil quality. Determining the decadal variation of soil quality in the Qinghai-Tibet Plateau is the basis for scientific understanding of soil resources and the key to vegetation restoration and ecological reconstruction. In this study, we used eight indicators (including soil organic matter, total nitrogen, and total phosphorus) to eva-luate soil quality of montane coniferous forest zone (Tibet's natural geographical division zone Ⅱ) and montane shrubby steppe zone (zone Ⅳ) by calculating soil quality index (SQI) in the southern Qinghai-Tibet Plateau in the 1980s and 2020s. Variation partitioning (VPA) was used to examine the drivers for the heterogeneity of the spatial-temporal distribution of soil quality. The results showed that soil quality in each natural zone showed a downward trend in the past 40 years, with SQI of zone Ⅱ decreasing from 0.505 to 0.484 and that of zone Ⅳ decreasing from 0.458 to 0.425. The spatial distribution of soil nutrients and quality was heterogeneous, while soil nutrient conditions and quality in zone Ⅱ were better than those in zone Ⅳ in different periods. The VPA results indicated that the interaction of climate change, land degradation, and vegetation differences was the major cause of temporal variation in soil quality. Differences in climate and vegetation could better explain the spatial variation of SQI.

Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer.

Currently, for ovarian cancer, which has the highest mortality rate among all gynecological cancers, the standard treatment protocol is initial tumor cytoreductive surgery followed by platinum-based combination chemotherapy. Although the survival rate after standard treatment has improved, the therapeutic effect of traditional chemotherapy is very limited due to problems such as resistance to platinum-based drugs and recurrence. With the advent of the precision medicine era, molecular targeted therapy has gradually entered clinicians' view, and individualized precision therapy has been realized, surpassing the limitations of traditional therapy. The detection of genetic mutations affecting treatment, especially breast cancer susceptibility gene (BRCA) mutations and mutations of other homologous recombination repair defect (HRD) genes, can guide the targeted drug treatment of patients, effectively improve the treatment effect and achieve a better patient prognosis. This article reviews different sites and pathways of targeted therapy, including angiogenesis, cell cycle and DNA repair, and immune and metabolic pathways, and the latest research progress from preclinical and clinical trials related to ovarian cancer therapy.

Immune cells and immune cell-targeted therapy in chronic pancreatitis.

In recent years, studies have attempted to understand the immune cells and mechanisms underlying the pathogenesis of chronic pancreatitis (CP) by constructing a model of CP. Based on these studies, the innate immune response is a key factor in disease pathogenesis and inflammation severity. Novel mechanisms of crosstalk between immune and non-immune pancreatic cells, such as pancreatic stellate cells (PSC), have also been explored. Immune cells, immune responses, and signaling pathways in CP are important factors in the development and progression of pancreatitis. Based on these mechanisms, targeted therapy may provide a feasible scheme to stop or reverse the progression of the disease in the future and provide a new direction for the treatment of CP. This review summarizes the recent advances in research on immune mechanisms in CP and the new advances in treatment based on these mechanisms.