AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally, with a five-year overall survival rate alarmingly below 20%. Targeting autophagy, though a controversial therapeutic strategy, is extensively employed in clinical practice. Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy. Nevertheless, the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention. This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer. It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells. Notably, most autophagy-targeting drugs, primarily natural small molecules, have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer, as opposed to inhibiting protective autophagy. These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies, offering promising approaches to combat this disease.

Critical care emphasizes critical thinking, focuses on the triggers that lead to disease progression, and attaches great importance to early diagnosis of diseases and assessment of the compensatory capacity of vital organs. Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is relatively rare in the intensive care unit (ICU). Most cases occur within 10 weeks after delivery. Severe cases can be life-threatening. It characterized by microangiopathic hemolytic anemia, decreased platelet count (PLT), and acute kidney injury (AKI). Early clinical diagnosis is difficult due to its similarity to various disease manifestations. On January 28, 2024, a 26-year-old pregnant woman at 26⁺³ weeks gestation was transferred to the ICU 19 hours post-vaginal delivery due to abdominal pain, reduced urine output, decreased PLT, elevated D-dimer, tachycardia, increased respiratory rate and declined oxygenation. On the day of ICU admission, the critical care physician identified the causes that triggered the acute respiratory and circulatory events based on the "holistic and local" critical care thinking. The condition was stabilized rapidly by improving the capacity overload. In terms of etiological diagnosis, under the guidance of the "point and face" critical care thinking, starting from abnormality indicators including a decrease in hemoglobin (Hb) and PLT and elevated D-dimer and fibrin degradation product (FDP) without other abnormal coagulation indicators, the critical care physician ultimately determined the diagnosis direction of thrombotic microangiopathy (TMA) by delving deeply into the essence of the disease and formulating a laboratory examination plan in a reasonable and orderly manner. In terms of in-depth diagnosis, combining the disease development process, family history, and past history, applying the two-way falsification thinking of "forward and reverse" as well as "questioning and hypothesis", the diagnosis possibilities of preeclampsia, HELLP syndrome [including hemolysis (H), elevated liver function (EL) and low platelet count (LP)], thrombotic thrombocytopenic purpura (TTP), typical hemolytic uremic syndrome (HUS), and autoimmune inflammatory diseases inducing the condition was ruled out. The diagnosis of complement activation-induced P-aHUS was finally established for the patient, according to the positive result of the complement factor H (CFH). Active decision was made in the initial treatment. The plasma exchange was initiated early. "Small goals" were formulated in stages. The "small endpoints" were dynamically controlled in a goal-oriented manner to achieve continuous realization of the overall treatment effect through phased "small goals". On the 5th day of ICU treatment, the trend of microthrombosis in the patient was controlled, organ function damage was improved, and the patient was transferred out of the ICU. It is possible to reach a favorable clinical outcome for critically ill patients by applying a critical care mindset to quickly integrate diagnostic and therapeutic strategies, accurately identifying the triggers and causes that led to the progression of the disease, and using critical care medical techniques for early and effective intervention.
Humans ; Female ; Pregnancy ; Adult ; Atypical Hemolytic Uremic Syndrome/therapy* ; Intensive Care Units ; Pregnancy Complications, Hematologic/therapy* ; Critical Care

Objective: To investigate the potential efficacy and safety of Lutai Danshen Baishao granules (LDBG) for treating female melasma associated with kidney deficiency and blood stasis patterns. Methods: A randomized, double-blind, placebo-controlled trial was conducted at the Third Central Hospital of Tianjin, China from March to December 2023. A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days. Efficacy was assessed through measures such as the total melasma area, reduced melasma area, reduction rate of melasma area, melasma color score, Melasma Area and Severity Index (MASI) score, and traditional Chinese medicine (TCM) symptom score scale. Safety assessments included routine blood and biochemical tests. Results: Participants in both groups were aged 52–63 years, with no significant differences. After the 2-month intervention, the total melasma area decreased in both groups; however, a greater reduction was observed in the test group [462.50 mm2 (12.81%) vs. 100.00 mm2 (3.11%), P < .001]. Moreover, LDBG treatment significantly reduced the MASI and melasma color scores in the test group (P < .05). The total TCM symptom evaluation score significantly decreased (test group: 6.00 vs. placebo group: 7.00, P = .001), with significant relief in symptoms such as improvement in dark lips, nails, and waist soreness in the test group, compared with that in the placebo group (P < .05). Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group (P < .05). Conclusion LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.

AIM To explore the clinical effects of Jinfukang Oral Liquid combined with thymosin α1 on patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin.METHODS Seventy-five patients were randomly assigned into thymosin α1 group(15 cases)for 4-week administration,Jinfukang Oral Liquid group(30 cases)for 4-week administration,and combination group(30 cases)for 4-week administration.The changes in TCM clinical syndrome effects,immunity indices(CD3+T,Th,CTL,total NK,CD56dim CD16+NK,NKT,Treg,MDSC),lethality/inhibition ratios(CTL/Treg,total NK/Treg,NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC)and FACT-L scores were detected.RESULTS The Jinfukang Oral Liquid group and combination group demonstrated higher total effective rates than the thymosin α1 group(P＜0.05).After the treatment,the Jinfukang Oral Liquid group and combination group displayed increased NKT(P＜0.05)and decreased MDSC(P＜0.05),which were more obvious than those in the thymosin α1 group(P＜0.05),and higher NKT was observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group and combination group displayed increased lethality/inhibition ratios(P＜0.05),among which NKT/Treg,CTL/MDSC,total NK/MDSC,NKT/MDSC were higher than those in the thymosin α1 group(P＜0.05),and higher CTL/MDSC,NKT/MDSC were observable in the Jinfukang Oral Liquid group(P＜0.05);the Jinfukang Oral Liquid group(except for physiological status,society and family status)and combination group(except for society and family status)displayed increased FACT-L scores(P＜0.05).CONCLUSION For the patients with non-small cell lung cancer due to Dual Deficiency of Qi and Yin,Jinfukang Oral Liquid single use or combined with thymosin α1 can enhance peripheral blood immune surveillance,inhibit immune escape,restore the balanced state of tumor immune responses,and improve TCM syndromes and life quality.

Lung cancer exhibits the highest incidence and mortality rates among cancers globally,with a five-year overall survival rate alarmingly below 20％.Targeting autophagy,though a controversial therapeutic strategy,is extensively employed in clinical practice.Current research is actively pursuing various therapeutic strategies using small molecules to exploit the dual function of autophagy.Nevertheless,the pivotal question of enhancing or inhibiting autophagy in cancer therapy merits further attention.This review aims to provide a comprehensive overview of the mechanisms of autophagy in lung cancer.It also explores recent advances in targeting cytotoxic autophagy and inhibiting protective autophagy with small molecules to induce cell death in lung cancer cells.Notably,most autophagy-targeting drugs,primarily natural small molecules,have demonstrated that activating cytotoxic autophagy effectively induces cell death in lung cancer,as opposed to inhibiting protective autophagy.These insights contribute to identifying druggable targets and drug candidates for potential autophagy-related lung cancer therapies,offering promising approaches to combat this disease.

Objective To study the anti-inflammatory and analgesic effects of Ski protein overexpression on writing in mice induced by acetic acid.Methods Eight-week-old male ICR mice were administered 0.7%acetic acid solution(0.1 mL/10 g)to induce a writhing reaction.The mice were divided into sham,acetic acid,acetic acid+ibuprofen,acetic acid+ad-EGFP,acetic acid+ad-ski-1,acetic acid+ad-ski-2,and acetic acid+sulfasalazine groups(n=10 mice per group).The time to the first appearance of twisting and the number of twists within 15 min were recorded.Small intestine tissues were removed to identify the effect of adenovirus transfection and to detect protein expression levels of pro-inflammatory factors and pain biomarkers and protein expression of nuclear factor(NF)-κB p65 and its binding with Ski protein.Results Ski protein was successfully overexpressed in small intestine after intraperitoneal injection of Ad-ski adenovirus.Overexpressed Ski protein delayed the start and decreased the frequency of writhing,comparable to ibuprofen(P＞0.05).Groups in which ski protein was overexpressed showed significantly inhibited protein expression of pro-inflammatory factors and pain biomarkers compared with the acetic acid group(P＜0.05).Moreover,NF-κB p65 formed complexes with Ski.Conclusions Overexpression of Ski protein has anti-inflammatory and analgesic effects on acetic acid-induced inflammatory pain by inhibiting the expression of inflammatory factors and pain biomarkers,via regulation of the NF-κB signaling pathway.